Aurobindo Pharma Limited

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Aurobindo Pharma Limited Drugs

Memantine Hydrochloride...

Memantine Hydrochloride

The recommended starting dose of memantine hydrochloride tablets is 5 mg once daily. The dose should be increased in 5 mg increments to 10 mg/day (5 mg twice daily), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg twice daily). The minimum recommended interval between dose increases is one week. The dosage shown to be effective in controlled clinical trials is 20 mg/day.Memantine hydrochloride tablets can be taken with or without food. If a patient misses a single dose of memantine hydrochloride tablets, that patient should not double up on the next dose. The next dose should be taken as scheduled. If a patient fails to take memantine hydrochloride tablets for several days, dosing may need to be resumed at lower doses and retitrated as described above.Special Populations Renal Impairment A target dose of 5 mg twice daily is recommended in patients with severe renal impairment (creatinine clearance of 5 to 29 mL/min based on the Cockroft-Gault equation). Hepatic Impairment Memantine hydrochloride tablets should be administered with caution to patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].
Gemfibrozil

Gemfibrozil

The recommended dose for adults is 1200 mg administered in two divided doses 30 minutes before the morning and evening meals (see CLINICAL PHARMACOLOGY). OVERDOSAGE There have been reported cases of overdosage with gemfibrozil. In one case, a 7-year-old child recovered after ingesting up to 9 grams of gemfibrozil. Symptoms reported with overdosage were abdominal cramps, abnormal liver function tests, diarrhea, increased CPK, joint and muscle pain, nausea and vomiting. Symptomatic supportive measures should be taken, should an overdose occur.
Signature Care Acid Con...

Signature Care Acid Control

If significant diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING box).Concomitant administration of food does not adversely affect the absorption of clindamycin palmitate hydrochloride contained in clindamycin palmitate hydrochloride for oral solution (Pediatric).Serious infections:

8 to 12 mg/kg/day (4 to 6 mg/lb/day) divided into 3 or 4 equal doses.Severe infections:

13 to 16 mg/kg/day (6.5 to 8 mg/lb/day) divided into 3 or 4 equal doses.More severe infections:

17 to 25 mg/kg/day (8.5 to 12.5 mg/lb/day) divided into 3 or 4 equal doses.In pediatric patients weighing 10 kg or less, ½ teaspoon (37.5 mg) three times a day should be considered the minimum recommended dose.Serious infections due to anaerobic bacteria are usually treated with clindamycin injection. However, in clinically appropriate circumstances, the physician may elect to initiate treatment or continue treatment with clindamycin palmitate hydrochloride for oral solution (Pediatric). NOTE: In cases of β-hemolytic streptococcal infections, treatment should be continued for at least 10 days. Reconstitution Instructions When reconstituted with water as follows, each 5 mL (teaspoonful) of solution contains clindamycin palmitate hydrochloride equivalent to 75 mg clindamycin.Reconstitute bottles of 100 mL with 75 mL of water. Add a large portion of the water and shake vigorously; add the remainder of the water and shake until the solution is uniform.Storage Conditions Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]Do NOT refrigerate the reconstituted solution; when chilled, the solution may thicken and be difficult to pour. The solution is stable for 2 weeks at room temperature.
Pure Petroleum Aloe Wit...

Pure Petroleum Aloe With Vitamin E Oil

2.1 Hypertension

Dosage must be individualized. The usual starting dose of telmisartan tablets is 40 mg once a day. Blood pressure response is dose-related over the range of 20 to 80 mg [see Clinical Studies (14.1)]. Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. When additional blood pressure reduction beyond that achieved with 80 mg telmisartan tablets are required, a diuretic may be added.No initial dosage adjustment is necessary for elderly patients or patients with renal impairment, including those on hemodialysis. Patients on dialysis may develop orthostatic hypotension; their blood pressure should be closely monitored. Telmisartan tablets may be administered with other antihypertensive agents.Telmisartan tablets may be administered with or without food.
Omeprazole

Omeprazole

Omeprazole delayed-release capsules should be taken before eating. In the clinical trials, antacids were used concomitantly with omeprazole.Patients should be informed that the omeprazole delayed-release capsule should be swallowed whole.For patients unable to swallow an intact capsule, alternative administration options are available [see Dosage and Administration (2.8)].

2.1 Short-Term Treatment of Active Duodenal Ulcer

The recommended adult oral dose of omeprazole delayed-release capsules is 20 mg once daily. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.

2.2 H. pylori Eradication for the Reduction of the Risk of Duodenal Ulcer Recurrence

Triple Therapy (omeprazole/clarithromycin/amoxicillin)— The recommended adult oral regimen is omeprazole delayed-release capsules 20 mg plus clarithromycin 500 mg plus amoxicillin 1000 mg each given twice daily for 10 days. In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole delayed-release capsules 20 mg once daily is recommended for ulcer healing and symptom relief. Dual Therapy (omeprazole/clarithromycin) — The recommended adult oral regimen is omeprazole delayed-release capsules 40 mg once daily plus clarithromycin 500 mg three times daily for 14 days. In patients with an ulcer present at the time of initiation of therapy, an additional 14 days of omeprazole delayed-release capsules 20 mg once daily is recommended for ulcer healing and symptom relief.

2.3 Gastric Ulcer

The recommended adult oral dose is 40 mg once daily for 4 to 8 weeks.

2.4 Gastroesophageal Reflux Disease (GERD)

The recommended adult oral dose for the treatment of patients with symptomatic GERD and no esophageal lesions is 20 mg daily for up to 4 weeks. The recommended adult oral dose for the treatment of patients with erosive esophagitis and accompanying symptoms due to GERD is 20 mg daily for 4 to 8 weeks.

2.5 Maintenance of Healing of Erosive Esophagitis

The recommended adult oral dose is 20 mg daily. Controlled studies do not extend beyond 12 months [see Clinical Studies (14.4)].

2.6 Pathological Hypersecretory Conditions

The dosage of omeprazole delayed-release capsules in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 120 mg three times daily have been administered. Daily dosages of greater than 80 mg should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously with omeprazole delayed-release capsules for more than 5 years.

2.7 Pediatric Patients

For the treatment of GERD and maintenance of healing of erosive esophagitis, the recommended daily dose for pediatric patients 2 to 16 years of age is as follows:
Patient Weight Omeprazole Daily Dose 10 < 20 kg 10 mg ≥ 20 kg 20 mg
On a per kg basis, the doses of omeprazole required to heal erosive esophagitis in pediatric patients are greater than those for adults.Alternative administrative options can be used for pediatric patients unable to swallow an intact capsule [see Dosage and Administration (2.8)].

2.8 Alternative Administration Options

Omeprazole is available as a delayed-release capsule.For patients who have difficulty swallowing capsules, the contents of an omeprazole delayed-release capsule can be added to applesauce.One tablespoon of applesauce should be added to an empty bowl and the capsule should be opened. All of the pellets inside the capsule should be carefully emptied on the applesauce. The pellets should be mixed with the applesauce and then swallowed immediately with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The pellets should not be chewed or crushed. The pellets/applesauce mixture should not be stored for future use.
Raloxifene Hydrochlorid...

Raloxifene Hydrochloride

2.1 Recommended Dosing

The recommended dosage is one 60 mg raloxifene hydrochloride tablet daily, which may be administered any time of day without regard to meals [see Clinical Pharmacology (12.3)].

For the indications in risk of invasive breast cancer the optimum duration of treatment is not known [see Clinical Studies (14.3, 14.4)].

2.2 Recommendations for Calcium and Vitamin D Supplementation

For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Total daily intake of calcium above 1500 mg has not demonstrated additional bone benefits while daily intake above 2000 mg has been associated with increased risk of adverse effects, including hypercalcemia and kidney stones. The recommended intake of vitamin D is 400 to 800 IU daily. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home bound, or chronically ill) may need additional vitamin D supplements. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.
Entecavir

Entecavir

2.1 Timing of Administration

Entecavir tablets should be administered on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal).

2.2 Recommended Dosage in Adults

Compensated Liver Disease The recommended dose of entecavir tablets for chronic hepatitis B virus infection in nucleoside-inhibitor-treatment-naïve adults and adolescents 16 years of age and older is 0.5 mg once daily.The recommended dose of entecavir tablets in adults and adolescents (at least 16 years of age) with a history of hepatitis B viremia while receiving lamivudine or known lamivudine or telbivudine resistance substitutions rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L is 1 mg once daily. Decompensated Liver Disease The recommended dose of entecavir tablets for chronic hepatitis B virus infection in adults with decompensated liver disease is 1 mg once daily.

2.3 Recommended Dosage in Pediatric Patients

Pediatric use information is approved for Bristol-Myers Squibb Company’s entecavir tablets. However, due to Bristol-Myers Squibb Company’s marketing exclusivity rights, this drug product is not labeled with that information.

2.4 Renal Impairment

In adult subjects with renal impairment, the apparent oral clearance of entecavir decreased as creatinine clearance decreased [see Clinical Pharmacology (12.3)]. Dosage adjustment is recommended for patients with creatinine clearance less than 50 mL/min, including patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), as shown in Table 2. The once-daily dosing regimens are preferred.
b If administered on a hemodialysis day, administer entecavir tablets after the hemodialysis session. Table 2: Recommended Dosage of Entecavir Tablets in Adult Patients with Renal Impairment Creatinine Clearance (mL/min) Usual Dose (0.5 mg) Lamivudine-Refractory or Decompensated Liver Disease (1 mg) 50 or greater 0.5 mg once daily 1 mg once daily 30 to less than 50 0.5 mg every 48 hours 0.5 mg once dailyOR 1 mg every 48 hours 10 to less than 30 0.5 mg every 72 hours 1 mg every 72 hours Less than 10Hemodialysisb or CAPD 0.5 mg every 7 days 1 mg every 7 days

Pediatric use information is approved for Bristol-Myers Squibb Company’s entecavir tablets. However, due to Bristol-Myers Squibb Company’s marketing exclusivity rights, this drug product is not labeled with that information.

2.5 Hepatic Impairment

No dosage adjustment is necessary for patients with hepatic impairment.

2.6 Duration of Therapy

The optimal duration of treatment with entecavir tablets for patients with chronic hepatitis B virus infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown.
Atracurium Besylate

Atracurium Besylate

To avoid distress to the patient, atracurium should not be administered before unconsciousness has been induced. Atracurium should not be mixed in the same syringe, or administered simultaneously through the same needle, with alkaline solutions (e.g., barbiturate solutions).Atracurium besylate should be administered intravenously. DO NOT GIVE ATRACURIUM BESYLATE BY INTRAMUSCULAR ADMINISTRATION. Intramuscular administration of atracurium besylate may result in tissue irritation and there are no clinical data to support this route of administration.As with other neuromuscular blocking agents, the use of a peripheral nerve stimulator will permit the most advantageous use of atracurium besylate, minimizing the possibility of overdosage or underdosage, and assist in the evaluation of recovery. Bolus Doses for Intubation and Maintenance of Neuromuscular Block Adults An atracurium besylate dose of 0.4 to 0.5 mg/kg (1.7 to 2.2 times the ED95), given as an intravenous bolus injection, is the recommended initial dose for most patients. With this dose, good or excellent conditions for nonemergency intubation can be expected in 2 to 2.5 minutes in most patients, with maximum neuromuscular block achieved approximately 3 to 5 minutes after injection. Clinically required neuromuscular block generally lasts 20 to 35 minutes under balanced anesthesia. Under balanced anesthesia, recovery to 25% of control is achieved approximately 35 to 45 minutes after injection, and recovery is usually 95% complete approximately 60 minutes after injection.Atracurium is potentiated by isoflurane or enflurane anesthesia. The same initial atracurium besylate dose of 0.4 to 0.5 mg/kg may be used for intubation prior to administration of these inhalation agents; however, if atracurium is first administered under steady-state of isoflurane or enflurane, the initial atracurium besylate dose should be reduced by approximately one-third, i.e., to 0.25 to 0.35 mg/kg, to adjust for the potentiating effects of these anesthetic agents. With halothane, which has only a marginal (approximately 20%) potentiating effect on atracurium, smaller dosage reductions may be considered.Atracurium besylate doses of 0.08 to 0.1 mg/kg are recommended for maintenance of neuromuscular block during prolonged surgical procedures. The first maintenance dose will generally be required 20 to 45 minutes after the initial atracurium besylate injection, but the need for maintenance doses should be determined by clinical criteria. Because atracurium lacks cumulative effects, maintenance doses may be administered at relatively regular intervals for each patient, ranging approximately from 15 to 25 minutes under balanced anesthesia, slightly longer under isoflurane or enflurane. Higher atracurium doses (up to 0.2 mg/kg) permit maintenance dosing at longer intervals. Pediatric Patients No atracurium dosage adjustments are required for pediatric patients two years of age or older. An atracurium besylate dose of 0.3 to 0.4 mg/kg is recommended as the initial dose for infants (1 month to 2 years of age) under halothane anesthesia. Maintenance doses may be required with slightly greater frequency in infants and children than in adults. Special Considerations An initial atracurium besylate dose of 0.3 to 0.4 mg/kg, given slowly or in divided doses over one minute, is recommended for adults, children, or infants with significant cardiovascular disease and for adults, children, or infants with any history (e.g., severe anaphylactoid reactions or asthma) suggesting a greater risk of histamine release.Dosage reductions must be considered also in patients with neuromuscular disease, severe electrolyte disorders, or carcinomatosis in which potentiation of neuromuscular block or difficulties with reversal have been demonstrated. There has been no clinical experience with atracurium in these patients, and no specific dosage adjustments can be recommended. No atracurium dosage adjustments are required for patients with renal disease.An initial atracurium besylate dose of 0.3 to 0.4 mg/kg is recommended for adults following the use of succinylcholine for intubation under balanced anesthesia. Further reductions may be desirable with the use of potent inhalation anesthetics. The patient should be permitted to recover from the effects of succinylcholine prior to atracurium administration. Insufficient data are available for recommendation of a specific initial atracurium dose for administration following the use of succinylcholine in children and infants.Use by Continuous Infusion Infusion in the Operating Room (OR) After administration of a recommended initial bolus dose of atracurium besylate injection (0.3 to 0.5 mg/kg), a diluted solution of atracurium besylate can be administered by continuous infusion to adults and pediatric patients aged 2 or more years for maintenance of neuromuscular block during extended surgical procedures.Infusion of atracurium should be individualized for each patient. The rate of administration should be adjusted according to the patient’s response as determined by peripheral nerve stimulation. Accurate dosing is best achieved using a precision infusion device.Infusion of atracurium should be initiated only after early evidence of spontaneous recovery from the bolus dose. An initial infusion rate of 9 to 10 mcg/kg/min may be required to rapidly counteract the spontaneous recovery of neuromuscular function. Thereafter, a rate of 5 to 9 mcg/kg/min should be adequate to maintain continuous neuromuscular block in the range of 89% to 99% in most pediatric and adult patients under balanced anesthesia. Occasional patients may require infusion rates as low as 2 mcg/kg/min or as high as 15 mcg/kg/min.The neuromuscular blocking effect of atracurium administered by infusion is potentiated by enflurane or isoflurane and, to a lesser extent, by halothane. Reduction in the infusion rate of atracurium should, therefore, be considered for patients receiving inhalation anesthesia. The rate of atracurium infusion should be reduced by approximately one-third in the presence of steady-state enflurane or isoflurane anesthesia; smaller reductions should be considered in the presence of halothane.In patients undergoing cardiopulmonary bypass with induced hypothermia, the rate of infusion of atracurium required to maintain adequate surgical relaxation during hypothermia (25° to 28°C) has been shown to be approximately half the rate required during normothermia.Spontaneous recovery from neuromuscular block following discontinuation of atracurium infusion may be expected to proceed at a rate comparable to that following administration of a single bolus dose. Infusion in the Intensive Care Unit (ICU) The principles for infusion of atracurium in the OR are also applicable to use in the ICU.An infusion rate of 11 to 13 mcg/kg/min (range: 4.5 to 29.5) should provide adequate neuromuscular block in adult patients in an ICU. Limited information suggests that infusion rates required for pediatric patients in the ICU may be higher than in adult patients. There may be wide interpatient variability in dosage requirements and these requirements may increase or decrease with time (see PRECAUTIONS: Long-Term Use in Intensive Care Unit (ICU)). Following recovery from neuromuscular block, readministration of a bolus dose may be necessary to quickly re-establish neuromuscular block prior to reinstitution of the infusion. Infusion Rate Tables The amount of infusion solution required per minute will depend upon the concentration of atracurium in the infusion solution, the desired dose of atracurium, and the patient’s weight. The following tables provide guidelines for delivery, in mL/hr (equivalent to microdrops/min when 60 microdrops = 1 mL), of atracurium solutions in concentrations of 0.2 mg/mL (20 mg in 100 mL) or 0.5 mg/mL (50 mg in 100 mL) with an infusion pump or a gravity flow device.
Table 3: Atracurium Besylate Infusion Rates for a Concentration of 0.2 mg/mL Patient Weight (kg) Drug Delivery Rate (mcg/kg/min) 5 6 7 8 9 10 11 12 13 Infusion Delivery Rate (mL/hr) 30 45 54 63 72 81 90 99 108 117 35 53 63 74 84 95 105 116 126 137 40 60 72 84 96 108 120 132 144 156 45 68 81 95 108 122 135 149 162 176 50 75 90 105 120 135 150 165 180 195 55 83 99 116 132 149 165 182 198 215 60 90 108 126 144 162 180 198 216 234 65 98 117 137 156 176 195 215 234 254 70 105 126 147 168 189 210 231 252 273 75 113 135 158 180 203 225 248 270 293 80 120 144 168 192 216 240 264 288 312 90 135 162 189 216 243 270 297 324 351 100 150 180 210 240 270 300 330 360 390 Table 4: Atracurium Besylate Infusion Rates for a Concentration of 0.5 mg/mL Patient Weight (kg) Drug Delivery Rate (mcg/kg/min) 5 6 7 8 9 10 11 12 13 Infusion Delivery Rate (mL/hr) 30 18 22 25 29 32 36 40 43 47 35 21 25 29 34 38 42 46 50 55 40 24 29 34 38 43 48 53 58 62 45 27 32 38 43 49 54 59 65 70 50 30 36 42 48 54 60 66 72 78 55 33 40 46 53 59 66 73 79 86 60 36 43 50 58 65 72 79 86 94 65 39 47 55 62 70 78 86 94 101 70 42 50 59 67 76 84 92 101 109 75 45 54 63 72 81 90 99 108 117 80 48 58 67 77 86 96 106 115 125 90 54 65 76 86 97 108 119 130 140 100 60 72 84 96 108 120 132 144 156
Compatibility and Admixtures Atracurium besylate infusion solutions may be prepared by admixing atracurium besylate injection with an appropriate diluent such as 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection. Infusion solutions should be used within 24 hours of preparation. Unused solutions should be discarded. Solutions containing 0.2 mg/mL or 0.5 mg/mL atracurium besylate in the above diluents may be stored either under refrigeration or at room temperature for 24 hours without significant loss of potency. Care should be taken during admixture to prevent inadvertent contamination. Visually inspect prior to administration.Spontaneous degradation of atracurium besylate has been demonstrated to occur more rapidly in Lactated Ringer’s solution than in 0.9% sodium chloride solution. Therefore, it is recommended that Lactated Ringer’s Injection not be used as a diluent in preparing solutions of atracurium besylate injection for infusion.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Atracurium Besylate

Atracurium Besylate

To avoid distress to the patient, atracurium should not be administered before unconsciousness has been induced. Atracurium should not be mixed in the same syringe, or administered simultaneously through the same needle, with alkaline solutions (e.g., barbiturate solutions).Atracurium besylate should be administered intravenously. DO NOT GIVE ATRACURIUM BESYLATE BY INTRAMUSCULAR ADMINISTRATION. Intramuscular administration of atracurium besylate may result in tissue irritation and there are no clinical data to support this route of administration.As with other neuromuscular blocking agents, the use of a peripheral nerve stimulator will permit the most advantageous use of atracurium besylate, minimizing the possibility of overdosage or underdosage, and assist in the evaluation of recovery. Bolus Doses for Intubation and Maintenance of Neuromuscular Block Adults An atracurium besylate dose of 0.4 to 0.5 mg/kg (1.7 to 2.2 times the ED95), given as an intravenous bolus injection, is the recommended initial dose for most patients. With this dose, good or excellent conditions for nonemergency intubation can be expected in 2 to 2.5 minutes in most patients, with maximum neuromuscular block achieved approximately 3 to 5 minutes after injection. Clinically required neuromuscular block generally lasts 20 to 35 minutes under balanced anesthesia. Under balanced anesthesia, recovery to 25% of control is achieved approximately 35 to 45 minutes after injection, and recovery is usually 95% complete approximately 60 minutes after injection.Atracurium is potentiated by isoflurane or enflurane anesthesia. The same initial atracurium besylate dose of 0.4 to 0.5 mg/kg may be used for intubation prior to administration of these inhalation agents; however, if atracurium is first administered under steady-state of isoflurane or enflurane, the initial atracurium besylate dose should be reduced by approximately one-third, i.e., to 0.25 to 0.35 mg/kg, to adjust for the potentiating effects of these anesthetic agents. With halothane, which has only a marginal (approximately 20%) potentiating effect on atracurium, smaller dosage reductions may be considered.Atracurium besylate doses of 0.08 to 0.1 mg/kg are recommended for maintenance of neuromuscular block during prolonged surgical procedures. The first maintenance dose will generally be required 20 to 45 minutes after the initial atracurium besylate injection, but the need for maintenance doses should be determined by clinical criteria. Because atracurium lacks cumulative effects, maintenance doses may be administered at relatively regular intervals for each patient, ranging approximately from 15 to 25 minutes under balanced anesthesia, slightly longer under isoflurane or enflurane. Higher atracurium doses (up to 0.2 mg/kg) permit maintenance dosing at longer intervals. Pediatric Patients No atracurium dosage adjustments are required for pediatric patients two years of age or older. An atracurium besylate dose of 0.3 to 0.4 mg/kg is recommended as the initial dose for infants (1 month to 2 years of age) under halothane anesthesia. Maintenance doses may be required with slightly greater frequency in infants and children than in adults. Special Considerations An initial atracurium besylate dose of 0.3 to 0.4 mg/kg, given slowly or in divided doses over one minute, is recommended for adults, children, or infants with significant cardiovascular disease and for adults, children, or infants with any history (e.g., severe anaphylactoid reactions or asthma) suggesting a greater risk of histamine release.Dosage reductions must be considered also in patients with neuromuscular disease, severe electrolyte disorders, or carcinomatosis in which potentiation of neuromuscular block or difficulties with reversal have been demonstrated. There has been no clinical experience with atracurium in these patients, and no specific dosage adjustments can be recommended. No atracurium dosage adjustments are required for patients with renal disease.An initial atracurium besylate dose of 0.3 to 0.4 mg/kg is recommended for adults following the use of succinylcholine for intubation under balanced anesthesia. Further reductions may be desirable with the use of potent inhalation anesthetics. The patient should be permitted to recover from the effects of succinylcholine prior to atracurium administration. Insufficient data are available for recommendation of a specific initial atracurium dose for administration following the use of succinylcholine in children and infants.Use by Continuous Infusion Infusion in the Operating Room (OR) After administration of a recommended initial bolus dose of atracurium besylate injection (0.3 to 0.5 mg/kg), a diluted solution of atracurium besylate can be administered by continuous infusion to adults and pediatric patients aged 2 or more years for maintenance of neuromuscular block during extended surgical procedures.Infusion of atracurium should be individualized for each patient. The rate of administration should be adjusted according to the patient’s response as determined by peripheral nerve stimulation. Accurate dosing is best achieved using a precision infusion device.Infusion of atracurium should be initiated only after early evidence of spontaneous recovery from the bolus dose. An initial infusion rate of 9 to 10 mcg/kg/min may be required to rapidly counteract the spontaneous recovery of neuromuscular function. Thereafter, a rate of 5 to 9 mcg/kg/min should be adequate to maintain continuous neuromuscular block in the range of 89% to 99% in most pediatric and adult patients under balanced anesthesia. Occasional patients may require infusion rates as low as 2 mcg/kg/min or as high as 15 mcg/kg/min.The neuromuscular blocking effect of atracurium administered by infusion is potentiated by enflurane or isoflurane and, to a lesser extent, by halothane. Reduction in the infusion rate of atracurium should, therefore, be considered for patients receiving inhalation anesthesia. The rate of atracurium infusion should be reduced by approximately one-third in the presence of steady-state enflurane or isoflurane anesthesia; smaller reductions should be considered in the presence of halothane.In patients undergoing cardiopulmonary bypass with induced hypothermia, the rate of infusion of atracurium required to maintain adequate surgical relaxation during hypothermia (25° to 28°C) has been shown to be approximately half the rate required during normothermia.Spontaneous recovery from neuromuscular block following discontinuation of atracurium infusion may be expected to proceed at a rate comparable to that following administration of a single bolus dose. Infusion in the Intensive Care Unit (ICU) The principles for infusion of atracurium in the OR are also applicable to use in the ICU.An infusion rate of 11 to 13 mcg/kg/min (range: 4.5 to 29.5) should provide adequate neuromuscular block in adult patients in an ICU. Limited information suggests that infusion rates required for pediatric patients in the ICU may be higher than in adult patients. There may be wide interpatient variability in dosage requirements and these requirements may increase or decrease with time (see PRECAUTIONS: Long-Term Use in Intensive Care Unit (ICU)). Following recovery from neuromuscular block, readministration of a bolus dose may be necessary to quickly re-establish neuromuscular block prior to reinstitution of the infusion. Infusion Rate Tables The amount of infusion solution required per minute will depend upon the concentration of atracurium in the infusion solution, the desired dose of atracurium, and the patient’s weight. The following tables provide guidelines for delivery, in mL/hr (equivalent to microdrops/min when 60 microdrops = 1 mL), of atracurium solutions in concentrations of 0.2 mg/mL (20 mg in 100 mL) or 0.5 mg/mL (50 mg in 100 mL) with an infusion pump or a gravity flow device.
Table 3: Atracurium Besylate Infusion Rates for a Concentration of 0.2 mg/mL Patient Weight (kg) Drug Delivery Rate (mcg/kg/min) 5 6 7 8 9 10 11 12 13 Infusion Delivery Rate (mL/hr) 30 45 54 63 72 81 90 99 108 117 35 53 63 74 84 95 105 116 126 137 40 60 72 84 96 108 120 132 144 156 45 68 81 95 108 122 135 149 162 176 50 75 90 105 120 135 150 165 180 195 55 83 99 116 132 149 165 182 198 215 60 90 108 126 144 162 180 198 216 234 65 98 117 137 156 176 195 215 234 254 70 105 126 147 168 189 210 231 252 273 75 113 135 158 180 203 225 248 270 293 80 120 144 168 192 216 240 264 288 312 90 135 162 189 216 243 270 297 324 351 100 150 180 210 240 270 300 330 360 390 Table 4: Atracurium Besylate Infusion Rates for a Concentration of 0.5 mg/mL Patient Weight (kg) Drug Delivery Rate (mcg/kg/min) 5 6 7 8 9 10 11 12 13 Infusion Delivery Rate (mL/hr) 30 18 22 25 29 32 36 40 43 47 35 21 25 29 34 38 42 46 50 55 40 24 29 34 38 43 48 53 58 62 45 27 32 38 43 49 54 59 65 70 50 30 36 42 48 54 60 66 72 78 55 33 40 46 53 59 66 73 79 86 60 36 43 50 58 65 72 79 86 94 65 39 47 55 62 70 78 86 94 101 70 42 50 59 67 76 84 92 101 109 75 45 54 63 72 81 90 99 108 117 80 48 58 67 77 86 96 106 115 125 90 54 65 76 86 97 108 119 130 140 100 60 72 84 96 108 120 132 144 156
Compatibility and Admixtures Atracurium besylate infusion solutions may be prepared by admixing atracurium besylate injection with an appropriate diluent such as 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection. Infusion solutions should be used within 24 hours of preparation. Unused solutions should be discarded. Solutions containing 0.2 mg/mL or 0.5 mg/mL atracurium besylate in the above diluents may be stored either under refrigeration or at room temperature for 24 hours without significant loss of potency. Care should be taken during admixture to prevent inadvertent contamination. Visually inspect prior to administration.Spontaneous degradation of atracurium besylate has been demonstrated to occur more rapidly in Lactated Ringer’s solution than in 0.9% sodium chloride solution. Therefore, it is recommended that Lactated Ringer’s Injection not be used as a diluent in preparing solutions of atracurium besylate injection for infusion.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Flecainide Acetate

Flecainide Acetate

For patients with sustained VT, no matter what their cardiac status, flecainide acetate tablets, like other antiarrhythmics, should be initiated in-hospital with rhythm monitoring. Flecainide has a long half-life (12 to 27 hours in patients). Steady-state plasma levels, in patients with normal renal and hepatic function, may not be achieved until the patient has received 3 to 5 days of therapy at a given dose. Therefore, increases in dosage should be made no more frequently than once every four days, since during the first 2 to 3 days of therapy the optimal effect of a given dose may not be achieved.For patients with PSVT and patients with PAF the recommended starting dose is 50 mg every 12 hours. Flecainide acetate tablets dose may be increased in increments of 50 mg bid every four days until efficacy is achieved. For PAF patients, a substantial increase in efficacy without a substantial increase in discontinuations for adverse experiences may be achieved by increasing the flecainide acetate tablets dose from 50 to 100 mg bid. The maximum recommended dose for patients with paroxysmal supraventricular arrhythmias is 300 mg/day.For sustained VT the recommended starting dose is 100 mg every 12 hours. This dose may be increased in increments of 50 mg bid every four days until efficacy is achieved. Most patients with sustained VT do not require more than 150 mg every 12 hours (300 mg/day) and the maximum dose recommended is 400 mg/day.In patients with sustained VT, use of higher initial doses and more rapid dosage adjustments have resulted in an increased incidence of proarrhythmic events and CHF, particularly during the first few days of dosing (see WARNINGS). Therefore, a loading dose is not recommended.Intravenous lidocaine has been used occasionally with flecainide acetate tablets while awaiting the therapeutic effect of flecainide acetate tablets. No adverse drug interactions were apparent. However, no formal studies have been performed to demonstrate the usefulness of this regimen.An occasional patient not adequately controlled by (or intolerant to) a dose given at 12-hour intervals may be dosed at eight-hour intervals.Once adequate control of the arrhythmia has been achieved, it may be possible in some patients to reduce the dose as necessary to minimize side effects or effects on conduction. In such patients, efficacy at the lower dose should be evaluated.Flecainide acetate tablets should be used cautiously in patients with a history of CHF or myocardial dysfunction (see WARNINGS).Any use of flecainide acetate tablets in children should be directly supervised by a cardiologist skilled in the treatment of arrhythmias in children. Because of the evolving nature of information in this area, specialized literature should be consulted. Under six months of age, the initial starting dose of flecainide acetate tablets in children is approximately 50 mg/m2 body surface area daily, divided into two or three equally spaced doses. Over six months of age, the initial starting dose may be increased to 100 mg/m2 per day. The maximum recommended dose is 200 mg/m2 per day. This dose should not be exceeded. In some children on higher doses, despite previously low plasma levels, the level has increased rapidly to far above therapeutic values while taking the same dose. Small changes in dose may also lead to disproportionate increases in plasma levels. Plasma trough (less than one hour pre-dose) flecainide levels and electrocardiograms should be obtained at presumed steady state (after at least five doses) either after initiation or change in flecainide acetate tablets dose, whether the dose was increased for lack of effectiveness, or increased growth of the patient. For the first year on therapy, whenever the patient is seen for reasons of clinical follow-up, it is suggested that a 12-lead electrocardiogram and plasma trough flecainide level are obtained. The usual therapeutic level of flecainide in children is 200 to 500 ng/mL. In some cases, levels as high as 800 ng/mL may be required for control.In patients with severe renal impairment (creatinine clearance of 35 mL/min/1.73 square meters or less), the initial dosage should be 100 mg once daily (or 50 mg bid); when used in such patients, frequent plasma level monitoring is required to guide dosage adjustments (see Plasma Level Monitoring). In patients with less severe renal disease, the initial dosage should be 100 mg every 12 hours; plasma level monitoring may also be useful in these patients during dosage adjustment. In both groups of patients, dosage increases should be made very cautiously when plasma levels have plateaued (after more than four days), observing the patient closely for signs of adverse cardiac effects or other toxicity. It should be borne in mind that in these patients it may take longer than four days before a new steady-state plasma level is reached following a dosage change.Based on theoretical considerations, rather than experimental data, the following suggestion is made: when transferring patients from another antiarrhythmic drug to flecainide acetate tablets allow at least two to four plasma half-lives to elapse for the drug being discontinued before starting flecainide acetate tablets at the usual dosage. In patients where withdrawal of a previous antiarrhythmic agent is likely to produce life-threatening arrhythmias, the physician should consider hospitalizing the patient.When flecainide is given in the presence of amiodarone, reduce the usual flecainide dose by 50% and monitor the patient closely for adverse effects.Plasma level monitoring is strongly recommended to guide dosage with such combination therapy (see below).

Plasma Level Monitoring

The large majority of patients successfully treated with flecainide acetate tablets were found to have trough plasma levels between 0.2 and 1 mcg/mL. The probability of adverse experiences, especially cardiac, may increase with higher trough plasma levels, especially when these exceed 1 mcg/mL. Periodic monitoring of trough plasma levels may be useful in patient management. Plasma level monitoring is required in patients with severe renal failure or severe hepatic disease, since elimination of flecainide from plasma may be markedly slower. Monitoring of plasma levels is strongly recommended in patients on concurrent amiodarone therapy and may also be helpful in patients with CHF and in patients with moderate renal disease.
Entacapone

Entacapone

The recommended dose of entacapone is one 200 mg tablet administered concomitantly with each levodopa and carbidopa dose to a maximum of 8 times daily (200 mg x 8 = 1,600 mg per day). Clinical experience with daily doses above 1,600 mg is limited.Entacapone tablets should always be administered in association with levodopa and carbidopa. Entacapone has no antiparkinsonian effect of its own.In clinical studies, the majority of patients required a decrease in daily levodopa dose if their daily dose of levodopa had been greater than or equal to 800 mg or if patients had moderate or severe dyskinesia before beginning treatment.To optimize an individual patient’s response, reductions in daily levodopa dose or extending the interval between doses may be necessary. In clinical studies, the average reduction in daily levodopa dose was about 25% in those patients requiring a levodopa dose reduction. (More than 58% of patients with levodopa doses above 800 mg daily required such a reduction.)Entacapone tablets can be combined with both the immediate and sustained-release formulations of levodopa and carbidopa.Entacapone tablets may be taken with or without food (see CLINICAL PHARMACOLOGY). Patients With Impaired Hepatic Function Patients with hepatic impairment should be treated with caution. The AUC and Cmax of entacapone approximately doubled in patients with documented liver disease, compared to controls. However, these studies were conducted with single-dose entacapone without levodopa and dopa decarboxylase inhibitor coadministration, and therefore the effects of liver disease on the kinetics of chronically administered entacapone have not been evaluated (see CLINICAL PHARMACOLOGY, Pharmacokinetics of Entacapone). Withdrawing Patients from Entacapone Tablets Rapid withdrawal or abrupt reduction in the entacapone tablets dose could lead to emergence of signs and symptoms of Parkinson’s disease (see CLINICAL PHARMACOLOGY, Clinical Studies), and may lead to hyperpyrexia and confusion, a symptom complex resembling NMS (see PRECAUTIONS, Other Events Reported With Dopaminergic Therapy). This syndrome should be considered in the differential diagnosis for any patient who develops a high fever or severe rigidity. If a decision is made to discontinue treatment with entacapone tablets, patients should be monitored closely and other dopaminergic treatments should be adjusted as needed. Although tapering entacapone tablets has not been systematically evaluated, it seems prudent to withdraw patients slowly if the decision to discontinue treatment is made.
Extended Phenytoin Sodi...

Extended Phenytoin Sodium

Serum concentrations should be monitored in changing from extended phenytoin sodium capsules to Prompt Phenytoin Sodium Capsules, USP, and from the sodium salt to the free acid form. Extended phenytoin sodium capsules are formulated with the sodium salt of phenytoin. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa. General Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum level is usually 10 to 20 mcg/mL. With recommended dosage, a period of seven to ten days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than seven to ten days. Adult Dosage Divided Daily DosagePatients who have received no previous treatment may be started on one 100 mg extended phenytoin sodium capsule three times daily and the dosage then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be one capsule three to four times a day. An increase up to two capsules three times a day may be made, if necessary. Once-a-Day DosageIn adults, if seizure control is established with divided doses of three 100 mg extended phenytoin sodium capsules daily, once-a-day dosage with 300 mg of extended phenytoin sodium capsules may be considered. Studies comparing divided doses of 300 mg with a single daily dose of this quantity indicated absorption, peak plasma levels, biologic half-life, difference between peak and minimum values, and urinary recovery were equivalent. Once-a-day dosage offers a convenience to the individual patient or to nursing personnel for institutionalized patients and is intended to be used only for patients requiring this amount of drug daily. A major problem in motivating noncompliant patients may also be lessened when the patient can take this drug once a day. However, patients should be cautioned not to miss a dose, inadvertently. Only extended phenytoin sodium capsules are recommended for once-a-day dosing. Inherent differences in dissolution characteristics and resultant absorption rates of phenytoin due to different manufacturing procedures and/or dosage forms preclude such recommendation for other phenytoin products. When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out. Loading DoseSome authorities have advocated use of an oral loading dose of phenytoin in adults who require rapid steady-state serum levels and where intravenous administration is not desirable. This dosing regimen should be reserved for patients in a clinic or hospital setting where phenytoin serum levels can be closely monitored. Patients with a history of renal or liver disease should not receive the oral loading regimen. Initially, one gram of extended phenytoin sodium capsules are divided into three doses (400 mg, 300 mg, 300 mg) and administered at two-hour intervals. Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations.

Dosing in Special Populations Patients with Renal or Hepatic Disease Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution. Unbound phenytoin concentrations may be more useful in these patient populations. Elderly Patients Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required. Pediatric Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years old and adolescents may require the minimum adult dose (300 mg/day).
Metronidazole

Metronidazole

TrichomoniasisIn the FemaleOne-day treatment − two grams of metronidazole tablets, given either as a single dose or in two divided doses of one gram each, given in the same day. Seven-day course of treatment − 250 mg three times daily for seven consecutive days. There is some indication from controlled comparative studies that cure rates as determined by vaginal smears and signs and symptoms, may be higher after a seven-day course of treatment than after a one-day treatment regimen.The dosage regimen should be individualized. Single-dose treatment can assure compliance, especially if administered under supervision, in those patients who cannot be relied on to continue the seven-day regimen. A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain appropriate treatment. Further, some patients may tolerate one treatment regimen better than the other.Pregnant patients should not be treated during the first trimester (see CONTRAINDICATIONS). In pregnant patients for whom alternative treatment has been inadequate, the one-day course of therapy should not be used, as it results in higher serum levels which can reach the fetal circulation (see PRECAUTIONS, Pregnancy).When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and that the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leukocyte counts should be made before and after re-treatment.In the MaleTreatment should be individualized as it is for the female.AmebiasisAdultsFor acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days. For amebic liver abscess: 500 mg or 750 mg orally three times daily for 5 to 10 days.Pediatric patients35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days. Anaerobic Bacterial Infections In the treatment of most serious anaerobic infections, intravenous metronidazole is usually administered initially.The usual adult oral dosage is 7.5 mg/kg every six hours (approximately 500 mg for a 70 kg adult). A maximum of 4 g should not be exceeded during a 24-hour period.The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.Dosage AdjustmentsPatients with Severe Hepatic ImpairmentFor patients with severe hepatic impairment (Child-Pugh C), the dose of metronidazole tablets should be reduced by 50% (see CLINICAL PHARMACOLOGY and PRECAUTIONS).Patients Undergoing HemodialysisHemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation. The clearance of metronidazole will depend on the type of dialysis membrane used, the duration of the dialysis session, and other factors. If the administration of metronidazole cannot be separated from the hemodialysis session, supplementation of metronidazole dosage following the hemodialysis session should be considered, depending on the patient’s clinical situation (see CLINICAL PHARMACOLOGY).
Cefixime

Cefixime

2.1 Adults

The recommended dose of cefixime is 400 mg daily. This may be given as a 400 mg tablet or capsule daily or the 400 mg tablet may be split and given as one half tablet every 12 hours. For the treatment of uncomplicated cervical/urethral gonococcal infections, a single oral dose of 400 mg is recommended. The capsule and tablet may be administered without regard to food.In the treatment of infections due to Streptococcus pyogenes, a therapeutic dosage of cefixime should be administered for at least 10 days.

2.2 Pediatric Patients (6 months or older)

The recommended dose is 8 mg/kg/day of the suspension. This may be administered as a single daily dose or may be given in two divided doses, as 4 mg/kg every 12 hours.

Note: A suggested dose has been determined for each pediatric weight range. Refer to Table 1. Ensure all orders that specify a dose in milliliters include a concentration, because cefixime for oral suspension is available in three different concentrations (100 mg/5 mL, 200 mg/5 mL, and 500 mg/5 mL).

Table 1. Suggested doses for pediatric patients * The preferred concentrations of oral suspension to use are 100 mg/5 mL or 200 mg/5 mL for pediatric patients in these weight ranges. PEDIATRIC DOSAGE CHART Doses are suggested for each weight range and rounded for ease of administration Cefixime for Oral Suspension Cefixime Chewable Tablet 100 mg/5 mL 200 mg/5 mL 500 mg/5 mL Patient Weight (kg) Dose/Day (mg) Dose/Day (mL) Dose/Day (mL) Dose/Day (mL) Dose 5 to 7.5* 50 2.5 -- -- -- 7.6 to 10* 80 4 2 -- -- 10.1 to 12.5 100 5 2.5 1 1 tablet of 100 mg 12.6 to 20.5 150 7.5 4 1.5 1 tablet of 150 mg 20.6 to 28 200 10 5 2 1 tablet of 200 mg 28.1 to 33 250 12.5 6 2.5 1 tablet of 100 mg and 1 tablet of 150 mg 33.1 to 40 300 15 7.5 3 2 tablets of 150 mg 40.1 to 45 350 17.5 9 3.5 1 tablet of 150 mg and 1 tablet of 200 mg 45.1 or greater 400 20 10 4 2 tablets of 200 mg
Children weighing more than 45 kg or older than 12 years should be treated with the recommended adult dose. Cefixime chewable tablets must be chewed or crushed before swallowing.

Otitis media should be treated with the chewable tablets or suspension. Clinical trials of otitis media were conducted with the chewable tablets or suspension, and the chewable tablets or suspension results in higher peak blood levels than the tablet when administered at the same dose.

Therefore, the tablet or capsule should not be substituted for the chewable tablets or suspension in the treatment of otitis media. [See CLINICAL PHARMACOLOGY (12.3).]

In the treatment of infections due to Streptococcus pyogenes, a therapeutic dosage of cefixime should be administered for at least 10 days.

2.3 Renal Impairment

Cefixime for oral suspension may be administered in the presence of impaired renal function. Normal dose and schedule may be employed in patients with creatinine clearances of 60 mL/min or greater. Refer to Table 2 for dose adjustments for adults with renal impairment. Neither hemodialysis nor peritoneal dialysis removes significant amounts of drug from the body.
Table 2. Doses for Adults with Renal Impairment * The preferred concentrations of oral suspension to use are 200 mg/5 mL or 500 mg/5 mL for patients with this renal dysfunction Renal Dysfunction Cefixime for Oral Suspension Tablet Chewable Tablet Creatinine Clearance (mL/min) 100 mg/5 mL 200 mg/5 mL 500 mg/5 mL 400 mg 200 mg Dose/Day (mL) Dose/Day (mL) Dose/Day (mL) Dose/Day Dose/Day 60 or greater Normal dose Normal dose Normal dose Normal dose Normal dose 21 to 59 * OR renal hemodialysis* 13 6.5 2.6 Not Appropriate Not Appropriate 20 or less OR continuous peritoneal dialysis 8.6 4.4 1.8 0.5 tablet 1 tablet
2.4 Reconstitution Directions for Oral Suspension
Strength Bottle Size Reconstitution Directions 100 mg/5 mL 100 mL To reconstitute, suspend with 70 mL water. Method: Tap the bottle several times to loosen powder contents prior to reconstitution. Add approximately half the total amount of water for reconstitution and shake well. Add the remainder of water and shake well. 200 mg/5 mL 75 mL To reconstitute, suspend with 52.5 mL water. Method: Tap the bottle several times to loosen powder contents prior to reconstitution. Add approximately half the total amount of water for reconstitution and shake well. Add the remainder of water and shake well. 100 mg/5 mL and 200 mg/5 mL 50 mL To reconstitute, suspend with 35 mL water. Method: Tap the bottle several times to loosen powder contents prior to reconstitution. Add approximately half the total amount of water for reconstitution and shake well. Add the remainder of water and shake well.
After reconstitution, the suspension may be kept for 14 days either at room temperature, or under refrigeration, without significant loss of potency. Keep tightly closed. Shake well before using. Discard unused portion after 14 days.
Naropin

Naropin

Table 1. Recommended Daily Dosage by Indication Initial Dose Titration(Increments) Target Dose Effective DoseRange Schizophrenia: adults (2.1) 2 mg 1 to 2 mg 4 to 8 mg 4 to 16 mg Schizophrenia: adolescents (2.2) 0.5 mg 0.5 to 1 mg 3 mg 1 to 6 mg Bipolar mania: adults (2.2) 2 to 3 mg 1 mg 1 to 6 mg 1 to 6 mg Bipolar mania: children and adolescents (2.2) 0.5 mg 0.5 to 1 mg 1 to 2.5 mg 1 to 6 mg Irritability in autistic disorder (2.3) 0.25 mg Can increase to 0.5 mg by Day 4: (body weight less than 20 kg) 0.5 mg Can increase to 1 mg by Day 4: (body weight greater than or equal to 20 kg) After Day 4, at intervals of > 2 weeks: 0.25 mg (body weight less than 20 kg) 0.5 mg (body weight greater than or equal to 20 kg) 0.5 mg: (body weight less than 20 kg) 1 mg: (body weightgreater than or equal to 20 kg) 0.5 to 3 mg
Severe Renal and Hepatic Impairment in Adults: use a lower starting dose of 0.5 mg twice daily. May increase to dosages above 1.5 mg twice daily at intervals of one week or longer

2.1 Schizophrenia

Adults Usual Initial Dose Risperidone oral solution can be administered once or twice daily. Initial dosing is 2 mg per day. May increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg per day, as tolerated, to a recommended dose of 4 to 8 mg per day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 mg to 16 mg per day. However, doses above 6 mg per day for twice daily dosing were not demonstrated to be more efficacious than lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are generally not recommended. In a single study supporting once-daily dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg per day has not been evaluated in clinical trials [see Clinical Studies (14.1)].Adolescents The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to a recommended dose of 3 mg per day. Although efficacy has been demonstrated in studies of adolescent patients with schizophrenia at doses between 1 mg to 6 mg per day, no additional benefit was observed above 3 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.Maintenance Therapy While it is unknown how long a patient with schizophrenia should remain on risperidone oral solution, the effectiveness of risperidone oral solution 2 mg per day to 8 mg per day at delaying relapse was demonstrated in a controlled trial in adult patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years [see Clinical Studies (14.1)]. Both adult and adolescent patients who respond acutely should generally be maintained on their effective dose beyond the acute episode. Patients should be periodically reassessed to determine the need for maintenance treatment.Reinitiation of Treatment in Patients Previously Discontinued Although there are no data to specifically address reinitiation of treatment, it is recommended that after an interval off risperidone oral solution, the initial titration schedule should be followed.Switching From Other Antipsychotics There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to risperidone oral solution, or treating patients with concomitant antipsychotics.

2.2 Bipolar Mania

Usual DoseAdultsThe initial dose range is 2 mg to 3 mg per day. The dose may be adjusted at intervals of 24 hours or greater, in increments of 1 mg per day. The effective dose range is 1 mg to 6 mg per day, as studied in the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was demonstrated in a flexible dosage range of 1 mg to 6 mg per day [see Clinical Studies (14.2, 14.3)]. Risperidone oral solution doses higher than 6 mg per day were not studied. Pediatrics The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to the recommended target dose of 1 mg to 2.5 mg per day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 mg and 6 mg per day, no additional benefit was observed above 2.5 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied. Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily. Maintenance TherapyThere is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of an acute manic episode with risperidone oral solution. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of risperidone oral solution in such longer-term treatment (i.e., beyond 3 weeks). The physician who elects to use risperidone oral solution for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3 Irritability Associated with Autistic Disorder - Pediatrics (Children and Adolescents)

The dosage of risperidone oral solution should be individualized according to the response and tolerability of the patient. The total daily dose of risperidone oral solution can be administered once daily, or half the total daily dose can be administered twice daily.For patients with body weight less than 20 kg, initiate dosing at 0.25 mg per day. For patients with body weight greater than or equal to 20 kg, initiate dosing at 0.5 mg per day. After a minimum of four days, the dose may be increased to the recommended dose of 0.5 mg per day for patients less than 20 kg and 1 mg per day for patients greater than or equal to 20 kg. Maintain this dose for a minimum of 14 days. In patients not achieving sufficient clinical response, the dose may be increased at intervals of 2 weeks or greater, in increments of 0.25 mg per day for patients less than 20 kg, or increments of 0.5 mg per day for patients greater than or equal to 20 kg. The effective dose range is 0.5 mg to 3 mg per day. No dosing data are available for children who weigh less than 15 kg.Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of efficacy and safety. The physician who elects to use risperidone oral solution for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime or administering half the daily dose twice daily, or a reduction of the dose.

2.4 Dosing in Patients with Severe Renal or Hepatic Impairment

For patients with severe renal impairment (CLcr < 30 mL/min) or hepatic impairment (10 to 15 points on Child Pugh System), the initial starting dose is 0.5 mg twice daily. The dose may be increased in increments of 0.5 mg or less, administered twice daily. For doses above 1.5 mg twice daily, increase in intervals of one week or greater [see Use in Specific Populations (8.6 and 8.7)].

2.5 Dose Adjustments for Specific Drug Interactions

When risperidone oral solution is co-administered with enzyme inducers (e.g., carbamazepine), the dose of risperidone oral solution should be increased up to double the patient's usual dose. It may be necessary to decrease the risperidone oral solution dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1)]. Similar effect may be expected with co-administration of risperidone oral solution with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).When fluoxetine or paroxetine is co-administered with risperidone oral solution, the dose of risperidone oral solution should be reduced. The risperidone oral solution dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, risperidone oral solution should be titrated slowly. It may be necessary to increase the risperidone oral solution dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1)].

2.6 Administration of Risperidone Oral Solution

Risperidone

oral solution can be administered directly from the

dispensing syringe, or can be mixed with a beverage prior to administration. Risperidone

oral solution is compatible in the following beverages: water, coffee, orange juice, and low-fat milk; it is NOT compatible with either cola or tea.
Cilostazol

Cilostazol

2.1 Dosage in Narcolepsy and Obstructive Sleep Apnea (OSA)

The recommended dosage of modafinil tablets for patients with narcolepsy or OSA is 200 mg taken orally once a day as a single dose in the morning.Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg/day dose [see Clinical Pharmacology (12.3) and Clinical Studies (14.1, 14.2)].

2.2 Dosage in Shift Work Disorder (SWD)

The recommended dosage of modafinil tablets for patients with SWD is 200 mg taken orally once a day as a single dose approximately 1 hour prior to the start of their work shift.

2.3 Dosage Modifications in Patients with Severe Hepatic Impairment

In patients with severe hepatic impairment, the dosage of modafinil tablets should be reduced to one-half of that recommended for patients with normal hepatic function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.4 Use in Geriatric Patients

Consideration should be given to the use of lower doses and close monitoring in geriatric patients [see Use in Specific Populations (8.5)].
Amoxicillin And Clavula...

Amoxicillin And Clavulanate Potassium

Amoxicillin and clavulanate potassium for oral suspension does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of amoxicillin and clavulanate potassium. Amoxicillin and clavulanate potassium for oral suspension contains 42.9 mg of clavulanic acid per 5 mL, whereas the 200 mg/5 mL suspension of amoxicillin and clavulanate potassium contains 28.5 mg of clavulanic acid per 5 mL and the 400 mg/5 mL suspension contains 57 mg of clavulanic acid per 5 mL. Therefore, the 200 mg/28.5 mg/5 mL and 400 mg/57 mg/5 mL suspensions of amoxicillin and clavulanate potassium should not be substituted for amoxicillin and clavulanate potassium for oral suspension as they are not interchangeable.

Dosage: Pediatric patients 3 months and older: Based on the amoxicillin component (600 mg/5 mL), the recommended dose of amoxicillin and clavulanate potassium for oral suspension is 90 mg/kg/day divided every 12 hours, administered for 10 days (see chart below). This dose provides 6.4 mg/kg/day of the clavulanic acid component.
Body Weight (kg) Volume of Amoxicillin and Clavulanate Potassium Powder for Oral Suspension providing 90 mg/kg/day 8 3 mL twice daily 12 4.5 mL twice daily 16 6 mL twice daily 20 7.5 mL twice daily 24 9 mL twice daily 28 10.5 mL twice daily 32 12 mL twice daily 36 13.5 mL twice daily
Pediatric patients weighing 40 kg and more: Experience with amoxicillin and clavulanate potassium for oral suspension in this group is not available.

Adults: Experience with amoxicillin and clavulanate potassium for oral suspension in adults is not available and adults who have difficulty swallowing should not be given amoxicillin and clavulanate potassium for oral suspension in place of the 500 mg or 875 mg tablet of amoxicillin and clavulanate potassium.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals [see WARNINGS and PRECAUTIONS (5)].

Directions for Mixing Oral Suspension: Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see table below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Amoxicillin and Clavulanate Potassium for Oral Suspension Bottle Size Amount of Water Required for Reconstitution 75 mL 71 mL 125 mL 112 mL 200 mL 176 mL
Each teaspoonful (5 mL) will contain 600 mg amoxicillin as the trihydrate and 42.9 mg of clavulanic acid as the potassium salt.

NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING.

Information for the Pharmacist: For patients who wish to alter the taste of amoxicillin and clavulanate potassium for oral suspension, immediately after reconstitution 1 drop of FLAVORx™ (apple, banana cream, bubble gum, cherry, or watermelon flavor) may be added for every 5 mL of amoxicillin and clavulanate potassium for oral suspension. The resulting suspension is stable for 10 days under refrigeration. Stability of amoxicillin and clavulanate potassium for oral suspension when mixed with other flavors distributed by FLAVORx has not been evaluated for flavors other than the five flavors listed above.

Administration: To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium for oral suspension should be taken at the start of a meal. Absorption of clavulanate potassium may be enhanced when amoxicillin and clavulanate potassium for oral suspension is administered at the start of a meal.
Bisoprolol Fumarate

Bisoprolol Fumarate

The dose of bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily. In some patients, 2.5 mg may be an appropriate starting dose (see Bronchospastic Disease in WARNINGS). If the antihypertensive effect of 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. Patients with Renal or Hepatic Impairment In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min), the initial daily dose should be 2.5 mg and caution should be used in dose-titration. Since limited data suggest that bisoprolol fumarate is not dialyzable, drug replacement is not necessary in patients undergoing dialysis. Geriatric Patients It is not necessary to adjust the dose in the elderly, unless there is also significant renal or hepatic dysfunction (see above and Geriatric Use in PRECAUTIONS). Pediatric Patients There is no pediatric experience with bisoprolol fumarate.
Didanosine

Didanosine

Didanosine delayed-release capsules should be administered on an empty stomach. Didanosine delayed-release capsules should be swallowed intact.
2.1 Recommended Dosage (Adult and Pediatric Patients)
The recommended total daily dose is based on body weight and is administered as one capsule given on a once-daily schedule as outlined in Table 1. The recommended total daily dose to be administered once daily to pediatric patients weighing at least 20 kg who can swallow capsules is based on body weight (kg), consistent with the recommended adult dosing guidelines (see Table 1). Please consult the complete prescribing information for didanosine pediatric powder for oral solution for dosage and administration of didanosine to pediatric patients weighing less than 20 kg or who can not swallow capsules. Table 1: Recommended Dosage (Adult and Pediatric Patients) Body Weight Dose 20 kg to less than 25 kg 200 mg once daily 25 kg to less than 60 kg 250 mg once daily at least 60 kg 400 mg once daily
2.2 Renal Impairment
Dosing recommendations for didanosine delayed-release capsules and didanosine pediatric powder for oral solution are different for patients with renal impairment. Please consult the complete prescribing information on administration of didanosine pediatric powder for oral solution to patients with renal impairment. Adult Patients In adult patients with impaired renal function, the dose of didanosine delayed-release capsules should be adjusted to compensate for the slower rate of elimination. The recommended doses and dosing intervals of didanosine delayed-release capsules in adult patients with renal insufficiency are presented in Table 2. Table 2: Recommended Dosage in Patients with Renal Impairment by Body Weighta CreatinineClearance (mL/min) Dosage (mg) at least 60 kg less than 60 kg a Based on studies using a buffered formulation of didanosine.b Not suitable for use in patients less than 60 kg with CLcr less than 10 mL/min. An alternate formulation of didanosine should be used. at least 6030-5910-29less than 10 400 once daily200 once daily125 once daily125 once daily 250 once daily125 once daily125 once dailyb Pediatric Patients Urinary excretion is also a major route of elimination of didanosine in pediatric patients, therefore the clearance of didanosine may be altered in pediatric patients with renal impairment. Although there are insufficient data to recommend a specific dose adjustment of didanosine delayed-release capsules in this patient population, a reduction in the dose should be considered (see Table 2). Patients Requiring Continuous Ambulatory Peritoneal Dialysis (CAPD) or Hemodialysis For patients requiring CAPD or hemodialysis, follow dosing recommendations for patients with creatinine clearance of less than 10 mL/min, shown in Table 2. It is not necessary to administer a supplemental dose of didanosine following hemodialysis.
2.3 Dose Adjustment
Concomitant Therapy with Tenofovir Disoproxil Fumarate In patients who are also taking tenofovir disoproxil fumarate, a dose reduction of didanosine delayed-release capsules to 250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min) or 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min) once daily taken together with tenofovir disoproxil fumarate and a light meal (400 kcalories or less, 20% fat or less) or in the fasted state is recommended. The appropriate dose of didanosine delayed-release capsules coadministered with tenofovir disoproxil fumarate in patients with creatinine clearance of less than 60 mL/min has not been established [see Drug Interactions (7) and Clinical Pharmacology (12.3)]. Hepatic Impairment No dose adjustment is required in patients with hepatic impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].
Hydrochlorothiazide

Hydrochlorothiazide

Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.
Adults

For Edema
The usual adult dosage is 25 mg to 100 mg daily as a single or divided dose. Many patients with edema respond to intermittent therapy, i.e., administration on alternate days or on 3 to 5 days each week. With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.
For Control of Hypertension
The usual initial dose in adults is 25 mg daily given as a single dose. The dose may be increased to 50 mg daily, given as a single or two divided doses. Doses above 50 mg are often associated with marked reductions in serum potassium (see also PRECAUTIONS). Patients usually do not require doses in excess of 50 mg of hydrochlorothiazide daily when used concomitantly with other antihypertensive agents.
Infants and Children

For Diuresis and for Control of Hypertension
The usual pediatric dosage is 0.5 mg to 1 mg per pound (1 to 2 mg/kg) per day in single or two divided doses, not to exceed 37.5 mg per day in infants up to 2 years of age or 100 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 1.5 mg per pound (3 mg/kg) per day in two divided doses may be required. (See PRECAUTIONS, Pediatric Use.)
Lamivudine

Lamivudine

2.1 Adults and Adolescents >16 years of age
The recommended oral dose of lamivudine tablets in HIV-1-infected adults and adolescents >16 years of age is 300 mg daily, administered as either 150 mg twice daily or 300 mg once daily, in combination with other antiretroviral agents. If lamivudine is administered to a patient infected with HIV-1 and HBV, the dosage indicated for HIV-1 therapy should be used as part of an appropriate combination regimen [see Warnings and Precautions (5.2)].
2.2 Pediatric Patients
Lamivudine tablets are available as scored tablets for HIV-1-infected pediatric patients who weigh ≥14 kg for whom a solid dosage form is appropriate. Before prescribing lamivudine tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow lamivudine tablets, the oral solution formulation should be prescribed. The recommended oral dosage of lamivudine tablets for HIV-1-infected pediatric patients is presented in Table 1. Table 1. Dosing Recommendations for Lamivudine Tablets in Pediatric Patients Weight (kg) Dosage Regimen Using Scored150 mg Tablet TotalDaily Dose AM Dose PM Dose 14 to 21 ½ tablet (75 mg) ½ tablet (75 mg) 150 mg >21 to <30 ½ tablet (75 mg) 1 tablet (150 mg) 225 mg ≥30 1 tablet (150 mg) 1 tablet (150 mg) 300 mg
2.3 Patients With Renal Impairment
Dosing of lamivudine tablets is adjusted in accordance with renal function. Dosage adjustments are listed in Table 2 [see Clinical Pharmacology (12.3)]. Table 2. Adjustment of Dosage of Lamivudine Tablets in Adults and Adolescents (≥30 kg) in Accordance With Creatinine Clearance Creatinine Clearance (mL/min) Recommended Dosage of Lamivudine Tablets ≥50 150 mg twice daily or 300 mg once daily 30-49 150 mg once daily 15-29 150 mg first dose, then 100 mg once daily 5-14 150 mg first dose, then 50 mg once daily <5 50 mg first dose, then 25 mg once daily No additional dosing of lamivudine tablets is required after routine (4-hour) hemodialysis or peritoneal dialysis. Although there are insufficient data to recommend a specific dose adjustment of lamivudine tablets in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval should be considered.
Lamivudine And Zidovudi...

Lamivudine And Zidovudine

2.1 Adults and Adolescents Weighing ≥30 kg
The recommended oral dose of lamivudine and zidovudine tablets in HIV-1-infected adults and adolescents weighing greater than or equal to 30 kg is 1 tablet (containing 150 mg of lamivudine and 300 mg of zidovudine) twice daily.
2.2 Pediatric Patients
The recommended oral dosage of scored lamivudine and zidovudine tablets for pediatric patients who weigh greater than or equal to 30 kg and for whom a solid oral dosage form is appropriate is 1 tablet administered twice daily. Before prescribing lamivudine and zidovudine tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a lamivudine and zidovudine tablet, the liquid oral formulations should be prescribed: EPIVIR ® (lamivudine) oral solution and RETROVIR ® (zidovudine) syrup.
2.3 Patients Requiring Dosage Adjustment
Because lamivudine and zidovudine is a fixed-dose combination tablet, it should not be prescribed for pediatric patients weighing less than 30 kg or patients requiring dosage adjustment, such as those with reduced renal function (creatinine clearance less than 50 mL/min), patients with hepatic impairment, or patients experiencing dose-limiting adverse reactions. Liquid and solid oral formulations of the individual components of lamivudine and zidovudine are available for these populations.
Valacyclovir Hydrochlor...

Valacyclovir Hydrochloride

Valacyclovir tablets may be given without regard to meals.
Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) may be prepared extemporaneously from 500 mg valacyclovir tablets for use in pediatric patients for whom a solid dosage form is not appropriate [see Dosage and Administration (2.3)].

2.1 Adult Dosing Recommendations
Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir tablets for treatment of cold sores is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning). Genital Herpes: Initial Episode: The recommended dosage of valacyclovir tablets for treatment of initial genital herpes is 1 gram twice daily for 10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms. Recurrent Episodes: The recommended dosage of valacyclovir tablets for treatment of recurrent genital herpes is 500 mg twice daily for 3 days. Initiate treatment at the first sign or symptom of an episode. Suppressive Therapy: The recommended dosage of valacyclovir tablets for chronic suppressive therapy of recurrent genital herpes is 1 gram once daily in patients with normal immune function. In patients with a history of 9 or fewer recurrences per year, an alternative dose is 500 mg once daily. In HIV-infected patients with a CD4+ cell count ≥100 cells/mm 3, the recommended dosage of valacyclovir tablets for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily. Reduction of Transmission: The recommended dosage of valacyclovir tablets for reduction of transmission of genital herpes in patients with a history of 9 or fewer recurrences per year is 500 mg once daily for the source partner. Herpes Zoster: The recommended dosage of valacyclovir tablets for treatment of herpes zoster is 1 gram 3 times daily for 7 days. Therapy should be initiated at the earliest sign or symptom of herpes zoster and is most effective when started within 48 hours of the onset of rash.
2.2 Pediatric Dosing Recommendations
Cold Sores (Herpes Labialis): The recommended dosage of valacyclovir tablets for the treatment of cold sores in pediatric patients ≥12 years of age is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).
Chickenpox: The recommended dosage of valacyclovir tablets for treatment of chickenpox in immunocompetent pediatric patients 2 to <18 years of age is 20 mg/kg administered 3 times daily for 5 days. The total dose should not exceed 1 gram 3 times daily. Therapy should be initiated at the earliest sign or symptom [see Use in Specific Populations (8.4), Clinical Pharmacology (12.3), Clinical Studies (14.4)].

2.3 Extemporaneous Preparation of Oral Suspension
Ingredients and Preparation per USP-NF: Valacyclovir tablets 500 mg, cherry flavor, and Suspension Structured Vehicle USP-NF (SSV). Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) should be prepared in lots of 100 mL. Prepare Suspension at Time of Dispensing as Follows: Prepare SSV according to the USP-NF. Using a pestle and mortar, grind the required number of valacyclovir 500 mg tablets until a fine powder is produced (5 valacyclovir tablets for 25 mg/mL suspension; 10 valacyclovir tablets for 50 mg/mL suspension). Gradually add approximately 5 mL aliquots of SSV to the mortar and triturate the powder until a paste has been produced. Ensure that the powder has been adequately wetted. Continue to add approximately 5 mL aliquots of SSV to the mortar, mixing thoroughly between additions, until a concentrated suspension is produced, to a minimum total quantity of 20 mL SSV and a maximum total quantity of 40 mL SSV for both the 25 mg/mL and 50 mg/mL suspensions. Transfer the mixture to a suitable 100 mL measuring flask. Transfer the cherry flavor* to the mortar and dissolve in approximately 5 mL of SSV. Once dissolved, add to the measuring flask. Rinse the mortar at least 3 times with approximately 5 mL aliquots of SSV, transferring the rinsing to the measuring flask between additions. Make the suspension to volume (100 mL) with SSV and shake thoroughly to mix. Transfer the suspension to an amber glass medicine bottle with a child-resistant closure. The prepared suspension should be labeled with the following information “Shake well before using. Store suspension between 2° to 8°C (36° to 46°F) in a refrigerator. Discard after 28 days.” *The amount of cherry flavor added is as instructed by the suppliers of the cherry flavor.
2.4 Patients With Renal Impairment
Dosage recommendations for adult patients with reduced renal function are provided in Table 1 [see Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)]. Data are not available for the use of valacyclovir tablets in pediatric patients with a creatinine clearance <50 mL/min/1.73 m 2. Table 1. Valacyclovir Tablets Dosage Recommendations for Adults With Renal Impairment Indications Normal Dosage Regimen(Creatinine Clearance ≥50) Creatinine Clearance (mL/min) 30-49 10-29 <10 Cold sores (Herpes labialis) Do not exceed 1 day of treatment. Two 2 gramdoses taken12 hours apart Two 1 gramdoses taken12 hours apart Two 500 mgdoses taken12 hours apart 500 mg single dose Genital herpes: Initial episode 1 gram every 12 hours no reduction 1 gram every24 hours 500 mg every 24 hours Genital herpes: Recurrent episode 500 mg every 12 hours no reduction 500 mg every24 hours 500 mg every 24 hours Genital herpes: Suppressive therapy Immunocompetent patients Alternate dose for immunocompetent patient with ≤9 recurrences/year HIV-infected patients 1 gram every 24 hours 500 mg every 24 hours 500 mg every 12 hours no reduction no reduction no reduction 500 mg every24 hours 500 mg every48 hours 500 mg every24 hours 500 mg every24 hours 500 mg every48 hours 500 mg every24 hours Herpes zoster 1 gram every 8 hours 1 gram every12 hours 1 gram every24 hours 500 mg every24 hours Hemodialysis: Patients requiring hemodialysis should receive the recommended dose of valacyclovir tablets after hemodialysis. During hemodialysis, the half-life of acyclovir after administration of valacyclovir tablets is approximately 4 hours. About one third of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session. Peritoneal Dialysis: There is no information specific to administration of valacyclovir tablets in patients receiving peritoneal dialysis. The effect of chronic ambulatory peritoneal dialysis (CAPD) and continuous arteriovenous hemofiltration/dialysis (CAVHD) on acyclovir pharmacokinetics has been studied. The removal of acyclovir after CAPD and CAVHD is less pronounced than with hemodialysis, and the pharmacokinetic parameters closely resemble those observed in patients with end-stage renal disease (ESRD) not receiving hemodialysis. Therefore, supplemental doses of valacyclovir tablets should not be required following CAPD or CAVHD.
Metformin Hydrochloride...

Metformin Hydrochloride

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with metformin hydrochloride extended-release tablets or any other pharmacologic agent. Dosage of metformin hydrochloride extended-release tablets must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum recommended daily dose of metformin hydrochloride extended-release tablets in adults is 2000 mg. Metformin hydrochloride extended-release tablets should generally be given once daily with the evening meal. Metformin hydrochloride extended-release tablets should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to metformin hydrochloride extended-release tablets and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of metformin hydrochloride extended-release tablets, either when used as monotherapy or in combination with sulfonylurea or insulin. Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness. Short-term administration of metformin hydrochloride extended-release tablets may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone. Metformin hydrochloride extended-release tablets must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of metformin hydrochloride extended-release tablets will be eliminated in the feces as a soft, hydrated mass. (See Patient Information printed below.)
Recommended Dosing Schedule
Adults In general, clinically significant responses are not seen at doses below 1500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms. The usual starting dose of metformin hydrochloride extended-release tablets is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on metformin hydrochloride extended-release tablets 2000 mg once daily, a trial of metformin hydrochloride extended-release tablets 1000 mg twice daily should be considered. (See CLINICAL PHARMACOLOGY: Clinical Studies.) In a randomized trial, patients currently treated with metformin hydrochloride tablets were switched to metformin hydrochloride extended-release tablets. Results of this trial suggest that patients receiving metformin hydrochloride tablets treatment may be safely switched to metformin hydrochloride extended-release tablets once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from metformin hydrochloride tablets to metformin hydrochloride extended-release tablets, glycemic control should be closely monitored and dosage adjustments made accordingly (see CLINICAL PHARMACOLOGY: Clinical Studies). Pediatrics Safety and effectiveness of metformin hydrochloride extended-release tablets in pediatric patients have not been established. Transfer From Other Antidiabetic Therapy When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to metformin hydrochloride extended-release tablets, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first two weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.
Concomitant Metformin Hydrochloride Extended-Release Tablets and Oral Sulfonylurea Therapy in Adult Patients
If patients have not responded to four weeks of the maximum dose of metformin hydrochloride extended-release tablet monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin hydrochloride extended-release tablets at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for metformin plus glyburide (glibenclamide). With concomitant metformin hydrochloride extended-release tablet and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant metformin hydrochloride extended-release tablet and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken. (See Package Insert of the respective sulfonylurea.) If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of metformin hydrochloride extended-release tablets and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without metformin hydrochloride extended-release tablets. Concomitant Metformin Hydrochloride Extended-Release Tablets and Insulin Therapy in Adult Patients The current insulin dose should be continued upon initiation of metformin hydrochloride extended-release tablets therapy. Metformin hydrochloride extended-release tablets therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of metformin hydrochloride extended release-tablets should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2000 mg for metformin hydrochloride extended-release tablets. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and metformin hydrochloride extended-release tablets. Further adjustment should be individualized based on glucose-lowering response. Specific Patient Populations Metformin hydrochloride extended-release tablets are not recommended for use in pregnancy. Metformin hydrochloride extended-release tablets are not recommended in pediatric patients (below the age of 17 years). The initial and maintenance dosing of metformin hydrochloride extended-release tablets should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of metformin hydrochloride extended-release tablets. Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly. (See WARNINGS.)
Dandruff

Dandruff

2.1 Important Administration Instructions
Cefuroxime axetil tablets and cefuroxime axetil for oral suspension are not bioequivalent and are therefore not substitutable on a milligram-per-milligram basis [see Clinical Pharmacology (12.3)]. Administer cefuroxime axetil tablets as described in the appropriate dosage guidelines [see Dosage and Administration (2.2)]. Administer cefuroxime axetil tablets with or without food. Pediatric patients (aged 13 years and older) who cannot swallow the cefuroxime axetil tablets whole should receive cefuroxime axetil for oral suspension because the tablet has a strong, persistent bitter taste when crushed [see Dosage and Administration (2.2)].
2.2 Dosage for Cefuroxime Axetil Tablets

Administer cefuroxime axetil tablets as described in the dosage guidelines table below with or without food.
Table 1. Adult Patients and Pediatric Patients Dosage Guidelines for Cefuroxime Axetil Tablets a The safety and effectiveness of cefuroxime axetil tablets administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established. b When crushed, the tablet has a strong, persistent bitter taste. Therefore, patients who cannot swallow the tablet whole should receive the oral suspension. Infection Dosage Duration (Days) Adults and Adolescents (13 years and older) Pharyngitis/tonsillitis (mild to moderate) 250 mg every 12 hours 10 Acute bacterial maxillary sinusitis (mild to moderate) 250 mg every 12 hours 10 Acute bacterial exacerbations of chronic bronchitis (mild to moderate) 250 mg or 500 mg every12 hours 10a Secondary bacterial infections of acute bronchitis 250 mg or 500 mg every12 hours 5 to 10 Uncomplicated skin and skin-structure infections 250 mg or 500 mg every12 hours 10 Uncomplicated urinary tract infections 250 mg every 12 hours 7 to 10 Uncomplicated gonorrhea 1,000 mg single dose Early Lyme disease 500 mg every 12 hours 20 Pediatric Patients younger than 13 years (who can swallow tablets whole)b Acute bacterial otitis media 250 mg every 12 hours 10 Acute bacterial maxillary sinusitis 250 mg every 12 hours 10
2.5 Dosage in Patients with Impaired Renal Function

A dosage interval adjustment is required for patients whose creatinine clearance is <30 mL/min, as listed in Table 4 below, because cefuroxime is eliminated primarily by the kidney [see Clinical Pharmacology (12.3)].
Table 4. Dosing in Adults with Renal Impairment Creatinine Clearance (mL/min) Recommended Dosage ≥30 No dosage adjustment 10 to <30 Standard individual dose given every 24 hours <10 (without hemodialysis) Standard individual dose given every 48 hours Hemodialysis A single additional standard dose should be given at the end of each dialysis
Granisetron Hydrochlori...

Granisetron Hydrochloride

Hypertension MonotherapyThe recommended initial dosage of quinapril tablets in patients not on diuretics is 10 or 20 mg once daily. Dosage should be adjusted according to blood pressure response measured at peak (2 to 6 hours after dosing) and trough (predosing). Generally, dosage adjustments should be made at intervals of at least 2 weeks. Most patients have required dosages of 20, 40, or 80 mg/day, given as a single dose or in two equally divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients an increase in dosage or twice daily administration may be warranted. In general, doses of 40 to 80 mg and divided doses give a somewhat greater effect at the end of the dosing interval.Concomitant DiureticsIf blood pressure is not adequately controlled with quinapril tablets monotherapy, a diuretic may be added. In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of quinapril tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with quinapril tablets (see WARNINGS). Then, if blood pressure is not controlled with quinapril tablets alone, diuretic therapy should be resumed.If the diuretic cannot be discontinued, an initial dose of 5 mg quinapril tablets should be used with careful medical supervision for several hours and until blood pressure has stabilized.The dosage should subsequently be titrated (as described above) to the optimal response (see WARNINGS and PRECAUTIONS, Drug Interactions).Renal ImpairmentKinetic data indicate that the apparent elimination half-life of quinaprilat increases as creatinine clearance decreases. Recommended starting doses, based on clinical and pharmacokinetic data from patients with renal impairment, are as follows:
Creatinine Clearance Maximum RecommendedInitial Dose >60 mL/min 10 mg 30 to 60 mL/min 5 mg 10 to 30 mL/min 2.5 mg <10 mL/min Insufficient data for dosage recommendation
Patients should subsequently have their dosage titrated (as described above) to the optimal response.Elderly (≥65 years)The recommended initial dosage of quinapril tablets in elderly patients is 10 mg given once daily followed by titration (as described above) to the optimal response. Heart Failure Quinapril tablets are indicated as adjunctive therapy when added to conventional therapy including diuretics and/or digitalis. The recommended starting dose is 5 mg twice daily. This dose may improve symptoms of heart failure, but increases in exercise duration have generally required higher doses. Therefore, if the initial dosage of quinapril tablets is well tolerated, patients should then be titrated at weekly intervals until an effective dose, usually 20 to 40 mg daily given in two equally divided doses, is reached or undesirable hypotension, orthostatis, or azotemia (see WARNINGS) prohibit reaching this dose.Following the initial dose of quinapril tablets, the patient should be observed under medical supervision for at least two hours for the presence of hypotension or orthostatis and, if present, until blood pressure stabilizes. The appearance of hypotension, orthostatis, or azotemia early in dose titration should not preclude further careful dose titration. Consideration should be given to reducing the dose of concomitant diuretics. DOSE ADJUSTMENTS IN PATIENTS WITH HEART FAILURE AND RENAL IMPAIRMENT OR HYPONATREMIA Pharmacokinetic data indicate that quinapril elimination is dependent on level of renal function. In patients with heart failure and renal impairment, the recommended initial dose of quinapril tablets is 5 mg in patients with a creatinine clearance above 30 mL/min and 2.5 mg in patients with a creatinine clearance of 10 to 30 mL/min. There is insufficient data for dosage recommendation in patients with a creatinine clearance less than 10 mL/min (see DOSAGE AND ADMINISTRATION, Heart Failure, WARNINGS, and PRECAUTIONS, Drug Interactions).If the initial dose is well tolerated, quinapril tablets may be administered the following day as a twice daily regimen. In the absence of excessive hypotension or significant deterioration of renal function, the dose may be increased at weekly intervals based on clinical and hemodynamic response.
Carvedilol

Carvedilol

Carvedilol tablets should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects.
2.2 Left Ventricular Dysfunction Following Myocardial Infarction
DOSAGE MUST BE INDIVIDUALIZED AND MONITORED DURING UP-TITRATION. Treatment with carvedilol tablets may be started as an inpatient or outpatient and should be started after the patient is hemodynamically stable and fluid retention has been minimized. It is recommended that carvedilol tablets be started at 6.25 mg twice daily and increased after 3 to 10 days, based on tolerability, to 12.5 mg twice daily, then again to the target dose of 25 mg twice daily. A lower starting dose may be used (3.125 mg twice daily) and/or the rate of up-titration may be slowed if clinically indicated (e.g., due to low blood pressure or heart rate, or fluid retention). Patients should be maintained on lower doses if higher doses are not tolerated. The recommended dosing regimen need not be altered in patients who received treatment with an IV or oral β-blocker during the acute phase of the myocardial infarction.
2.3 Hypertension
DOSAGE MUST BE INDIVIDUALIZED. The recommended starting dose of carvedilol tablets is 6.25 mg twice daily. If this dose is tolerated, using standing systolic pressure measured about 1 hour after dosing as a guide, the dose should be maintained for 7 to 14 days, and then increased to 12.5 mg twice daily if needed, based on trough blood pressure, again using standing systolic pressure one hour after dosing as a guide for tolerance. This dose should also be maintained for 7 to 14 days and can then be adjusted upward to 25 mg twice daily if tolerated and needed. The full antihypertensive effect of carvedilol tablets is seen within 7 to 14 days. Total daily dose should not exceed 50 mg. Concomitant administration with a diuretic can be expected to produce additive effects and exaggerate the orthostatic component of carvedilol action.
2.4 Hepatic Impairment
Carvedilol tablets should not be given to patients with severe hepatic impairment [see Contraindications (4)].
Hydrochlorothiazide

Hydrochlorothiazide

For Control of Hypertension: The adult initial dose of hydrochlorothiazide is one capsule given once daily whether given alone or in combination with other antihypertensives. Total daily doses greater than 50 mg are not recommended.
Benazepril Hydrochlorid...

Benazepril Hydrochloride And Hydrochlorothiazide

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with metformin or any other pharmacologic agent. Dosage of metformin must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum recommended daily dose of metformin hydrochloride tablets is 2550 mg in adults and 2000 mg in pediatric patients (10 to 16 years of age).Metformin hydrochloride tablets should be given in divided doses with meals and should be started at a low dose, with gradual dose escalation, to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to metformin and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of metformin, either when used as monotherapy or in combination with sulfonylurea or insulin. Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.Short-term administration of metformin may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

Recommended Dosing Schedule

Adults - In general, clinically significant responses are not seen at doses below 1500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms.The usual starting dose of metformin hydrochloride tablets is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, metformin hydrochloride tablets may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals. Pediatrics – The usual starting dose of metformin hydrochloride tablets is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Transfer From Other Antidiabetic Therapy

When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to metformin, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first two weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Concomitant Metformin and Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to four weeks of the maximum dose of metformin monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for metformin plus glyburide (glibenclamide).With concomitant metformin and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. In a clinical trial of patients with type 2 diabetes and prior failure on glyburide, patients started on metformin hydrochloride tablets 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg or 2500/20 mg of metformin hydrochloride tablets and glyburide, respectively, to reach the goal of glycemic control as measured by FPG, HbA1c and plasma glucose response (see CLINICAL PHARMACOLOGY: Clinical Studies). However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant metformin and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken. (See Package Insert of the respective sulfonylurea.)If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of metformin and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without metformin.

Concomitant Metformin and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of metformin therapy. Metformin therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of metformin should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2500 mg for metformin hydrochloride tablets. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and metformin. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

Metformin is not recommended for use in pregnancy. Metformin hydrochloride tablets are not recommended in patients below the age of 10 years.The initial and maintenance dosing of metformin should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of metformin.Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly. (See WARNINGS.)
Torsemide

Torsemide

General Torsemide tablets may be given at any time in relation to a meal, as convenient. Special dosage adjustment in the elderly is not necessary.Congestive Heart Failure The usual initial dose is 10 mg or 20 mg of once-daily oral torsemide. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200 mg have not been adequately studied.Chronic Renal Failure The usual initial dose of torsemide is 20 mg of once-daily oral torsemide. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 200 mg have not been adequately studied.Hepatic Cirrhosis The usual initial dose is 5 mg or 10 mg of once-daily oral torsemide, administered together with an aldosterone antagonist or a potassium-sparing diuretic. If the diuretic response is inadequate, the dose should be titrated upward by approximately doubling until the desired diuretic response is obtained. Single doses higher than 40 mg have not been adequately studied.Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.Hypertension The usual initial dose is 5 mg once daily. If the 5 mg dose does not provide adequate reduction in blood pressure within 4 to 6 weeks, the dose may be increased to 10 mg once daily. If the response to 10 mg is insufficient, an additional antihypertensive agent should be added to the treatment regimen.
Sulfamethoxazole And Tr...

Sulfamethoxazole And Trimethoprim

Sulfamethoxazole and trimethoprim tablets are contraindicated in pediatric patients less than 2 months of age.
Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children

Adults
The usual adult dosage in the treatment of urinary tract infections is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet or 2 sulfamethoxazole and trimethoprim tablets every 12 hours for 10 to 14 days. An identical daily dosage is used for 5 days in the treatment of shigellosis.
Children
The recommended dose for children with urinary tract infections or acute otitis media is 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. The following table is a guideline for the attainment of this dosage: Children 2 months of age or older: Weight Dose–every 12 hours lb kg Tablets 22446688 10203040 –11½2 or 1 DS tablet
For Patients with Impaired Renal Function
When renal function is impaired, a reduced dosage should be employed using the following table: Creatinine Clearance (mL/min) Recommended Dosage Regimen Above 3015–30Below 15 Usual standard regimen½ the usual regimenUse not recommended
Acute Exacerbations of Chronic Bronchitis in Adults
The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet or 2 sulfamethoxazole and trimethoprim tablets every 12 hours for 14 days. Pneumocystis Jiroveci Pneumonia Treatment Adults and Children The recommended dosage for treatment of patients with documented Pneumocystis jiroveci pneumonia is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days. 11 The following table is a guideline for the upper limit of this dosage: Weight Dose–every 6 hours lb kg Tablets 1835537088106141176 816243240486480 –11½2 or 1 DS tablet2½3 or 1½ DS tablets4 or 2 DS tablets5 or 2½ DS tablets For the lower limit dose (75 mg/kg sulfamethoxazole and 15 mg/kg trimethoprim per 24 hours) administer 75% of the dose in the above table. Prophylaxis Adults The recommended dosage for prophylaxis in adults is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet daily. 12 ChildrenFor children, the recommended dose is 750 mg/m 2/day sulfamethoxazole with 150 mg/m 2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week. The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim. 13 The following table is a guideline for the attainment of this dosage in children: Body Surface Area Dose–every 12 hours (m2) Tablets 0.260.531.06 –½1
Traveler's Diarrhea in Adults
For the treatment of traveler’s diarrhea, the usual adult dosage is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet or 2 sulfamethoxazole and trimethoprim tablets every 12 hours for 5 days.
Felodipine

Felodipine

The recommended starting dose is 5 mg once a day. Depending on the patient’s response, the dosage can be decreased to 2.5 mg or increased to 10 mg once a day. These adjustments should occur generally at intervals of not less than 2 weeks. The recommended dosage range is 2.5 to 10 mg once daily. In clinical trials, doses above 10 mg daily showed an increased blood pressure response but a large increase in the rate of peripheral edema and other vasodilatory adverse events (see ADVERSE REACTIONS). Modification of the recommended dosage is usually not required in patients with renal impairment. Felodipine extended-release tablets should regularly be taken either without food or with a light meal (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism). Felodipine extended-release tablets should be swallowed whole and not crushed or chewed. Geriatric Use Patients over 65 years of age are likely to develop higher plasma concentrations of felodipine (see CLINICAL PHARMACOLOGY). In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range (2.5 mg daily). Elderly patients should have their blood pressure closely monitored during any dosage adjustment. Patients with Impaired Liver Function Patients with impaired liver function may have elevated plasma concentrations of felodipine and may respond to lower doses of felodipine extended-release tablets; therefore, patients should have their blood pressure monitored closely during dosage adjustment of felodipine extended-release tablets (see CLINICAL PHARMACOLOGY).
Childrens Cetirizine Hy...

Childrens Cetirizine Hydrochloride Allergy

use only with enclosed dosing cup adults and children 6 years and over 1 teaspoonful (5 mL) or 2 teaspoonfuls (10 mL) once daily depending upon severity of symptoms; do not take more than 2 teaspoonfuls (10 mL) in 24 hours. adults 65 years and over 1 teaspoonful (5 mL) once daily; do not take more than 1 teaspoonful (5 mL) in 24 hours. children 2 to under 6 years of age ½ teaspoonful (2.5 mL) once daily. If needed, dose can be increased to a maximum of 1 teaspoonful (5 mL) once daily or ½ teaspoonful (2.5 mL) every 12 hours. Do not give more than 1 teaspoonful (5 mL) in 24 hours. children under 2 years of age ask a doctor consumers with liver or kidney disease ask a doctor
Childrens Cetirizine Hy...

Childrens Cetirizine Hydrochloride Hives Relief

use only with enclosed dosing cup adults and children 6 years and over 1 teaspoonful (5 mL) or 2 teaspoonfuls (10 mL) once daily depending upon severity of symptoms; do not take more than 2 teaspoonfuls (10 mL) in 24 hours. adults 65 years and over 1 teaspoonful (5 mL) once daily; do not take more than 1 teaspoonful (5 mL) in 24 hours. children under 6 years of age ask a doctor consumers with liver or kidney disease ask a doctor
Sertraline Hydrochlorid...

Sertraline Hydrochloride

Initial Treatment Dosage for Adults Major Depressive Disorder and Obsessive-Compulsive Disorder Sertraline hydrochloride tablets treatment should be administered at a dose of 50 mg once daily. Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder Sertraline hydrochloride tablets treatment should be initiated with a dose of 25 mg once daily. After one week, the dose should be increased to 50 mg once daily. While a relationship between dose and effect has not been established for major depressive disorder, OCD, panic disorder, PTSD or social anxiety disorder, patients were dosed in a range of 50 to 200 mg/day in the clinical trials demonstrating the effectiveness of sertraline hydrochloride tablets for the treatment of these indications. Consequently, a dose of 50 mg, administered once daily, is recommended as the initial therapeutic dose. Patients not responding to a 50 mg dose may benefit from dose increases up to a maximum of 200 mg/day. Given the 24 hour elimination half-life of sertraline hydrochloride, dose changes should not occur at intervals of less than 1 week. Premenstrual Dysphoric Disorder Sertraline hydrochloride tablets treatment should be initiated with a dose of 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment. While a relationship between dose and effect has not been established for PMDD, patients were dosed in the range of 50 to 150 mg/day with dose increases at the onset of each new menstrual cycle (see Clinical Trials under CLINICAL PHARMACOLOGY). Patients not responding to a 50 mg/day dose may benefit from dose increases (at 50 mg increments/menstrual cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100 mg/day dose has been established with luteal phase dosing, a 50 mg/day titration step for three days should be utilized at the beginning of each luteal phase dosing period. Sertraline hydrochloride tablets should be administered once daily, either in the morning or evening. Dosage for Pediatric Population (Children and Adolescents) Obsessive-Compulsive Disorder Sertraline hydrochloride tablets treatment should be initiated with a dose of 25 mg once daily in children (ages 6 to 12) and at a dose of 50 mg once daily in adolescents (ages 13 to 17). While a relationship between dose and effect has not been established for OCD, patients were dosed in a range of 25 to 200 mg/day in the clinical trials demonstrating the effectiveness of sertraline hydrochloride tablets for pediatric patients (6 to 17 years) with OCD. Patients not responding to an initial dose of 25 or 50 mg/day may benefit from dose increases up to a maximum of 200 mg/day. For children with OCD, their generally lower body weights compared to adults should be taken into consideration in advancing the dose, in order to avoid excess dosing. Given the 24 hour elimination half-life of sertraline hydrochloride, dose changes should not occur at intervals of less than 1 week. Sertraline hydrochloride tablets should be administered once daily, either in the morning or evening. Maintenance/Continuation/Extended Treatment Major Depressive Disorder It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy beyond response to the acute episode. Systematic evaluation of sertraline hydrochloride tablets have demonstrated that its antidepressant efficacy is maintained for periods of up to 44 weeks following 8 weeks of initial treatment at a dose of 50 to 200 mg/day (mean dose of 70 mg/day) (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride tablets needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment. Posttraumatic Stress Disorder It is generally agreed that PTSD requires several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline hydrochloride tablets has demonstrated that its efficacy in PTSD is maintained for periods of up to 28 weeks following 24 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride tablets needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment. Social Anxiety Disorder Social anxiety disorder is a chronic condition that may require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline hydrochloride tablets has demonstrated that its efficacy in social anxiety disorder is maintained for periods of up to 24 weeks following 20 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). Dosage adjustments should be made to maintain patients on the lowest effective dose and patients should be periodically reassessed to determine the need for long-term treatment. Obsessive-Compulsive Disorder and Panic Disorder It is generally agreed that OCD and Panic Disorder require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of continuing sertraline hydrochloride tablets for periods of up to 28 weeks in patients with OCD and Panic Disorder who have responded while taking sertraline hydrochloride tablets during initial treatment phases of 24 to 52 weeks of treatment at a dose range of 50 to 200 mg/day has demonstrated a benefit of such maintenance treatment (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride tablets needed for maintenance treatment is identical to the dose needed to achieve an initial response. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment. Premenstrual Dysphoric Disorder The effectiveness of sertraline hydrochloride tablets in long-term use, that is, for more than 3 menstrual cycles, has not been systematically evaluated in controlled trials. However, as women commonly report that symptoms worsen with age until relieved by the onset of menopause, it is reasonable to consider continuation of a responding patient. Dosage adjustments, which may include changes between dosage regimens (e.g., daily throughout the menstrual cycle versus during the luteal phase of the menstrual cycle), may be needed to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment. Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with sertraline hydrochloride tablets. Conversely, at least 14 days should be allowed after stopping sertraline hydrochloride tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS). Use of Sertraline Hydrochloride Tablets With Other MAOIs Such as Linezolid or Methylene Blue Do not start sertraline hydrochloride tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS). In some cases, a patient already receiving sertraline hydrochloride tablets therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, sertraline hydrochloride tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with sertraline hydrochloride tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS). The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with sertraline hydrochloride tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS). Special Populations Dosage for Hepatically Impaired Patients The use of sertraline in patients with liver disease should be approached with caution. The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied. If sertraline is administered to patients with liver impairment, a lower or less frequent dose should be used (see CLINICAL PHARMACOLOGY and PRECAUTIONS). Treatment of Pregnant Women During the Third Trimester Neonates exposed to sertraline hydrochloride tablets and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with sertraline hydrochloride tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.
Discontinuation of Treatment with Sertraline Hydrochloride Tablets
Symptoms associated with discontinuation of sertraline hydrochloride tablets and other SSRIs and SNRIs, have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
Amlodipine Besylate

Amlodipine Besylate

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF MINOCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS. Minocycline hydrochloride capsules may be taken with or without food (See CLINICAL PHARMACOLOGY.) Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration. The capsules should be swallowed whole. For Pediatric Patients Above 8 Years Of Age Usual pediatric dose: 4 mg/kg initially followed by 2 mg/kg every 12 hours, not to exceed the usual adult dose.

Adults

The usual dosage of minocycline hydrochloride capsules is 200 mg initially followed by 100 mg every 12 hours. Alternatively, if more frequent doses are preferred, two or four 50 mg capsules may be given initially followed by one 50 mg capsule 4 times daily.Uncomplicated gonococcal infections other than urethritis and anorectal infections in men: 200 mg initially, followed by 100 mg every 12 hours for a minimum of 4 days, with post-therapy cultures within 2 to 3 days.In the treatment of uncomplicated gonococcal urethritis in men, 100 mg every 12 hours for 5 days is recommended.For the treatment of syphilis, the usual dosage of minocycline hydrochloride should be administered over a period of 10 to 15 days. Close follow-up, including laboratory tests, is recommended.In the treatment of meningococcal carrier state, the recommended dosage is 100 mg every 12 hours for 5 days. Mycobacterium marinum infections: Although optimal doses have not been established, 100 mg every 12 hours for 6 to 8 weeks have been used successfully in a limited number of cases.Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis or Ureaplasma urealyticum: 100 mg orally, every 12 hours for at least 7 days.Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration.The pharmacokinetics of minocycline in patients with renal impairment (CLCR <80 mL/min) have not been fully characterized. Current data are insufficient to determine if a dosage adjustment is warranted. The total daily dosage should not exceed 200 mg in 24 hours. However, due to the anti-anabolic effect of tetracyclines, BUN and creatinine should be monitored. (See WARNINGS.)
Zidovudine

Zidovudine

2.1 Adults - Treatment of HIV-1 Infection

Oral Dosing The recommended oral dose of zidovudine capsules is 300 mg twice daily in combination with other antiretroviral agents.

2.2 Pediatric Patients (Aged 4 Weeks to Less than 18 Years)

Healthcare professionals should pay special attention to accurate calculation of the dose of zidovudine capsules, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.Prescribers should calculate the appropriate dose of zidovudine capsules for each child based on body weight (kg) and should not exceed the recommended adult dose.Before prescribing zidovudine capsules, children should be assessed for the ability to swallow capsules. If a child is unable to reliably swallow a zidovudine capsule, the zidovudine syrup formulation should be prescribed.The recommended oral dosage in pediatric patients aged 4 weeks to less than 18 years and weighing greater than or equal to 4 kg is provided in Table 1. Zidovudine syrup should be used to provide accurate dosage when whole capsules are not appropriate.
Table 1: Recommended Pediatric Oral Dosage of Zidovudine Capsules Body Weight (kg) Total Daily Dose Dosage Regimen and Dose Twice Daily Three Times Daily 4 to <9 24 mg/kg/day 12 mg/kg 8 mg/kg ≥9 to <30 18 mg/kg/day 9 mg/kg 6 mg/kg ≥30 600 mg/day 300 mg 200 mg
Alternatively, dosing for zidovudine capsules can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine capsules is 480 mg per m2 per day in divided doses (240 mg per m2 twice daily or 160 mg per m2 three times daily). In some cases the dose calculated by mg per kg will not be the same as that calculated by BSA.

2.3 Prevention of Maternal-Fetal HIV-1 Transmission

The recommended dosage regimen for administration to pregnant women (greater than 14 weeks of pregnancy) and their neonates is: Maternal Dosing 100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous zidovudine should be administered at 2 mg per kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg per kg per hour (total body weight) until clamping of the umbilical cord. Neonatal Dosing Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously. See Table 2.
Table 2. Recommended Neonatal Dosages of Zidovudine Route Total Daily Dose Dose and Dosage Regimen Oral 8 mg/kg/day 2 mg/kg every 6 hours Intravenous 6 mg/kg/day 1.5 mg/kg infused over 30 minutes, every 6 hours
2.4 Patients with Severe Anemia and/or Neutropenia

Significant anemia (hemoglobin less than 7.5 g per dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells per mm3 or reduction greater than 50% from baseline) may require a dose interruption until evidence of marrow recovery is observed [see Warnings and Precautions (5.1)]. In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoietin level and patient tolerance.

2.5 Patients with Renal Impairment

In patients maintained on hemodialysis or peritoneal dialysis or with creatinine clearance (CrCl) by Cockcroft-Gault less than 15 mL per min, the recommended oral dosage is 100 mg every 6 to 8 hours. [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.6 Patients with Hepatic Impairment

There are insufficient data to recommend dose adjustment of zidovudine capsules in patients with impaired hepatic function or liver cirrhosis. Frequent monitoring of hematologic toxicities is advised [see Use in Specific Populations (8.7)].
Zidovudine

Zidovudine

2.1 Adults - Treatment of HIV-1 Infection

Oral Dosing The recommended oral dose of zidovudine tablets is 300 mg twice daily in combination with other antiretroviral agents.

2.2 Pediatric Patients (Aged 4 Weeks to Less than 18 Years)

Healthcare professionals should pay special attention to accurate calculation of the dose of zidovudine tablets, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.Prescribers should calculate the appropriate dose of zidovudine tablets for each child based on body weight (kg) and should not exceed the recommended adult dose.Before prescribing zidovudine tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a zidovudine tablet, the zidovudine syrup formulation should be prescribed.The recommended oral dosage in pediatric patients aged 4 weeks to less than 18 years and weighing greater than or equal to 4 kg is provided in Table 1. Zidovudine syrup should be used to provide accurate dosage when whole tablets are not appropriate.
Table 1: Recommended Pediatric Oral Dosage of Zidovudine Tablets Body Weight (kg) Total Daily Dose Dosage Regimen and Dose Twice Daily Three Times Daily 4 to <9 24 mg/kg/day 12 mg/kg 8 mg/kg ≥9 to <30 18 mg/kg/day 9 mg/kg 6 mg/kg ≥30 600 mg/day 300 mg 200 mg
Alternatively, dosing for zidovudine tablets can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine tablets is 480 mg per m2 per day in divided doses (240 mg per m2 twice daily or 160 mg per m2 three times daily). In some cases the dose calculated by mg per kg will not be the same as that calculated by BSA.

2.3 Prevention of Maternal-Fetal HIV-1 Transmission

The recommended dosage regimen for administration to pregnant women (greater than 14 weeks of pregnancy) and their neonates is: Maternal Dosing 100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous zidovudine should be administered at 2 mg per kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg per kg per hour (total body weight) until clamping of the umbilical cord. Neonatal Dosing Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously. See Table 2.
Table 2. Recommended Neonatal Dosages of Zidovudine Route Total Daily Dose Dose and Dosage Regimen Oral 8 mg/kg/day 2 mg/kg every 6 hours Intravenous 6 mg/kg/day 1.5 mg/kg infused over 30 minutes, every 6 hours
2.4 Patients with Severe Anemia and/or Neutropenia

Significant anemia (hemoglobin less than 7.5 g per dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells per mm3 or reduction greater than 50% from baseline) may require a dose interruption until evidence of marrow recovery is observed [see Warnings and Precautions (5.1)]. In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoietin level and patient tolerance.

2.5 Patients with Renal Impairment

In patients maintained on hemodialysis or peritoneal dialysis or with creatinine clearance (CrCl) by Cockcroft-Gault less than 15 mL per min, the recommended oral dosage is 100 mg every 6 to 8 hours [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.6 Patients with Hepatic Impairment

There are insufficient data to recommend dose adjustment of zidovudine tablets in patients with impaired hepatic function or liver cirrhosis. Frequent monitoring of hematologic toxicities is advised [see Use in Specific Populations (8.7)].
Stimulant Laxative Ente...

Stimulant Laxative Enteric Coated

2.1 Dosage in Adult Patients

The dose of moxifloxacin is 400 mg (orally) once every 24 hours. The duration of therapy depends on the type of infection as described in Table 1.
Table 1: Dosage and Duration of Therapy in Adult Patients Type of Infectiona Dose Every 24 hours Durationb (days) a) Due to the designated pathogens [see Indications and Usage (1), for IV use, see Use in Specific Populations (8.5)]. b) Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. Acute Bacterial Sinusitis (1.1) 400 mg 10 Acute Bacterial Exacerbation of Chronic Bronchitis (1.2) 400 mg 5 Community Acquired Pneumonia 400 mg 7-14 Uncomplicated Skin and Skin Structure Infections (SSSI ) (1.4) 400 mg 7 Complicated SSSI (1.5) 400 mg 7-21 Complicated Intra-Abdominal Infections (1.6) 400 mg 5-14
Intravenous formulation is indicated when it offers a route of administration advantageous to the patient (for example, patient cannot tolerate an oral dosage form). When switching from intravenous to oral formulation, no dosage adjustment is necessary. Patients whose therapy is started with moxifloxacin hydrochloride IV may be switched to moxifloxacin hydrochloride tablets when clinically indicated at the discretion of the physician.

2.2 Drug Interactions with Multivalent Cations

Oral doses of moxifloxacin should be administered at least 4 hours before or 8 hours after products containing magnesium, aluminum, iron or zinc, including antacids, sucralfate, multivitamins and VIDEX® (didanosine) chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

2.3 Administration Instructions

Moxifloxacin hydrochloride tablets can be taken with or without food, drink fluids liberally.
Amoxicillin And Clavula...

Amoxicillin And Clavulanate Potassium

Amoxicillin and clavulanate potassium tablets may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium tablets are administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium tablets should be taken at the start of a meal.

2.1 Adults

The usual adult dose is one amoxicillin and clavulanate potassium tablet 500 mg/125 mg every 12 hours or one amoxicillin and clavulanate potassium tablet 250 mg/125 mg every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one amoxicillin and clavulanate potassium tablet 875 mg/125 mg every 12 hours or one amoxicillin and clavulanate potassium tablet 500 mg/125 mg every 8 hours. Adults who have difficulty swallowing may be given the 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet. The 200 mg/28.5 mg per 5 mL suspension or the 400 mg/57 mg per 5 mL suspension may be used in place of the 875 mg/125 mg tablet.Two amoxicillin and clavulanate potassium tablets 250 mg/125 mg should not be substituted for one amoxicillin and clavulanate potassium tablet 500 mg/125 mg. Since both the amoxicillin and clavulanate potassium tablets 250 mg/125 mg and 500 mg/125 mg contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250 mg/125 mg tablets are not equivalent to one amoxicillin and clavulanate potassium tablet 500 mg/125 mg.The amoxicillin and clavulanate potassium tablet 250 mg/125 mg and the 250 mg/62.5 mg chewable tablet should not be substituted for each other, as they are not interchangeable. The amoxicillin and clavulanate potassium tablet 250 mg/125 mg and the 250 mg/62.5 mg chewable tablet do not contain the same amount of clavulanic acid (as the potassium salt). The amoxicillin and clavulanate potassium tablet 250 mg/125 mg contains 125 mg of clavulanic acid, whereas the 250 mg/62.5 mg chewable tablet contains 62.5 mg of clavulanic acid.

2.2 Pediatric Patients

Based on the amoxicillin component, amoxicillin and clavulanate potassium tablets should be dosed as follows:Neonates and Infants Aged <12 weeks (<3 months): The recommended dose of amoxicillin and clavulanate potassium tablets is 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Experience with the 200 mg/28.5 mg per 5 mL formulation in this age group is limited, and thus, use of the 125 mg/31.25 mg per 5 mL oral suspension is recommended. Patients Aged 12 weeks (3 months) and Older: See dosing regimens provided in Table 1. The every 12 hour regimen is recommended as it is associated with significantly less diarrhea [see Clinical Studies (14.2)]. However, the every 12 hour suspension (200 mg/28.5 mg per 5 mL and 400 mg/57 mg per 5 mL) and chewable tablets (200 mg/28.5 mg and 400 mg/57 mg) contain aspartame and should not be used by phenylketonurics.
Table 1: Dosing in Patients Aged 12 weeks (3 months) and Older a Each strength of suspension of amoxicillin and clavulanate potassium is available as a chewable tablet for use by older children.b Duration of therapy studied and recommended for acute otitis media is 10 days. INFECTION DOSING REGIMEN Every 12 hours Every 8 hours 200 mg/28.5 mg per 5 mL or 400 mg/57 mg per 5 mL oral suspensiona 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL oral suspensiona Otitis mediab, sinusitis, lower respiratory tract infections, and more severe infections 45 mg/kg/day every 12 hours 40 mg/kg/day every 8 hours Less severe infections 25 mg/kg/day every 12 hours 20 mg/kg/day every 8 hours
Patients Weighing 40 kg or More: Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations.The amoxicillin and clavulanate potassium tablet 250 mg/125 mg should not be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the amoxicillin and clavulanate potassium tablet 250 mg/125 mg versus the amoxicillin and clavulanate potassium chewable tablet 250 mg/62.5 mg.

2.3 Patients with Renal Impairment

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should not receive the amoxicillin and clavulanate potassium tablets 875 mg/125 mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive amoxicillin and clavulanate potassium tablets 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive amoxicillin and clavulanate potassium tablets 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection.Hemodialysis patients should receive amoxicillin and clavulanate potassium tablets 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
Pramipexole Dihydrochlo...

Pramipexole Dihydrochloride

2.1 General Dosing Considerations

Pramipexole dihydrochloride tablets are taken orally, with or without food.If a significant interruption in therapy with pramipexole dihydrochloride tablets has occurred, re-titration of therapy may be warranted.

2.2 Dosing for Parkinson's Disease

In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects and orthostatic hypotension. Pramipexole dihydrochloride tablets should be titrated gradually in all patients. The dose should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth.Dosing in Patients with Normal Renal Function Initial Treatment Doses should be increased gradually from a starting dose of 0.375 mg/day given in three divided doses and should not be increased more frequently than every 5 to 7 days. A suggested ascending dosage schedule that was used in clinical studies is shown in Table 1:
Table 1 Ascending Dosage Schedule of Pramipexole Dihydrochloride tablets for Parkinson's Disease Week Dosage (mg) Total Daily Dose (mg) 1 0.125 three times a day 0.375 2 0.25 three times a day 0.75 3 0.5 three times a day 1.5 4 0.75 three times a day 2.25 5 1 three times a day 3 6 1.25 three times a day 3.75 7 1.5 three times a day 4.5
Maintenance Treatment Pramipexole dihydrochloride tablets were effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses three times per day with or without concomitant levodopa (approximately 800 mg/day).In a fixed-dose study in early Parkinson's disease patients, doses of 3 mg, 4.5 mg, and 6 mg per day of pramipexole dihydrochloride tablets were not shown to provide any significant benefit beyond that achieved at a daily dose of 1.5 mg/day. However, in the same fixed-dose study, the following adverse events were dose related: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence reported with pramipexole at a dose of 1.5 mg/day was comparable to placebo.When pramipexole dihydrochloride tablets are used in combination with levodopa, a reduction of the levodopa dosage should be considered. In a controlled study in advanced Parkinson's disease, the dosage of levodopa was reduced by an average of 27% from baseline.Dosing in Patients with Renal ImpairmentThe recommended dosing of pramipexole dihydrochloride tablets in Parkinson's disease patients with renal impairment is provided in Table 2.
Table 2 Dosing of Pramipexole Dihydrochloride tablets in Parkinson’s Disease Patients with Renal Impairment Renal Status Starting Dose (mg) Maximum Dose (mg) Normal to mild impairment (creatinine Cl > 50 mL/min) 0.125 three times a day 1.5 three times a day Moderate impairment (creatinine Cl = 30 to 50 mL/min) 0.125 twice a day 0.75 three times a day Severe impairment (creatinine Cl = 15 to <30 mL/min) 0.125 once a day 1.5 once a day Very severe impairment (creatinine Cl < 15 mL/min and hemodialysis patients) The use of pramipexole dihydrochloride tablets has not been adequately studied in this group of patients.
Discontinuation of Treatment Pramipexole dihydrochloride tablets may be tapered off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg. Thereafter, the dose may be reduced by 0.375 mg per day.
Fluticasone Propionate ...

Fluticasone Propionate Ointment

2.1 Dosage for Postherpetic Neuralgia

In adults with postherpetic neuralgia, gabapentin tablets may be initiated on Day 1 as a single 300 mg dose, on Day 2 as 600 mg/day (300 mg two times a day), and on Day 3 as 900 mg/day (300 mg three times a day). The dose can subsequently be titrated up as needed for pain relief to a dose of 1800 mg/day (600 mg three times a day). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range; however, in these clinical studies, the additional benefit of using doses greater than 1800 mg/day was not demonstrated.

2.2 Dosage for Epilepsy with Partial Onset Seizures

Patients 12 years of age and above

The starting dose is 300 mg three times a day. The recommended maintenance dose of gabapentin tablets is 300 mg to 600 mg three times a day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. Administer gabapentin tablets three times a day using 600 mg or 800 mg tablets. The maximum time between doses should not exceed 12 hours.

Pediatric Patients Age 3 to 11 years

The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the recommended maintenance dose reached by upward titration over a period of approximately 3 days. The recommended maintenance dose of gabapentin tablets in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses. The recommended maintenance dose of gabapentin tablets in patients 5 to 11 years of age is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

2.3 Dosage Adjustment in Patients with Renal Impairment

Dosage adjustment in patients 12 years of age and older with renal impairment or undergoing hemodialysis is recommended, as follows (see dosing recommendations above for effective doses in each indication):
TABLE 1. Gabapentin Tablets Dosage Based on Renal Function TID = Three times a day; BID = Two times a day; QD = Single daily dosea For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table. Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg) ≥ 60 900 to 3600 300 TID 400 TID 600 TID 800 TID 1200 TID >30 to 59 400 to 1400 200 BID 300 BID 400 BID 500 BID 700 BID >15 to 29 200 to 700 200 QD 300 QD 400 QD 500 QD 700 QD 15a 100 to 300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)b Hemodialysis 125b 150b 200b 250b 350b
Creatinine clearance (CLCr) is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance can be reasonably well estimated using the equation of Cockcroft and Gault:The use of gabapentin tablets in patients less than 12 years of age with compromised renal function has not been studied.

2.4 Dosage in Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.

2.5 Administration Information

Administer gabapentin tablets orally with or without food.Inform patients that, should they divide the scored 600 mg or 800 mg gabapentin tablet in order to administer a half-tablet, they should take the unused half-tablet as the next dose. Half-tablets not used within 28 days of dividing the scored tablet should be discarded.If the gabapentin tablets dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).
Amoxicillin

Amoxicillin

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

Except for gonorrhea, treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. In some infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.
Table 1. Dosing Recommendations for Adult and Pediatric Patients > 3 Months of Age Infection Severitya Usual Adult Dose Usual Dose for Children> 3 Monthsb a Dosing for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections. b The children’s dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations. Ear/Nose/Throat Skin/Skin Structure Genitourinary Tract Mild/Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours Lower Respiratory Tract Mild/Moderate or Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours Gonorrhea Acute, uncomplicated ano-genital and urethral infections in males and females 3 grams as single oral dose Prepubertal children: 50 mg/kg amoxicillin, combined with 25 mg/kg probenecid as a single dose. Note: Since probenecid is contraindicated in children under 2 years, do not use this regimen in children under 2 years of age.
2.2 Dosing in Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)

Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin tablets is 30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.

2.3 Dosing for H. pylori Infection

Triple Therapy: The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual Therapy: The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days. Please refer to clarithromycin and lansoprazole full prescribing information.

2.4 Dosing in Renal Impairment
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of < 30 mL/min should not receive a 875 mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
Amoxicillin And Clavula...

Amoxicillin And Clavulanate Potassium

Amoxicillin and clavulanate potassium for oral suspension may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium for oral suspension is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium for oral suspension should be taken at the start of a meal.

2.1 Adults

The usual adult dose is one amoxicillin and clavulanate potassium 500 mg/125 mg tablet every 12 hours or one amoxicillin and clavulanate potassium 250 mg/125 mg tablet every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one amoxicillin and clavulanate potassium 875 mg/125 mg tablet every 12 hours or one amoxicillin and clavulanate potassium 500 mg/125 mg tablet every 8 hours. Adults who have difficulty swallowing may be given the 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet. The 200 mg/28.5 mg per 5 mL suspension or the 400 mg/57 mg per 5 mL suspension may be used in place of the 875 mg/125 mg tablet.Two amoxicillin and clavulanate potassium 250 mg/125 mg tablets should not be substituted for one amoxicillin and clavulanate potassium 500 mg/125 mg tablet. Since both the amoxicillin and clavulanate potassium 250 mg/125 mg and 500 mg/125 mg tablets contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250 mg/125 mg tablets are not equivalent to one amoxicillin and clavulanate potassium 500 mg/125 mg tablet.The amoxicillin and clavulanate potassium 250 mg/125 mg tablet and the 250 mg/62.5 mg chewable tablet should not be substituted for each other, as they are not interchangeable. The amoxicillin and clavulanate potassium 250 mg/125 mg tablet and the 250 mg/62.5 mg chewable tablet do not contain the same amount of clavulanic acid (as the potassium salt). The amoxicillin and clavulanate potassium 250 mg/125 mg tablet contains 125 mg of clavulanic acid, whereas the 250 mg/62.5 mg chewable tablet contains 62.5 mg of clavulanic acid.

2.2 Pediatric Patients

Based on the amoxicillin component, amoxicillin and clavulanate potassium for oral suspension should be dosed as follows: Neonates and Infants Aged <12 weeks (<3 months): The recommended dose of amoxicillin and clavulanate potassium for oral suspension is 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Experience with the 200 mg/28.5 mg per 5 mL formulation in this age group is limited, and thus, use of the 125 mg/31.25 mg per 5 mL oral suspension is recommended. Patients Aged 12 weeks (3 months) and Older: See dosing regimens provided in Table 1. The every 12 hour regimen is recommended as it is associated with significantly less diarrhea [see Clinical Studies (14.2)]. However, the every 12 hour suspension (200 mg/28.5 mg per 5 mL and 400 mg/57 mg per 5 mL) and chewable tablets (200 mg/28.5 mg and 400 mg/57 mg) contain aspartame and should not be used by phenylketonurics [see Warnings and Precautions (5.6)].

Table 1: Dosing in Patients Aged 12 weeks (3 months) and Older a Each strength of suspension of amoxicillin and clavulanate potassium is available as a chewable tablet for use by older children. b Duration of therapy studied and recommended for acute otitis media is 10 days. INFECTION DOSING REGIMEN Every 12 hours Every 8 hours 200 mg/28.5 mg per 5 mL or 400 mg/57 mg per 5 mL oral suspensiona 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL oral suspensiona Otitis mediab, sinusitis, lower respiratory tract infections, and more severe infections 45 mg/kg/day every 12 hours 40 mg/kg/day every 8 hours Less severe infections 25 mg/kg/day every 12 hours 20 mg/kg/day every 8 hours
Patients Weighing 40 kg or More: Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations.The amoxicillin and clavulanate potassium 250 mg/125 mg tablet should not be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the amoxicillin and clavulanate potassium 250 mg/125 mg tablet versus the amoxicillin and clavulanate potassium 250 mg/62.5 mg chewable tablet.

2.3 Patients with Renal Impairment

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should not receive the dose of amoxicillin and clavulanate potassium tablets 875 mg/125 mg. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive amoxicillin and clavulanate potassium tablets 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive amoxicillin and clavulanate potassium tablets 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection.Hemodialysis patients should receive amoxicillin and clavulanate potassium tablets 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

2.4 Directions for Mixing Oral Suspension

Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution (see Table 2 below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Table 2: Amount of Water for Mixing Oral Suspension Strength Bottle Size Amount of Water for Reconstitution Contents of Each Teaspoonful (5 mL) 200 mg/28.5 mg per 5 mL 50 mL75 mL100 mL 52 mL73 mL98 mL 200 mg amoxicillin and 28.5 mg of clavulanic acid as the potassium salt 400 mg/57 mg per 5 mL 50 mL75 mL100 mL 49 mL70 mL94 mL 400 mg amoxicillin and 57 mg of clavulanic acid as the potassium salt
Note: Shake oral suspension well before using. Reconstituted suspension must be stored under refrigeration and discarded after 10 days.
Cefprozil

Cefprozil

Cefprozil is administered orally.
Population/Infection Dosage(mg) Duration (days) a In the treatment of infections due to Streptococcus pyogenes, cefprozil should be administered for at least 10 days.b Not to exceed recommended adult doses. ADULTS (13 years and older) UPPER RESPIRATORY TRACT Pharyngitis/Tonsillitis 500 q24h 10a Acute Sinusitis (For moderate to severe infections, the higher dose should be used) 250 q12h or500 q12h 10 LOWER RESPIRATORY TRACT Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis 500 q12h 10 SKIN AND SKIN STRUCTURE Uncomplicated Skin and Skin Structure Infections 250 q12h or500 q24h or500 q12h 10 CHILDREN (2 years to 12 years) UPPER RESPIRATORY TRACTb Pharyngitis/Tonsillitis 7.5 mg/kg q12h 10a SKIN AND SKIN STRUCTUREb Uncomplicated Skin and Skin Structure Infections 20 mg/kg q24h 10 INFANTS & CHILDREN (6 months to 12 years) UPPER RESPIRATORY TRACTb Otitis Media (See INDICATIONS AND USAGE and CLINICAL STUDIES) 15 mg/kg q12h 10 Acute Sinusitis (For moderate to severe infections, the higher dose should be used) 7.5 mg/kg q12h or 15 mg/kg q12h 10
Renal Impairment

Cefprozil may be administered to patients with impaired renal function. The following dosage schedule should be used.
Creatinine Clearance(mL/min) Dosage (mg) Dosing Interval * Cefprozil is in part removed by hemodialysis; therefore, cefprozil should be administered after the completion of hemodialysis. 30–1200–29* standard50% of standard standardstandard
Hepatic Impairment

No dosage adjustment is necessary for patients with impaired hepatic function.
Folic Acid

Folic Acid

Famciclovir tablets may be taken with or without food.

2.1 Dosing Recommendation in Immunocompetent Adult Patients

Herpes labialis (cold sores): The recommended dosage of famciclovir tablets for the treatment of recurrent herpes labialis is 1500 mg as a single dose. Therapy should be initiated at the first sign or symptom of herpes labialis (e.g., tingling, itching, burning, pain, or lesion). Genital herpes: Recurrent episodes: The recommended dosage of famciclovir tablets for the treatment of recurrent episodes of genital herpes is 1000 mg twice daily for 1 day. Therapy should be initiated at the first sign or symptom of a recurrent episode (e.g., tingling, itching, burning, pain, or lesion). Suppressive therapy: The recommended dosage of famciclovir tablets for chronic suppressive therapy of recurrent episodes of genital herpes is 250 mg twice daily.

2.2 Dosing Recommendation in HIV-Infected Adult Patients

Recurrent orolabial or genital herpes: The recommended dosage of famciclovir tablets for the treatment of recurrent orolabial or genital herpes in HIV-infected patients is 500 mg twice daily for 7 days. Therapy should be initiated at the first sign or symptom of a recurrent episode (e.g., tingling, itching, burning, pain, or lesion).

2.3 Dosing Recommendation in Patients with Renal Impairment

Dosage recommendations for adult patients with renal impairment are provided in Table 1 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Table 1 Dosage Recommendations for Adult Patients with Renal Impairment Indication and Normal Dosage Regimen Creatinine Clearance (mL/min) Adjusted Dosage Regimen Dose (mg) Dosing Interval *Hemodialysis Single-Day Dosing Regimens Recurrent Genital Herpes 1000 mg every 12 hours for 1 day ≥60 1000 every 12 hours for 1 day 40 to 59 500 every 12 hours for 1 day 20 to 39 500 single dose <20 250 single dose HD* 250 single dose following dialysis Recurrent Herpes Labialis 1500 mg single dose ≥60 1500 single dose 40 to 59 750 single dose 20 to 39 500 single dose <20 250 single dose HD* 250 single dose following dialysis Multiple-Day Dosing Regimens Suppression of Recurrent Genital Herpes 250 mg every 12 hours ≥40 250 every 12 hours 20 to 39 125 every 12 hours <20 125 every 24 hours HD* 125 following each dialysis Recurrent Orolabial or Genital Herpes in HIV-Infected Patients 500 mg every 12 hours ≥40 500 every 12 hours 20 to 39 500 every 24 hours <20 250 every 24 hours HD* 250 following each dialysis
Multi-symptom Non-aspir...

Multi-symptom Non-aspirin Cold Nighttime

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. In some infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.
Table 1. Dosing Recommendations for Adult and Pediatric Patients > 3 Months of Age Infection Severitya Usual Adult Dose Usual Dose for Children > 3 Monthsb a Dosing for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections.b The children’s dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations. Ear/Nose/Throat Skin/Skin Structure Genitourinary Tract Mild/Moderate 500 mg every 12 hours or250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours Lower Respiratory Tract Mild/Moderate or Severe 875 mg every 12 hours or500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
2.2 Dosing in Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)

Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin for oral suspension is

30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.

2.3 Dosing for H. pylori Infection

Triple therapy:The recommended adult oral dose is 1 gram amoxicillin for oral suspension, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days.Dual therapy:The recommended adult oral dose is 1 gram amoxicillin for oral suspension and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days.Please refer to clarithromycin and lansoprazole full prescribing information.

2.4 Dosing in Renal Impairment
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of < 30 mL/min. should not receive a 875 mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
2.5 Directions for Mixing Oral Suspension

Tap bottle until all powder flows freely. Add approximately 1/3 of the total amount of water for reconstitution (see Table 2) and shake vigorously to wet powder. Add remainder of the water and again shake vigorously.
Table 2. Amount of Water for Mixing Oral Suspension Strength Bottle Size Amount of Water Required for Reconstitution Oral Suspension 200 mg/5 mL 50 mL 35 mL 75 mL 52 mL 100 mL 69 mL Oral Suspension 400 mg/5 mL 50 mL 35 mL 75 mL 52 mL 100 mL 69 mL
After reconstitution, the required amount of suspension should be placed directly on the child’s tongue for swallowing. Alternate means of administration are to add the required amount of suspension to formula, milk, fruit juice, water, ginger ale, or cold drinks. These preparations should then be taken immediately. NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING. Keep bottle tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration is preferable, but not required.
Zolpidem Tartrate

Zolpidem Tartrate

2.1 Dosage in Adults

Use the lowest effective dose for the patient. The recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening. If the 5 mg dose is not effective, the dose can be increased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [see Warnings and Precautions (5.1)]. The total dose of zolpidem tartrate tablets should not exceed 10 mg once daily immediately before bedtime.The recommended initial doses for women and men are different because zolpidem clearance is lower in women.

2.2 Special Populations

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. Patients with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose of zolpidem tartrate tablets in both of these patient populations is 5 mg once daily immediately before bedtime [see Warnings and Precautions (5.1); Use in Specific Populations (8.5)].

2.3 Use with CNS Depressants

Dosage adjustment may be necessary when zolpidem tartrate tablets are combined with other CNS depressant drugs because of the potentially additive effects [see Warnings and Precautions (5.1)].

2.4 Administration

The effect of zolpidem tartrate tablets may be slowed by ingestion with or immediately after a meal.
Carisoprodol

Carisoprodol

The recommended dose of carisoprodol tablets is 350 mg three times a day and at bedtime. The recommended maximum duration of carisoprodol tablets use is up to two or three weeks.
Cefprozil

Cefprozil

Cefprozil tablets are administered orally.
Population/Infection Dosage(mg) Duration(days) a In the treatment of infections due to Streptococcus pyogenes, cefprozil should be administered for at least 10 days.b Not to exceed recommended adult doses. ADULTS (13 years and older) UPPER RESPIRATORY TRACT Pharyngitis/Tonsillitis 500 q24h 10a Acute Sinusitis (For moderate to severe infections, the higher dose should be used) 250 q12h or500 q12h 10 LOWER RESPIRATORY TRACT Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis 500 q12h 10 SKIN AND SKIN STRUCTURE Uncomplicated Skin and Skin Structure Infections 250 q12h or500 q24h or500 q12h 10 CHILDREN (2 years–12 years) UPPER RESPIRATORY TRACTb Pharyngitis/Tonsillitis 7.5 mg/kg q12h 10a SKIN AND SKIN STRUCTUREb Uncomplicated Skin and Skin Structure Infections 20 mg/kg q24h 10 INFANTS & CHILDREN (6 months–12 years) UPPER RESPIRATORY TRACTb Otitis Media (See INDICATIONS AND USAGE and CLINICAL STUDIES) 15 mg/kg q12h 10 Acute Sinusitis (For moderate to severe infections, the higher dose should be used) 7.5 mg/kg q12h or15 mg/kg q12h 10
Renal Impairment

Cefprozil may be administered to patients with impaired renal function. The following dosage schedule should be used.
Creatinine Clearance(mL/min) Dosage (mg) Dosing Interval * Cefprozil is in part removed by hemodialysis; therefore, cefprozil should be administered after the completion of hemodialysis. 30–1200–29* standard50% of standard standard standard
Hepatic Impairment

No dosage adjustment is necessary for patients with impaired hepatic function.
Stavudine

Stavudine

The interval between doses of stavudine capsules should be 12 hours. Stavudine capsules may be taken with or without food.

2.1 Recommended Adult Dosage

The recommended adult dosage is based on body weight as follows:
For patients weighing less than 60 kg: 30 mg every 12 hours. For patients weighing at least 60 kg: 40 mg every 12 hours.
2.2 Recommended Pediatric Dosage
For newborns from birth to 13 days old: 0.5 mg/kg given every 12 hours. For pediatric patients at least 14 days old and weighing less than 30 kg: 1 mg/kg given every 12 hours. For pediatric patients weighing at least 30 kg: use the recommended adult dosage.
2.3 Dosage Adjustment

Renal Impairment Adult Patients: Stavudine capsules may be administered to adult patients with impaired renal function with an adjustment in dosage as shown in Table 1.
Table 1: Recommended Dosage Adjustment for Adult Patients with Renal Impairment Creatinine Clearance(mL/min) Recommended Stavudine Capsules Doseby Patient Weight at least 60 kg less than 60 kg * Administered after the completion of hemodialysis on dialysis days and at the same time of day on non-dialysis days. greater than 50 40 mg every 12 hours 30 mg every 12 hours 26–50 20 mg every 12 hours 15 mg every 12 hours 10–25 20 mg every 24 hours 15 mg every 24 hours Hemodialysis 20 mg every 24 hours* 15 mg every 24 hours*
Pediatric Patients: Since urinary excretion is also a major route of elimination of stavudine in pediatric patients, the clearance of stavudine may be altered in children with renal impairment. There are insufficient data to recommend a specific dose adjustment of stavudine capsules in this patient population.
Tramadol Hydrochloride

Tramadol Hydrochloride

2.1 Adult Hypertension

The recommended starting dose of valsartan tablets is 80 mg or 160 mg once daily when used as monotherapy in patients who are not volume-depleted. Patients requiring greater reductions may be started at the higher dose. Valsartan tablets may be used over a dose range of 80 mg to 320 mg daily, administered once a day. The antihypertensive effect is substantially present within 2 weeks and maximal reduction is generally attained after 4 weeks. If additional antihypertensive effect is required over the starting dose range, the dose may be increased to a maximum of 320 mg or a diuretic may be added. Addition of a diuretic has a greater effect than dose increases beyond 80 mg. No initial dosage adjustment is required for elderly patients, for patients with mild or moderate renal impairment, or for patients with mild or moderate liver insufficiency. Care should be exercised with dosing of valsartan tablets in patients with hepatic or severe renal impairment. Valsartan tablets may be administered with other antihypertensive agents. Valsartan tablets may be administered with or without food.

2.2 Pediatric Hypertension 6 to 16 Years of Age

For children who can swallow tablets, the usual recommended starting dose is 1.3 mg/kg once daily (up to 40 mg total). The dosage should be adjusted according to blood pressure response. Doses higher than 2.7 mg/kg (up to 160 mg) once daily have not been studied in pediatric patients 6 to 16 years old. For children who cannot swallow tablets, or children for whom the calculated dosage (mg/kg) does not correspond to the available tablet strengths of valsartan, the use of a suspension is recommended. Follow the suspension preparation instructions below (see Preparation of Suspension) to administer valsartan as a suspension. When the suspension is replaced by a tablet, the dose of valsartan may have to be increased. The exposure to valsartan with the suspension is 1.6 times greater than with the tablet. No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate <30 mL/min/1.73 m2 [see Pediatric Use (8.4)]. Valsartan tablets are not recommended for patients <6 years old [see Adverse Reactions (6.1), Clinical Studies (14.1)]. Preparation of Suspension (for 160 mL of a 4 mg/mL suspension) Add 80 mL of Ora-Plus®* oral suspending vehicle to an amber glass bottle containing 8 valsartan 80 mg tablets, and shake for a minimum of 2 minutes. Allow the suspension to stand for a minimum of 1 hour. After the standing time, shake the suspension for a minimum of 1 additional minute. Add 80 mL of Ora-Sweet SF®* oral sweetening vehicle to the bottle and shake the suspension for at least 10 seconds to disperse the ingredients. The suspension is homogenous and can be stored for either up to 30 days at room temperature (below 30°C/86°F) or up to 75 days at refrigerated conditions (2 to 8°C/35 to 46°F) in the glass bottle with a child-resistant screw-cap closure. Shake the bottle well (at least 10 seconds) prior to dispensing the suspension. *Ora-Sweet SF® and Ora-Plus® are registered trademarks of Paddock Laboratories, Inc.

2.3 Heart Failure

The recommended starting dose of valsartan tablets is 40 mg twice daily. Uptitration to 80 mg and 160 mg twice daily should be done to the highest dose, as tolerated by the patient. Consideration should be given to reducing the dose of concomitant diuretics. The maximum daily dose administered in clinical trials is 320 mg in divided doses.
Ranitidine Hydrochlorid...

Ranitidine Hydrochloride

2.1 Dosing in Mild to Moderate Alzheimer's Disease

The recommended starting dosage of donepezil hydrochloride tablets is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of donepezil hydrochloride tablets in patients with mild to moderate Alzheimer’s disease is 10 mg per day. A dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks.

2.2 Dosing in Moderate to Severe Alzheimer's Disease

The recommended starting dosage of donepezil hydrochloride tablets is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of donepezil hydrochloride tablets in patients with moderate to severe Alzheimer’s disease is 23 mg per day. A dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks. A dose of 23 mg per day should not be administered until patients have been on a daily dose of 10 mg for at least 3 months.

2.3 Administration Information

Donepezil hydrochloride tablets should be taken in the evening, just prior to retiring. Donepezil hydrochloride tablets can be taken with or without food.

The donepezil hydrochloride 23 mg tablet should not be split, crushed, or chewed.
Meloxicam

Meloxicam

2.1 General Instructions

Carefully consider the potential benefits and risks of meloxicam tablets and other treatment options before deciding to use meloxicam tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5.4)].After observing the response to initial therapy with meloxicam tablets, adjust the dose to suit an individual patient's needs.In adults, the maximum recommended daily oral dose of meloxicam is 15 mg regardless of formulation. In patients with hemodialysis, a maximum daily dosage of 7.5 mg is recommended [see Warnings and Precautions (5.6), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].Meloxicam tablets may be taken without regard to timing of meals.

2.2 Osteoarthritis

For the relief of the signs and symptoms of osteoarthritis the recommended starting and maintenance oral dose of meloxicam tablets is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.

2.3 Rheumatoid Arthritis

For the relief of the signs and symptoms of rheumatoid arthritis, the recommended starting and maintenance oral dose of meloxicam tablets is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.

2.4 Juvenile Rheumatoid Arthritis (JRA) Pauciarticular and Polyarticular Course

For the treatment of juvenile rheumatoid arthritis, the recommended oral dose of meloxicam is 0.125 mg/kg once daily up to a maximum of 7.5 mg. There was no additional benefit demonstrated by increasing the dose above 0.125 mg/kg once daily in these clinical trials.
Cephalexin

Cephalexin

Cephalexin capsules are administered orally. Adults — The adult dosage ranges from 1 to 4 g daily in divided doses. The usual adult dose is 250 mg every 6 hours. For the following infections, a dosage of 500 mg may be administered every 12 hours: streptococcal pharyngitis, skin and skin structure infections, and uncomplicated cystitis in patients over 15 years of age. Cystitis therapy should be continued for 7 to 14 days. For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of cephalexin greater than 4 g are required, parenteral cephalosporins, in appropriate doses, should be considered. Pediatric Patients — The usual recommended daily dosage for pediatric patients is 25 to 50 mg/kg in divided doses. For streptococcal pharyngitis in patients over 1 year of age and for skin and skin structure infections, the total daily dose may be divided and administered every 12 hours.In severe infections, the dosage may be doubled.In the therapy of otitis media, clinical studies have shown that a dosage of 75 to 100 mg/kg/day in 4 divided doses is required.In the treatment of β-hemolytic streptococcal infections, a therapeutic dosage of cephalexin should be administered for at least 10 days.
Galantamine

Galantamine

2.2 Galantamine Immediate-Release Tablets

The dosage of galantamine tablets shown to be effective in controlled clinical trials is 16 to 32 mg/day given as twice daily dosing. As the dosage of 32 mg/day is less well tolerated than lower dosages and does not provide increased effectiveness, the recommended dosage range is 16 to 24 mg/day given twice daily. The dosage of 24 mg/day did not provide a statistically significant greater clinical benefit than 16 mg/day. It is possible, however, that a daily dosage of 24 mg of galantamine tablets might provide additional benefit for some patients.The recommended starting dosage of galantamine tablets is 4 mg twice a day (8 mg/day). The dosage should be increased to the initial maintenance dosage of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day).Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.Galantamine tablets should be administered twice a day, preferably with morning and evening meals.Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for more than three days, the patient should be restarted at the lowest dosage and the dosage escalated to the current dose.The abrupt withdrawal of galantamine tablets in those patients who had been receiving dosages in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same dosages of that drug. The beneficial effects of galantamine tablets are lost, however, when the drug is discontinued.

2.3 Dosage in Patients with Hepatic Impairment

In patients with moderate hepatic impairment (Child-Pugh score of 7 to 9), the dosage should generally not exceed 16 mg/day. The use of galantamine tablets in patients with severe hepatic impairment (Child-Pugh score of 10 to 15) is not recommended [see Clinical Pharmacology (12.3)].

2.4 Dosage in Patients with Renal Impairment

In patients with creatinine clearance of 9 to 59 mL/min, the dosage should generally not exceed 16 mg/day. In patients with creatinine clearance less than 9 mL/min, the use of and galantamine tablets is not recommended [see Clinical Pharmacology (12.3)].
Sulfamethoxazole And Tr...

Sulfamethoxazole And Trimethoprim Suspension

Sulfamethoxazole and trimethoprim oral suspension is contraindicated in pediatric patients less than 2 months of age. Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children AdultsThe usual adult dosage in the treatment of urinary tract infections is four teaspoonfuls (20 mL) sulfamethoxazole and trimethoprim oral suspension every 12 hours for 10 to 14 days. An identical daily dosage is used for 5 days in the treatment of shigellosis.ChildrenThe recommended dose for children with urinary tract infections or acute otitis media is 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. The following table is a guideline for the attainment of this dosage: Children 2 months of age or older:
Weight Dose–every 12 hours lb kg Teaspoonfuls 22 10 1 (5 mL) 44 20 2 (10 mL) 66 30 3 (15 mL) 88 40 4 (20 mL)
For Patients with Impaired Renal Function When renal function is impaired, a reduced dosage should be employed using the following table:
Creatinine Clearance (mL/min) Recommended Dosage Regimen Above 30 Usual standard regimen 15 to 30 ½ the usual regimen Below 15 Use not recommended
Acute Exacerbations of Chronic Bronchitis in Adults The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is four teaspoonfuls (20 mL) sulfamethoxazole and trimethoprim oral suspension every 12 hours for 14 days.Pneumocystis Jiroveci PneumoniaTreatment Adults and Children The recommended dosage for treatment of patients with documented Pneumocystis jiroveci pneumonia is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days.11 The following table is a guideline for the upper limit of this dosage:
Weight Dose–every 6 hours lb kg Teaspoonfuls 18 8 1 (5 mL) 35 16 2 (10 mL) 53 24 3 (15 mL) 70 32 4 (20 mL) 88 40 5 (25 mL) 106 48 6 (30 mL) 141 64 8 (40 mL) 176 80 10 (50 mL)
For the lower limit dose (75 mg/kg sulfamethoxazole and 15 mg/kg trimethoprim per 24 hours) administer 75% of the dose in the above table.Prophylaxis Adults The recommended dosage for prophylaxis in adults is four teaspoonfuls (20 mL) of the suspension daily.12 Children For children, the recommended dose is 750 mg/m2/day sulfamethoxazole with 150 mg/m2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week. The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim.13 The following table is a guideline for the attainment of this dosage in children:
Body Surface Area Dose–every 12 hours (m2) Teaspoonfuls 0.26 ½ (2.5 mL) 0.53 1 (5 mL) 1.06 2 (10 mL)
Traveler’s Diarrhea in Adults For the treatment of traveler’s diarrhea, the usual adult dosage is four teaspoonfuls (20 mL) of the suspension every 12 hours for 5 days.
Cefpodoxime Proxetil

Cefpodoxime Proxetil

(See INDICATIONS AND USAGE for indicated pathogens.) FILM-COATED TABLETS: Cefpodoxime proxetil tablets should be administered orally with food to enhance absorption. (See CLINICAL PHARMACOLOGY.)The recommended dosages, durations of treatment, and applicable patient population are as described in the following chart:
Adults and Adolescents (age 12 years and older): Type of Infection Total DailyDose Dose Frequency Duration    Pharyngitis and/or tonsillitis 200 mg 100 mg Q 12 hours 5 to 10 days    Acute community-acquired pneumonia 400 mg 200 mg Q 12 hours 14 days    Acute bacterial exacerbations of chronic bronchitis 400 mg 200 mg Q 12 hours 10 days    Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women) 200 mg single dose    Skin and skin structure 800 mg 400 mg Q 12 hours 7 to 14 days    Acute maxillary sinusitis 400 mg 200 mg Q 12 hours 10 days    Uncomplicated urinary tract infection 200 mg 100 mg Q 12 hours 7 days
GRANULES FOR ORAL SUSPENSION: Cefpodoxime proxetil oral suspension may be given without regard to food. The recommended dosages, durations of treatment, and applicable patient populations are as described in the following chart:
Adults and Adolescents (age 12 years and older): Type of Infection Total Daily Dose Dose Frequency Duration    Pharyngitis and/or tonsillitis 200 mg 100 mg Q 12 hours 5 to 10 days    Acute community-acquired pneumonia 400 mg 200 mg Q 12 hours 14 days    Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women) 200 mg single dose    Skin and skin structure 800 mg 400 mg Q 12 hours 7 to 14 days    Acute maxillary sinusitis 400 mg 200 mg Q 12 hours 10 days    Uncomplicated urinary tract infection 200 mg 100 mg Q 12 hours 7 days Infants and Pediatric Patients (age 2 months through 12 years): Type of Infection Total Daily Dose Dose Frequency Duration    Acute otitis media 10 mg/kg/day(Max 400 mg/day) 5 mg/kg Q 12 h(Max 200 mg/dose) 5 days    Pharyngitis and/or tonsillitis 10 mg/kg/day(Max 200 mg/day) 5 mg/kg/dose Q 12 h(Max 100 mg/dose) 5 to 10 days    Acute maxillary sinusitis 10 mg/kg/day(Max 400 mg/day) 5 mg/kg Q 12 hours(Max 200 mg/dose) 10 days
Patients with Renal Dysfunction: For patients with severe renal impairment (<30 mL/min creatinine clearance), the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to estimate creatinine clearance (mL/min). For this estimate to be valid, the serum creatinine level should represent a steady state of renal function.Males:                                      Weight (kg) x (140 - age) (mL/min)                                 72 x serum creatinine (mg/100 mL)Females:                                  0.85 x above value(mL/min)Patients with Cirrhosis: Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) are similar to those in healthy subjects. Dose adjustment is not necessary in this population.
Glucovance

Glucovance

As individual monotherapy, quinapril is an effective treatment of hypertension in once-daily doses of 10 mg to 80 mg and hydrochlorothiazide is effective in doses of 12.5 mg to 50 mg. In clinical trials of quinapril/hydrochlorothiazide combination therapy using quinapril doses of 2.5 mg to 40 mg and hydrochlorothiazide doses of 6.25 mg to 25 mg, the antihypertensive effects increased with increasing dose of either component.The side effects (see WARNINGS) of quinapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of quinapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but regimens that combine low doses of hydrochlorothiazide with quinapril produce minimal effects on serum potassium. In clinical trials of quinapril and hydrochlorothiazide tablets, the average change in serum potassium was near zero in subjects who received HCTZ 6.25 mg in the combination, and the average subject who received 10 mg to 40 mg/12.5 mg to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy.To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy. Therapy Guided by Clinical Effect Patients whose blood pressures are not adequately controlled with quinapril monotherapy may instead be given quinapril and hydrochlorothiazide tablets 10 mg/12.5 mg or 20 mg/12.5 mg. Further increases of either or both components could depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve blood pressure control with less electrolyte disturbance if they are switched to quinapril and hydrochlorothiazide tablets 10 mg/12.5 mg or 20 mg/12.5 mg. Replacement Therapy For convenience, patients who are adequately treated with 20 mg of quinapril and 25 mg of hydrochlorothiazide and experience no significant electrolyte disturbances may instead wish to receive quinapril and hydrochlorothiazide tablets 20 mg/25 mg. Use in Renal Impairment Regimens of therapy with quinapril and hydrochlorothiazide tablets need not take account of renal function as long as the patient’s creatinine clearance is >30 mL/min/ 1.73 m2 (serum creatinine roughly ≤3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides. Therefore, quinapril and hydrochlorothiazide tablets are not recommended for use in these patients.
Tizanidine

Tizanidine

2.1 Adults

The usual initial antihypertensive oral dose of amlodipine besylate tablets is 5 mg once daily, and the maximum dose is 10 mg once daily.Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding amlodipine besylate tablets to other antihypertensive therapy.Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently. Angina: The recommended dose for chronic stable or vasospastic angina is 5 to 10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect. Coronary artery disease: The recommended dose range for patients with coronary artery disease is 5 to 10 mg once daily. In clinical studies, the majority of patients required 10 mg [see Clinical Studies (14.4)].

2.2 Children

The effective antihypertensive oral dose in pediatric patients ages 6 to 17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients [see Clinical Pharmacology (12.4), Clinical Studies (14.1)].
Abacavir

Abacavir

A Medication Guide and Warning Card that provide information about recognition of hypersensitivity reactions should be dispensed with each new prescription and refill. Abacavir tablets may be taken with or without food.
2.1 Adult Patients

The recommended oral dose of abacavir tablets for adults is 600 mg daily, administered as either 300 mg twice daily or 600 mg once daily, in combination with other antiretroviral agents.

2.2 Pediatric Patients

Abacavir tablets are available as scored tablet for HIV-1-infected pediatric patients weighing greater than or equal to 14 kg for whom a solid dosage form is appropriate. Before prescribing abacavir tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow abacavir tablets, the oral solution formulation should be prescribed. The recommended oral dosage of abacavir tablets for HIV-1-infected pediatric patients is presented in Table 1.
Table 1. Dosing Recommendations for Abacavir Scored Tablets in Pediatric Patients Weight (kg) Twice-daily Dosing Regimen AM Dose PM Dose Total Daily Dose 14 to <20 ½ tablet (150 mg) ½ tablet (150 mg) 300 mg >20 to <25 ½ tablet (150 mg) 1 tablet (300 mg) 450 mg ≥25 1 tablet (300 mg) 1 tablet (300 mg) 600 mg
Additional pediatric use information for patients aged 3 months and above is approved for ViiV Healthcare Company’s ZIAGEN® (abacavir sulfate) tablets. However, due to ViiV Healthcare Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.3 Patients with Hepatic Impairment

The recommended dose of abacavir tablets in patients with mild hepatic impairment (Child-Pugh score 5 to 6) is 200 mg twice daily. To enable dose reduction, abacavir sulfate oral solution (10 mL twice daily) should be used for the treatment of these patients. The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate to severe hepatic impairment; therefore, abacavir tablets are contraindicated in these patients.
Berkley And Jensen Omep...

Berkley And Jensen Omeprazole

2.1 Schizophrenia

Adults Dose Selection — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg initially, with a target dose of 10 mg/day within several days. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended.Efficacy in schizophrenia was demonstrated in a dose range of 10 to 15 mg/day in clinical trials. However, doses above 10 mg/day were not demonstrated to be more efficacious than the 10 mg/day dose. An increase to a dose greater than the target dose of 10 mg/day (i.e., to a dose of 15 mg/day or greater) is recommended only after clinical assessment. Olanzapine is not indicated for use in doses above 20 mg/day. Dosing in Special Populations — The recommended starting dose is 5 mg in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients ≥65 years of age), or who may be more pharmacodynamically sensitive to olanzapine [see Warnings and Precautions (5.12), Drug Interactions (7), and Clinical Pharmacology (12.3)]. When indicated, dose escalation should be performed with caution in these patients. Maintenance Treatment — The effectiveness of oral olanzapine, 10 mg/day to 20 mg/day, in maintaining treatment response in schizophrenic patients who had been stable on olanzapine tablets for approximately 8 weeks and were then followed for relapse has been demonstrated in a placebo-controlled trial [see Clinical Studies (14.1)]. The physician who elects to use olanzapine tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.Adolescents Dose Selection — Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with schizophrenia was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 12.5 mg/day (mean dose of 11.1 mg/day). When dosage adjustments are necessary, dose increments/decrements of 2.5 or 5 mg are recommended.The safety and effectiveness of doses above 20 mg/day have not been evaluated in clinical trials [see Clinical Studies (14.1)]. Maintenance Treatment — The efficacy of olanzapine tablets for the maintenance treatment of schizophrenia in the adolescent population has not been systematically evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.2 Bipolar I Disorder (Manic or Mixed Episodes)

Adults Dose Selection for Monotherapy — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 10 or 15 mg. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended.Short-term (3 to 4 weeks) antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials. The safety of doses above 20 mg/day has not been evaluated in clinical trials [see Clinical Studies (14.2)]. Maintenance Monotherapy — The benefit of maintaining bipolar I patients on monotherapy with oral olanzapine tablets at a dose of 5 to 20 mg/day, after achieving a responder status for an average duration of 2 weeks, was demonstrated in a controlled trial [see Clinical Studies (14.2)]. The physician who elects to use olanzapine tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient. Dose Selection for Adjunctive Treatment — When administered as adjunctive treatment to lithium or valproate, oral olanzapine dosing should generally begin with 10 mg once-a-day without regard to meals.Antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials [see Clinical Studies (14.2)]. The safety of doses above 20 mg/day has not been evaluated in clinical trials. Adolescents Dose Selection — Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with bipolar I disorder (manic or mixed episodes) was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 10.7 mg/day (mean dose of 8.9 mg/day). When dosage adjustments are necessary, dose increments/decrements of 2.5 or 5 mg are recommended.The safety and effectiveness of doses above 20 mg/day have not been evaluated in clinical trials [see Clinical Studies (14.2)]. Maintenance Treatment — The efficacy of olanzapine tablets for the maintenance treatment of bipolar I disorder in the adolescent population has not been evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.5 Olanzapine Tablets and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder

When using olanzapine tablets and fluoxetine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.

Adults

Oral olanzapine should be administered in combination with fluoxetine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Dosage adjustments, if indicated, can be made according to efficacy and tolerability within dose ranges of oral olanzapine 5 to 12.5 mg and fluoxetine 20 to 50 mg. Antidepressant efficacy was demonstrated with olanzapine tablets and fluoxetine in combination in adult patients with a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg. Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.Children and Adolescents (10 to 17 years of age)

Dosage and Administration information for pediatric patients (10 to 17) is approved for Eli Lilly and Company's olanzapine tablets. However, due to Eli Lilly and Company's marketing exclusivity rights, this drug product is not labeled with that pediatric information.

Safety and efficacy of olanzapine tablets and fluoxetine in combination was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine tablets and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of olanzapine tablets and fluoxetine versus Symbyax. Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability.
Table 1: Approximate Dose Correspondence Between Symbyaxa and the Combination of Olanzapine Tablets and Fluoxetine a Symbyax (olanzapine/fluoxetine hydrochloride) is a fixed-dose combination of olanzapine tablets and fluoxetine. For Symbyax (mg/day) Use in Combination Olanzapine Tablets (mg/day) Fluoxetine (mg/day) 3 mg olanzapine/25 mg fluoxetine 2.5 20 6 mg olanzapine/25 mg fluoxetine 5 20 12 mg olanzapine/25 mg fluoxetine 10+2.5 20 6 mg olanzapine/50 mg fluoxetine 5 40+10 12 mg olanzapine/50 mg fluoxetine 10+2.5 40+10
While there is no body of evidence to answer the question of how long a patient treated with olanzapine tablets and fluoxetine in combination should remain on it, it is generally accepted that bipolar I disorder, including the depressive episodes associated with bipolar I disorder, is a chronic illness requiring chronic treatment. The physician should periodically reexamine the need for continued pharmacotherapy.

Olanzapine tablets monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder.

2.7 Olanzapine Tablets and Fluoxetine in Combination: Dosing in Special Populations

The starting dose of oral olanzapine 2.5 to 5 mg with fluoxetine 20 mg should be used for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine or fluoxetine in combination (female gender, geriatric age, nonsmoking status), or those patients who may be pharmacodynamically sensitive to olanzapine. Dosing modification may be necessary in patients who exhibit a combination of factors that may slow metabolism. When indicated, dose escalation should be performed with caution in these patients. Olanzapine tablets and fluoxetine in combination have not been systematically studied in patients over 65 years of age or in patients under <10 years of age [see Warnings and Precautions (5.12), Drug Interactions (7), and Clinical Pharmacology (12.3)].
Glimepiride

Glimepiride

2.1 Recommended Dosing

Glimepiride tablets should be administered with breakfast or the first main meal of the day.The recommended starting dose of glimepiride tablets is1 mg or 2 mg once daily. Patients at increased risk for hypoglycemia (e.g., the elderly or patients with renal impairment) should be started on 1 mg once daily [see Warnings and Precautions (5.1) and Use in Specific Populations (8.5, 8.6)]. After reaching a daily dose of 2 mg, further dose increases can be made in increments of 1 mg or 2 mg based upon the patient’s glycemic response. Uptitration should not occur more frequently than every 1 to 2 weeks. A conservative titration scheme is recommended for patients at increased risk for hypoglycemia [see Warnings and Precautions (5.1) and Use in Specific Populations (8.5, 8.6)].The maximum recommended dose is 8 mg once daily.Patients being transferred to glimepiride tablets from longer half-life sulfonylureas (e.g., chlorpropamide) may have overlapping drug effect for 1 to 2 weeks and should be appropriately monitored for hypoglycemia.When colesevelam is coadministered with glimepiride, maximum plasma concentration and total exposure to glimepiride is reduced. Therefore, glimepiride tablets should be administered at least 4 hours prior to colesevelam.
Glyburide And Metformin...

Glyburide And Metformin Hydrochloride

General Considerations

Dosage of glyburide and metformin hydrochloride tablets must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glyburide/2000 mg metformin. Glyburide and metformin hydrochloride tablets should be given with meals and should be initiated at a low dose, with gradual dose escalation as described below, in order to avoid hypoglycemia (largely due to glyburide), reduce GI side effects (largely due to metformin), and permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient.With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to glyburide and metformin hydrochloride tablets and to identify the minimum effective dose for the patient. Thereafter, HbA1c should be measured at intervals of approximately 3 months to assess the effectiveness of therapy. The therapeutic goal in all patients with type 2 diabetes is to decrease FPG, PPG, and HbA1c to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA1c (glycosylated hemoglobin), which is a better indicator of long-term glycemic control than FPG alone.No studies have been performed specifically examining the safety and efficacy of switching to glyburide and metformin hydrochloride tablets therapy in patients taking concomitant glyburide (or other sulfonylurea) plus metformin. Changes in glycemic control may occur in such patients, with either hyperglycemia or hypoglycemia possible. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring.

Glyburide and Metformin Hydrochloride Tablets in Patients with Inadequate Glycemic Control on Diet and Exercise

Recommended starting dose: 1.25 mg/250 mg once or twice daily with meals. For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of glyburide and metformin hydrochloride tablets is 1.25 mg/250 mg once a day with a meal. As initial therapy in patients with baseline HbA1c >9% or an FPG >200 mg/dL, a starting dose of glyburide and metformin hydrochloride tablets 1.25 mg/250 mg twice daily with the morning and evening meals may be used. Dosage increases should be made in increments of 1.25 mg/250 mg per day every 2 weeks up to the minimum effective dose necessary to achieve adequate control of blood glucose. In clinical trials of glyburide and metformin hydrochloride tablets as initial therapy, there was no experience with total daily doses >10 mg/2000 mg per day. Glyburide and metformin hydrochloride tablet 5 mg/500 mg should not be used as initial therapy due to an increased risk of hypoglycemia.

Glyburide and Metformin Hydrochloride Tablets Use in Patients with Inadequate Glycemic Control on a Sulfonylurea and/or Metformin

Recommended starting dose: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals.For patients not adequately controlled on either glyburide (or another sulfonylurea) or metformin alone, the recommended starting dose of glyburide and metformin hydrochloride tablets is 2.5 mg/500 mg or 5 mg/500 mg twice daily with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of glyburide and metformin hydrochloride tablets should not exceed the daily doses of glyburide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.For patients previously treated with combination therapy of glyburide (or another sulfonylurea) plus metformin, if switched to glyburide and metformin hydrochloride tablets, the starting dose should not exceed the daily dose of glyburide (or equivalent dose of another sulfonylurea) and metformin already being taken. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of glyburide and metformin hydrochloride tablets should be titrated as described above to achieve adequate control of blood glucose.

Addition of Thiazolidinediones to Glyburide and Metformin Hydrochloride Tablets Therapy

For patients not adequately controlled on glyburide and metformin hydrochloride tablets, a thiazolidinedione can be added to glyburide and metformin hydrochloride tablets therapy. When a thiazolidinedione is added to glyburide and metformin hydrochloride tablets therapy, the current dose of glyburide and metformin hydrochloride tablets can be continued and the thiazolidinedione initiated at its recommended starting dose. For patients needing additional glycemic control, the dose of the thiazolidinedione can be increased based on its recommended titration schedule. The increased glycemic control attainable with glyburide and metformin hydrochloride tablets plus a thiazolidinedione may increase the potential for hypoglycemia at any time of day. In patients who develop hypoglycemia when receiving glyburide and metformin hydrochloride tablets and a thiazolidinedione, consideration should be given to reducing the dose of the glyburide component of glyburide and metformin hydrochloride tablets. As clinically warranted, adjustment of the dosages of the other components of the antidiabetic regimen should also be considered.

Patients Receiving Colesevelam

When colesevelam is coadministered with glyburide, maximum plasma concentration and total exposure to glyburide is reduced. Therefore, glyburide and metformin hydrochloride tablets should be administered at least 4 hours prior to colesevelam.

Specific Patient Populations

Glyburide and metformin hydrochloride tablets are not recommended for use during pregnancy. The initial and maintenance dosing of glyburide and metformin hydrochloride tablets should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment requires a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of glyburide and metformin hydrochloride tablets to avoid the risk of hypoglycemia. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly. (See WARNINGS.)
Naproxen Sodium

Naproxen Sodium

Carefully consider the potential benefits and risks of naproxen sodium tablets and other treatment options before deciding to use naproxen sodium tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).After observing the response to initial therapy with naproxen sodium tablets, the dose and frequency should be adjusted to suit an individual patient's needs. Different dose strengths and formulations (i.e., tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation. Although naproxen tablets, naproxen suspension, naproxen delayed-release tablets and naproxen sodium tablets all circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium.The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients With Moderate to Severe Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) (see WARNINGS: Renal Effects).

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis
Naproxen Sodium Tablets 275 mg (naproxen 250 mg with 25 mg sodium) twice daily 550 mg (naproxen 500 mg with 50 mg sodium) twice daily
During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.In patients who tolerate lower doses well, the dose may be increased to naproxen sodium 1650 mg (equivalent to 1500 mg naproxen) per day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen sodium 1650 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis

The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses (i.e., 5 mg/kg given twice a day). Naproxen tablets are not well suited to this dosage so use of naproxen oral suspension is recommended for this indication.

Management of Pain, Primary Dysmenorrhea, and Acute Tendonitis and Bursitis

The recommended starting dose is 550 mg of naproxen sodium followed by 550 mg every 12 hours or 275 mg every 6 to 8 hours as required. The initial total daily dose should not exceed 1375 mg of naproxen sodium. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen is more rapidly absorbed, naproxen sodium tablets are recommended for the management of acute painful conditions when prompt onset of pain relief is desired.

Acute Gout

Naproxen sodium tablets may be used at a starting dose of 825 mg followed by 275 mg every 8 hours.
Naproxen

Naproxen

Carefully consider the potential benefits and risks of naproxen tablets and other treatment options before deciding to use naproxen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).After observing the response to initial therapy with naproxen tablets, the dose and frequency should be adjusted to suit an individual patient's needs.Different dose strengths and formulations (i.e., tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation. Although naproxen tablets, naproxen suspension, naproxen delayed-release tablets and naproxen sodium tablets all circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 1 hour in patients taking naproxen.The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients With Moderate to Severe Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) (see WARNINGS: Renal Effects).

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis
Naproxen Tablets 250 mg or 375 mg or 500 mg twice daily twice daily twice daily
During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis

The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses (i.e., 5 mg/kg given twice a day). Naproxen tablets are not well suited to this dosage so use of naproxen oral suspension is recommended for this indication.

Management of Pain, Primary Dysmenorrhea, and Acute Tendonitis and Bursitis

Because the sodium salt of naproxen is more rapidly absorbed, naproxen sodium is recommended for the management of acute painful conditions when prompt onset of pain relief is desired. Naproxen tablets may also be used. The recommended starting dose of naproxen tablets is 500 mg, followed by 500 mg every 12 hours or 250 mg every 6 to 8 hours as required. The initial total daily dose should not exceed 1250 mg of naproxen. Thereafter, the total daily dose should not exceed 1000 mg of naproxen.

Acute Gout

The recommended starting dose is 750 mg of naproxen tablets followed by 250 mg every 8 hours until the attack has subsided.
Terbinafine

Terbinafine

Fingernail onychomycosis: One 250 mg tablet once daily for 6 weeks.Toenail onychomycosis: One 250 mg tablet once daily for 12 weeks.The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail.
Fosinopril Sodium And H...

Fosinopril Sodium And Hydrochlorothiazide

Fosinopril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide is effective in doses of 12.5 to 50 mg per day. In clinical trials of fosinopril/hydrochlorothiazide combination therapy using fosinopril doses of 2.5 to 40 mg and hydrochlorothiazide doses at 5 to 37.5 mg, the antihypertensive effects increased with increasing dose of either component.

The hazards (see WARNINGS.) of fosinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of fosinopril and hydrochlorothiazide will be associated with both sets of dose-independent hazards. To minimize dose-independent hazards, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration by Clinical Effect

A patient whose blood pressure is not adequately controlled with fosinopril or hydrochlorothiazide monotherapy may be switched to combination therapy with fosinopril sodium and hydrochlorothiazide tablets. Dosage must be guided by clinical response; controlled clinical trials showed that the addition of 12.5 mg of hydrochlorothiazide to 10 to 20 mg of fosinopril will typically be associated with additional reduction in seated diastolic blood pressure at 24 hours after dosing. On average, the effect of the combination of 10 mg of fosinopril with 12.5 mg of hydrochlorothiazide was similar to the effect seen with monotherapy using either 40 mg of fosinopril or 37.5 mg of hydrochlorothiazide.

Use in Renal Impairment

In patients with severe renal impairment (creatinine clearance is <30 mL/min/1.73 m2, serum creatine roughly ≥3 mg/dL or 265 µmol/L), loop diuretics are preferred to thiazides, so fosinopril sodium and hydrochlorothiazide tablets are not recommended. In patients with lesser degrees of renal impairment, fosinopril sodium and hydrochlorothiazide tablets may be used with no change in dosage.
Fosinopril Sodium

Fosinopril Sodium

Hypertension

Adults

The recommended initial dose of fosinopril sodium tablets is 10 mg once a day, both as monotherapy and when the drug is added to a diuretic. Dosage should then be adjusted according to blood pressure response at peak (2 to 6 hours) and trough (about 24 hours after dosing) blood levels. The usual dosage range needed to maintain a response at trough is 20 to 40 mg but some patients appear to have a further response to 80 mg. In some patients treated with once daily dosing, the antihypertensive effect may diminish toward the end of the dosing interval. If trough response is inadequate, dividing the daily dose should be considered. If blood pressure is not adequately controlled with fosinopril sodium tablets alone, a diuretic may be added.Concomitant administration of fosinopril sodium tablets with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium (see PRECAUTIONS).In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of fosinopril sodium tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with fosinopril sodium tablets (see WARNINGS). Then, if blood pressure is not controlled with fosinopril sodium tablets alone, diuretic therapy should be resumed. If diuretic therapy cannot be discontinued, an initial dose of 10 mg of fosinopril sodium tablets should be used with careful medical supervision for several hours and until blood pressure has stabilized. (See WARNINGS and PRECAUTIONS: Information for Patients and Drug Interactions.)Since concomitant administration of fosinopril sodium tablets with potassium supplements, or potassium-containing salt substitutes or potassium-sparing diuretics may lead to increases in serum potassium, they should be used with caution (see PRECAUTIONS).

Pediatrics

In children, doses of fosinopril sodium tablets between 0.1 and 0.6 mg/kg have been studied and shown to reduce blood pressure to a similar extent (see CLINICAL PHARMACOLOGY: Pharmacodynamics and Clinical Effects). Based on this, the recommended dose of fosinopril sodium tablets in children weighing more than 50 kg is 5 to 10 mg once per day as monotherapy. An appropriate dosage strength is not available for children weighing less than 50 kg.

Heart Failure

Digitalis is not required for fosinopril sodium tablets to manifest improvements in exercise tolerance and symptoms. Most placebo-controlled clinical trial experience has been with both digitalis and diuretics present as background therapy.The usual starting dose of fosinopril sodium tablets should be 10 mg once daily. Following the initial dose of fosinopril sodium tablets, the patient should be observed under medical supervision for at least 2 hours for the presence of hypotension or orthostasis, and if present, until blood pressure stabilizes. An initial dose of 5 mg is preferred in heart failure patients with moderate to severe renal failure or those who have been vigorously diuresed.Dosage should be increased, over a several week period, to a dose that is maximal and tolerated but not exceeding 40 mg once daily. The usual effective dosage range is 20 to 40 mg once daily.The appearance of hypotension, orthostasis, or azotemia early in dose titration should not preclude further careful dose titration. Consideration should be given to reducing the dose of concomitant diuretic.

For Hypertensive or Heart Failure Patients With Renal Impairment

In patients with impaired renal function, the total body clearance of fosinoprilat is approximately 50% slower than in patients with normal renal function. Since hepatobiliary elimination partially compensates for diminished renal elimination, the total body clearance of fosinoprilat does not differ appreciably with any degree of renal insufficiency (creatinine clearances <80 mL/min/1.73 m2), including end-stage renal failure (creatinine clearance <10 mL/min/1.73 m2). This relative constancy of body clearance of active fosinoprilat, resulting from the dual route of elimination, permits use of the usual dose in patients with any degree of renal impairment. (See WARNINGS: Anaphylactoid reactions during membrane exposure

and PRECAUTIONS: Hemodialysis.)
Minocycline Hydrochlori...

Minocycline Hydrochloride

The recommended dosage of minocycline hydrochloride extended-release tablets is approximately 1 mg/kg once daily for 12 weeks. Higher doses have not shown to be of additional benefit in the treatment of inflammatory lesions of acne, and may be associated with more acute vestibular side effects.The following table shows tablet strength and body weight to achieve approximately 1 mg/kg.
Table 1: Dosing Table for Minocycline Hydrochloride Extended-Release Tablets Patient’s Weight (lbs.) Patient’sWeight (kg) Tablet Strength (mg) Actual mg/kg Dose 99 to 109 45 to 49 45 1 to 0.92 110 to 131 50 to 59 55 1.1 to 0.93 132 to 157 60 to 71 65 1.08 to 0.92 158 to 186 72 to 84 80 1.11 to 0.95 187 to 212 85 to 96 90 1.06 to 0.94 213 to 243 97 to 110 105 1.08 to 0.95 244 to 276 111 to 125 115 1.04 to 0.92 277 to 300 126 to 136 135 1.07 to 0.99
Minocycline hydrochloride extended-release tablets may be taken with or without food [see CLINICAL PHARMACOLOGY (12.3)]. Ingestion of food along with minocycline hydrochloride extended-release tablets may help reduce the risk of esophageal irritation and ulceration.In patients with renal impairment, the total dosage should be decreased by either reducing the recommended individual doses and/or by extending the time intervals between doses [see WARNINGS AND PRECAUTIONS (5.4)].
Quetiapine Fumarate

Quetiapine Fumarate

2.1 Important Administration Instructions

Quetiapine fumarate tablets can be taken with or without food.

2.2 Recommended Dosing

The recommended initial dose, titration, dose range and maximum quetiapine fumarate tablets dose for each approved indication is displayed in Table 1. After initial dosing, adjustments can be made upwards or downwards, if necessary, depending upon the clinical response and tolerability of the patient [see Clinical Studies (14.1 and 14.2)].
Table 1: Recommended Dosing for quetiapine fumarate tablets 1. N/A Not applicable Indication Initial Dose and Titration Recommended Dose Maximum Dose Schizophrenia-Adults Day 1: 25 mg twice daily. Increase in increments of 25 mg to 50 mg divided two or three times on Days 2 and 3 to range of 300 to 400 mg by Day 4.Further adjustments can be made in increments of 25 to 50 mg twice a day, in intervals of not less than 2 days. 150 to 750 mg/day 750 mg/day Schizophrenia-Adolescents (13 to 17years) Day 1: 25 mg twice daily.Day 2: Twice daily dosing totaling 100 mg.Day 3: Twice daily dosing totaling 200 mg.Day 4: Twice daily dosing totaling 300 mg.Day 5: Twice daily dosing totaling 400 mg.Further adjustments should bein increments no greater than100 mg/day within therecommended dose range of400 to 800 mg/day.Based on response andtolerability, may beadministered three times daily. 400 to 800 mg/day 800 mg/day Schizophrenia-Maintenance N/A1 400 to 800 mg/day 800 mg/day Bipolar Mania- AdultsMonotherapy or as anadjunct to lithium ordivalproex Day 1: Twice daily dosing totaling 100 mg.Day 2: Twice daily dosing totaling 200 mg.Day 3: Twice daily dosing totaling 300 mg.Day 4: Twice daily dosing totaling 400 mg.Further dosage adjustments up to 800 mg/day by Day 6 should be in increments of no greater than 200 mg/day. 400 to 800 mg/day 800 mg/day Bipolar Mania- Children and Adolescents (10 to 17years), Monotherapy Day 1: 25 mg twice daily.Day 2: Twice daily dosing totaling 100 mg.Day 3: Twice daily dosing totaling 200 mg.Day 4: Twice daily dosing totaling 300 mg.Day 5: Twice daily dosing totaling 400 mg.Further adjustments should be in increments no greater than 100 mg/day within the recommended dose range of 400 to 600 mg/day.Based on response and tolerability, may be administered three times daily. 400 to 600 mg/day 600 mg/day Bipolar Depression-Adults Administer once daily at bedtime. Day 1: 50 mgDay 2: 100 mgDay 3: 200 mgDay 4: 300 mg 300 mg/day 300 mg/day Bipolar I DisorderMaintenance Therapy-Adults Administer twice daily totaling 400 to 800 mg/day as adjunct to lithium or divalproex. Generally, in the maintenance phase, patients continued on the same dose on which they were stabilized. 400 to 800 mg/day 800 mg/day
Maintenance Treatment for Schizophrenia and Bipolar I Disorder

Maintenance Treatment-Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2)].

2.3 Dose Modifications in Elderly Patients

Consideration should be given to a slower rate of dose titration and a lower target dose in the elderly and in patients who are debilitated or who have a predisposition to hypotensive reactions [see Clinical Pharmacology (12.3)]. When indicated, dose escalation should be performed with caution in these patients.Elderly patients should be started on quetiapine fumarate tablets 50 mg/day and the dose can be increased in increments of 50 mg/day depending on the clinical response and tolerability of the individual patient.

2.4 Dose Modifications in Hepatically Impaired Patients

Patients with hepatic impairment should be started on 25 mg/day. The dose should be increased daily in increments of 25 mg/day to 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.

2.5 Dose Modifications when used with CYP3A4 Inhibitors

Quetiapine fumarate tablets dose should be reduced to one sixth of original dose when co-medicated with a potent CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). When the CYP3A4 inhibitor is discontinued, the dose of quetiapine fumarate tablets should be increased by 6 fold [see Clinical Pharmacology (12.3) and Drug Interactions (7.1)].

2.6 Dose Modifications when used with CYP3A4 Inducers

Quetiapine fumarate tablets dose should be increased up to 5 fold of the original dose when used in combination with a chronic treatment (e.g., greater than 7 to 14 days) of a potent CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.). The dose should be titrated based on the clinical response and tolerability of the individual patient. When the CYP3A4 inducer is discontinued, the dose of quetiapine fumarate tablets should be reduced to the original level within 7 to 14 days [see Clinical Pharmacology (12.3) and Drug Interactions (7.1)].

2.7 Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address re-initiation of treatment, it is recommended that when restarting therapy of patients who have been off quetiapine fumarate tablets for more than one week, the initial dosing schedule should be followed. When restarting patients who have been off quetiapine fumarate tablets for less than one week, gradual dose escalation may not be required and the maintenance dose may be reinitiated.

2.8 Switching from Antipsychotics

There are no systematically collected data to specifically address switching patients with schizophrenia from antipsychotics to quetiapine fumarate tablets, or concerning concomitant administration with antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. When switching patients with schizophrenia from depot antipsychotics, if medically appropriate, initiate quetiapine fumarate tablets therapy in place of the next scheduled injection. The need for continuing existing EPS medication should be re-evaluated periodically.
Trandolapril

Trandolapril

HypertensionThe recommended initial dosage of trandolapril tablets for patients not receiving a diuretic is 1 mg once daily in non-Black patients and 2 mg in Black patients. Dosage should be adjusted according to the blood pressure response. Generally, dosage adjustments should be made at intervals of at least 1 week. Most patients have required dosages of 2 to 4 mg once daily. There is little clinical experience with doses above 8 mg. Patients inadequately treated with once-daily dosing at 4 mg may be treated with twice-daily dosing. If blood pressure is not adequately controlled with trandolapril tablets monotherapy, a diuretic may be added.In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of trandolapril tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with trandolapril tablets. (See WARNINGS.) Then, if blood pressure is not controlled with trandolapril tablets alone, diuretic therapy should be resumed. If the diuretic cannot be discontinued, an initial dose of 0.5 mg trandolapril tablets should be used with careful medical supervision for several hours until blood pressure has stabilized. The dosage should subsequently be titrated (as described above) to the optimal response. (See WARNINGS, PRECAUTIONS and Drug Interactions.) Concomitant administration of trandolapril tablets with potassium supplements, potassium salt substitutes, or potassium sparing diuretics can lead to increases of serum potassium. (See PRECAUTIONS.) Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction The recommended starting dose is 1 mg, once daily. Following the initial dose, all patients should be titrated (as tolerated) toward a target dose of 4 mg, once daily. If a 4 mg dose is not tolerated, patients can continue therapy with the greatest tolerated dose.

Dosage Adjustment in Renal Impairment or Hepatic Cirrhosis

For patients with a creatinine clearance <30 mL/min. or with hepatic cirrhosis, the recommended starting dose, based on clinical and pharmacokinetic data, is 0.5 mg daily. Patients should subsequently have their dosage titrated (as described above) to the optimal response.
Sulfamethoxazole And Tr...

Sulfamethoxazole And Trimethoprim

Sulfamethoxazole and trimethoprim tablets are contraindicated in pediatric patients less than 2 months of age.

Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children

Adults

The usual adult dosage in the treatment of urinary tract infections is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet or 2 sulfamethoxazole and trimethoprim tablets every 12 hours for 10 to 14 days. An identical daily dosage is used for 5 days in the treatment of shigellosis.

Children

The recommended dose for children with urinary tract infections or acute otitis media is 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. The following table is a guideline for the attainment of this dosage:Children 2 months of age or older:
Weight Dose–every 12 hours lb kg Tablets 22446688 10203040 –11½2 or 1 DS tablet
For Patients with Impaired Renal Function

When renal function is impaired, a reduced dosage should be employed using the following table:
Creatinine Clearance (mL/min) Recommended Dosage Regimen Above 3015–30Below 15 Usual standard regimen½ the usual regimenUse not recommended
Acute Exacerbations of Chronic Bronchitis in Adults

The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet or 2 sulfamethoxazole and trimethoprim tablets every 12 hours for 14 days. Pneumocystis Jiroveci Pneumonia Treatment Adults and Children The recommended dosage for treatment of patients with documented Pneumocystis jiroveci pneumonia is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days.11 The following table is a guideline for the upper limit of this dosage:
Weight Dose–every 6 hours lb kg Tablets 1835537088106141176 816243240486480 –11½2 or 1 DS tablet2½3 or 1½ DS tablets4 or 2 DS tablets5 or 2½ DS tablets
For the lower limit dose (75 mg/kg sulfamethoxazole and 15 mg/kg trimethoprim per 24 hours) administer 75% of the dose in the above table.Prophylaxis Adults The recommended dosage for prophylaxis in adults is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet daily.12 ChildrenFor children, the recommended dose is 750 mg/m2/day sulfamethoxazole with 150 mg/m2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week. The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim.13 The following table is a guideline for the attainment of this dosage in children:
Body Surface Area Dose–every 12 hours (m2) Tablets 0.260.531.06 –½1
Traveler's Diarrhea in Adults

For the treatment of traveler’s diarrhea, the usual adult dosage is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet or 2 sulfamethoxazole and trimethoprim tablets every 12 hours for 5 days.
Atenolol

Atenolol

Hypertension The initial dose of atenolol is 50 mg given as one tablet a day either alone or added to diuretic therapy. The full effect of this dose will usually be seen within one to two weeks. If an optimal response is not achieved, the dosage should be increased to atenolol 100 mg given as one tablet a day. Increasing the dosage beyond 100 mg a day is unlikely to produce any further benefit.Atenolol may be used alone or concomitantly with other antihypertensive agents including thiazide-type diuretics, hydralazine, prazosin, and alpha-methyldopa. Angina Pectoris The initial dose of atenolol is 50 mg given as one tablet a day. If an optimal response is not achieved within one week, the dosage should be increased to atenolol 100 mg given as one tablet a day. Some patients may require a dosage of 200 mg once a day for optimal effect.Twenty-four hour control with once daily dosing is achieved by giving doses larger than necessary to achieve an immediate maximum effect. The maximum early effect on exercise tolerance occurs with doses of 50 to 100 mg, but at these doses the effect at 24 hours is attenuated, averaging about 50% to 75% of that observed with once a day oral doses of 200 mg.Acute Myocardial Infarction In patients with definite or suspected acute myocardial infarction, treatment with atenolol I.V. injection should be initiated as soon as possible after the patient's arrival in the hospital and after eligibility is established. Such treatment should be initiated in a coronary care or similar unit immediately after the patient's hemodynamic condition has stabilized. Treatment should begin with the intravenous administration of 5 mg atenolol over 5 minutes followed by another 5 mg intravenous injection 10 minutes later. Atenolol I.V. injection should be administered under carefully controlled conditions including monitoring of blood pressure, heart rate, and electrocardiogram. Dilutions of atenolol I.V. injection in dextrose injection USP, sodium chloride injection USP, or sodium chloride and dextrose injection may be used. These admixtures are stable for 48 hours if they are not used immediately.In patients who tolerate the full intravenous dose (10 mg), atenolol tablets 50 mg should be initiated 10 minutes after the last intravenous dose followed by another 50 mg oral dose 12 hours later. Thereafter, atenolol can be given orally either 100 mg once daily or 50 mg twice a day for a further 6 to 9 days or until discharge from the hospital. If bradycardia or hypotension requiring treatment or any other untoward effects occur, atenolol should be discontinued. (See full prescribing information prior to initiating therapy with atenolol tablets.)Data from other beta-blocker trials suggest that if there is any question concerning the use of IV beta-blocker or clinical estimate that there is a contraindication, the IV beta-blocker may be eliminated and patients fulfilling the safety criteria may be given atenolol tablets 50 mg twice daily or 100 mg once a day for at least seven days (if the IV dosing is excluded).Although the demonstration of efficacy of atenolol is based entirely on data from the first seven postinfarction days, data from other beta-blocker trials suggest that treatment with beta-blockers that are effective in the postinfarction setting may be continued for one to three years if there are no contraindications.Atenolol is an additional treatment to standard coronary care unit therapy. Elderly Patients or Patients with Renal Impairment Atenolol is excreted by the kidneys; consequently dosage should be adjusted in cases of severe impairment of renal function. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function. Atenolol excretion would be expected to decrease with advancing age.No significant accumulation of atenolol occurs until creatinine clearance falls below 35 mL/min/1.73 m2. Accumulation of atenolol and prolongation of its half-life were studied in subjects with creatinine clearance between 5 and 105 mL/min. Peak plasma levels were significantly increased in subjects with creatinine clearances below 30 mL/min.The following maximum oral dosages are recommended for elderly, renally-impaired patients and for patients with renal impairment due to other causes:
Creatinine Clearance (mL/min/1.73 m2) Atenolol Elimination Half-Life(h) Maximum Dosage 15-35 16-27 50 mg daily <15 >27 25 mg daily
Some renally-impaired or elderly patients being treated for hypertension may require a lower starting dose of atenolol: 25 mg given as one tablet a day. If this 25 mg dose is used, assessment of efficacy must be made carefully. This should include measurement of blood pressure just prior to the next dose ("trough" blood pressure) to ensure that the treatment effect is present for a full 24 hours.Although a similar dosage reduction may be considered for elderly and/or renally-impaired patients being treated for indications other than hypertension, data are not available for these patient populations.Patients on hemodialysis should be given 25 mg or 50 mg after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.Cessation of Therapy in Patients with Angina Pectoris If withdrawal of atenolol therapy is planned, it should be achieved gradually and patients should be carefully observed and advised to limit physical activity to a minimum.
Alprazolam

Alprazolam

Alprazolam extended-release tablets may be administered once daily, preferably in the morning. The tablets should be taken intact; they should not be chewed, crushed, or broken.The suggested total daily dose ranges between 3 to 6 mg/day. Dosage should be individualized for maximum beneficial effect. While the suggested total daily dosages given will meet the needs of most patients, there will be some patients who require doses greater than 6 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects. Dosing in Special Populations In elderly patients, in patients with advanced liver disease, or in patients with debilitating disease, the usual starting dose of alprazolam extended-release tablets is 0.5 mg once daily. This may be gradually increased if needed and tolerated (see Dose Titration). The elderly may be especially sensitive to the effects of benzodiazepines.

Dose Titration

Treatment with alprazolam extended-release tablets may be initiated with a dose of 0.5 mg to 1 mg once daily. Depending on the response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg/day. Slower titration to the dose levels may be advisable to allow full expression of the pharmacodynamic effect of alprazolam extended-release tablets.Generally, therapy should be initiated at a low dose to minimize the risk of adverse responses in patients especially sensitive to the drug. Dose should be advanced until an acceptable therapeutic response (i.e., a substantial reduction in or total elimination of panic attacks) is achieved, intolerance occurs, or the maximum recommended dose is attained. Dose Maintenance In controlled trials conducted to establish the efficacy of alprazolam extended-release tablets in panic disorder, doses in the range of 1 to 10 mg/day were used. Most patients showed efficacy in the dose range of 3 to 6 mg/day. Occasional patients required as much as 10 mg/day to achieve a successful response.The necessary duration of treatment for panic disorder patients responding to alprazolam extended-release tablets is unknown. However, periodic reassessment is advised. After a period of extended freedom from attacks, a carefully supervised tapered discontinuation may be attempted, but there is evidence that this may often be difficult to accomplish without recurrence of symptoms and/or the manifestation of withdrawal phenomena. Dose Reduction Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided (see WARNINGS, PRECAUTIONS, and DRUG ABUSE AND DEPENDENCE).In all patients, dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage. Although there are no systematically collected data to support a specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.In any case, reduction of dose must be undertaken under close supervision and must be gradual. If significant withdrawal symptoms develop, the previous dosing schedule should be reinstituted and, only after stabilization, should a less rapid schedule of discontinuation be attempted. In a controlled postmarketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. It is suggested that the dose be reduced by no more than 0.5 mg every three days, with the understanding that some patients may benefit from an even more gradual discontinuation. Some patients may prove resistant to all discontinuation regimens. Switch from Alprazolam (Immediate-Release) Tablets to Alprazolam Extended-Release Tablets Patients who are currently being treated with divided doses of alprazolam (immediate-release) tablets, for example 3 to 4 times a day, may be switched to alprazolam extended-release tablets at the same total daily dose taken once daily. If the therapeutic response after switching is inadequate, the dosage may be titrated as outlined above.
Cyclobenzaprine Hydroch...

Cyclobenzaprine Hydrochloride

For most patients, the recommended dose of cyclobenzaprine hydrochloride tablets are 5 mg three times a day. Based on individual patient response, the dose may be increased to 10 mg three times a day. Use of cyclobenzaprine hydrochloride tablets for periods longer than two or three weeks are not recommended. (see INDICATIONS AND USAGE).Less frequent dosing should be considered for hepatically impaired or elderly patients (see PRECAUTIONS, Impaired Hepatic Function, and Use in the Elderly).
Lisinopril And Hydrochl...

Lisinopril And Hydrochlorothiazide

Lisinopril monotherapy is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide monotherapy is effective in doses of 12.5 to 50 mg per day. In clinical trials of lisinopril and hydrochlorothiazide tablets combination therapy using lisinopril doses of 10 to 80 mg and hydrochlorothiazide doses of 6.25 to 50 mg, the antihypertensive response rates generally increased with increasing dose of either component.The side effects (see WARNINGS) of lisinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of lisinopril and hydrochlorothiazide may be associated with either or both dose-independent or dose-dependent side effects, but addition of lisinopril in clinical trials blunted the hypokalemia normally seen with diuretics.To minimize dose-dependent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration Guided by Clinical Effect

A patient whose blood pressure is not adequately controlled with either lisinopril or hydrochlorothiazide monotherapy may be switched to lisinopril and hydrochlorothiazide tablets 10 mg/12.5 mg or lisinopril and hydrochlorothiazide tablets 20 mg/12.5 mg, depending on current monotherapy dose. Further increases of either or both components should depend on clinical response with blood pressure measured at the interdosing interval to ensure that there is an adequate antihypertensive effect at that time. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. After addition of the diuretic it may be possible to reduce the dose of lisinopril. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen may achieve similar or greater blood-pressure control without electrolyte disturbance if they are switched to lisinopril and hydrochlorothiazide tablets 10 mg/12.5 mg.In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may occur following the initial dose of lisinopril. The diuretic should, if possible, be discontinued for two to three days before beginning therapy with lisinopril to reduce the likelihood of hypotension. (See WARNINGS.) If the patient’s blood pressure is not controlled with lisinopril alone, diuretic therapy may be resumed.If the diuretic cannot be discontinued, an initial dose of 5 mg of lisinopril should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS and PRECAUTIONS, Drug Interactions).Concomitant administration of lisinopril and hydrochlorothiazide tablets with potassium supplements, potassium salt substitutes or potassium-sparing diuretics may lead to increases of serum potassium (see PRECAUTIONS).

Replacement Therapy

The combination may be substituted for the titrated individual components.

Use in Renal Impairment

Regimens of therapy with lisinopril and hydrochlorothiazide tablets need not take account of renal function as long as the patient’s creatinine clearance is >30 mL/min/1.7 m2 (serum creatinine roughly ≤3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so lisinopril and hydrochlorothiazide tablets are not recommended (see WARNINGS, Anaphylactoid Reactions During Membrane Exposure).
Sumatriptan

Sumatriptan

2.1 Dosing Information

The recommended dose of sumatriptan tablets is 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25 mg dose, but doses of 100 mg may not provide a greater effect than the 50 mg dose. Higher doses may have a greater risk of adverse reactions [see Clinical Studies (14)].If the migraine has not resolved by 2 hours after taking sumatriptan tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24-hour period. Use after Sumatriptan Injection: If the migraine returns following an initial treatment with sumatriptan Injection, additional single sumatriptan tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses.The safety of treating an average of more than 4 headaches in a 30-day period has not been established.

2.2 Dosing in Patients With Hepatic Impairment

If treatment is deemed advisable in the presence of mild to moderate hepatic impairment, the maximum single dose should not exceed 50 mg [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Pioglitazone Hydrochlor...

Pioglitazone Hydrochloride

2.1 Recommendations for All Patients

Pioglitazone tablets should be taken once daily and can be taken without regard to meals.The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily.The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily.The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c.After initiation of pioglitazone tablets or with dose increase, monitor patients carefully for adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure [see Boxed Warning and Warnings and Precautions (5.5)].Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone tablets. Routine periodic monitoring of liver tests during treatment with pioglitazone tablets are not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of pioglitazone tablets or who are found to have abnormal liver tests while taking pioglitazone tablets should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

2.2 Concomitant Use with an Insulin Secretagogue or Insulin

If hypoglycemia occurs in a patient coadministered pioglitazone tablets and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced.If hypoglycemia occurs in a patient coadministered pioglitazone tablets and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response.

2.3 Concomitant Use with Strong CYP2C8 Inhibitors

Coadministration of pioglitazone tablets and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of pioglitazone tablets are 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Montelukast Sodium

Montelukast Sodium

2.1 Asthma

Montelukast sodium should be taken once daily in the evening. The following doses are recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.For pediatric patients 6 to 14 years of age: one 5 mg chewable tablet.For pediatric patients 2 to 5 years of age: one 4 mg chewable tablet.Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established.There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing. The pharmacokinetics of montelukast are similar whether dosed in the morning or evening. Efficacy has been demonstrated for asthma when montelukast was administered in the evening without regard to time of food ingestion.

2.2 Exercise-lnduced Bronchoconstriction (EIB)

For prevention of EIB, a single dose of montelukast should be taken at least 2 hours before exercise. The following doses are recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.For pediatric patients 6 to 14 years of age: one 5 mg chewable tablet.An additional dose of montelukast sodium should not be taken within 24 hours of a previous dose. Patients already taking montelukast sodium daily for another indication (including chronic asthma) should not take an additional dose to prevent EIB. All patients should have available for rescue a short-acting β-agonist. Safety and efficacy in patients younger than 6 years of age have not been established. Daily administration of montelukast sodium for the chronic treatment of asthma has not been established to prevent acute episodes of EIB.

2.3 Allergic Rhinitis

For allergic rhinitis, montelukast sodium should be taken once daily. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion. The time of administration may be individualized to suit patient needs.The following doses for the treatment of symptoms of seasonal allergic rhinitis are recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.For pediatric patients 6 to 14 years of age: one 5 mg chewable tablet.For pediatric patients 2 to 5 years of age: one 4 mg chewable tablet.Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.The following doses for the treatment of symptoms of perennial allergic rhinitis are recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.For pediatric patients 6 to 14 years of age: one 5 mg chewable tablet.For pediatric patients 2 to 5 years of age: one 4 mg chewable tablet.Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic rhinitis have not been established.

2.4 Asthma and Allergic Rhinitis

Patients with both asthma and allergic rhinitis should take only one montelukast sodium dose daily in the evening.
Pantoprazole Sodium

Pantoprazole Sodium

2.1 Recommended Dosing Schedule

Pantoprazole sodium is supplied as delayed-release tablets. The recommended dosages are outlined in Table 1.
Table 1: Recommended Dosing Schedule for Pantoprazole Sodium Delayed-Release Tablets * For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium delayed-release tablets may be considered.** Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered. *** Controlled studies did not extend beyond 12 months Indication Dose Frequency Short-Term Treatment of Erosive Esophagitis Associated With GERD Adults 40 mg Once daily for up to 8 weeks* Children (5 years and older) ≥ 15 kg to < 40 kg 20 mg Once daily for up to 8 weeks ≥ 40 kg 40 mg Maintenance of Healing of Erosive Esophagitis Adults 40 mg Once daily*** Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Adults 40 mg Twice daily**
2.2 Administration Instructions

Directions for method of administration of pantoprazole sodium delayed-release tablets are presented in Table 2.
Table 2: Administration Instructions * Patients should be cautioned that pantoprazole sodium delayed-release tablets should not be split, chewed, or crushed. Formulation Route Instructions* Delayed-Release Tablets Oral Swallowed whole, with or without food
Pantoprazole sodium delayed-release tablets should be swallowed whole, with or without food in the stomach. If patients are unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of pantoprazole sodium delayed-release tablets.
Sedalia

Sedalia

2.1 Adult Patients

The recommended dose for nevirapine oral suspension is 200 mg daily for the first 14 days, followed by 200 mg twice daily, in combination with other antiretroviral agents. The lead-in period has been observed to decrease the incidence of rash. For concomitantly administered antiretroviral therapy, the manufacturer’s recommended dosage and monitoring should be followed.

2.2 Pediatric Patients

The recommended oral dose for pediatric patients 15 days and older is 150 mg/m2 once daily for 14 days followed by 150 mg/m2 twice daily thereafter. The total daily dose should not exceed 400 mg for any patient.
Table 1 Calculation of the Volume of Nevirapine Oral Suspension (50 mg per 5 mL) Required for Pediatric Dosing Based on Body Surface and a Dose of 150 mg/m2 BSA range (m2) Volume (mL) 0.06 – 0.12 1.25 0.12 – 0.25 2.5 0.25 – 0.42 5 0.42 – 0.58 7.5 0.58 – 0.75 10 0.75 – 0.92 12.5 0.92 – 1.08 15 1.08 – 1.25 17.5 1.25+ 20
Nevirapine suspension should be shaken gently prior to administration. It is important to administer the entire measured dose of suspension by using an oral dosing syringe or dosing cup. An oral dosing syringe is recommended, particularly for volumes of 5 mL or less. If a dosing cup is used, it should be thoroughly rinsed with water and the rinse should also be administered to the patient.

2.3 Monitoring of Patients

Intensive clinical and laboratory monitoring, including liver enzyme tests, is essential at baseline and during the first 18 weeks of treatment with nevirapine oral suspension. The optimal frequency of monitoring during this period has not been established. Some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, would include monitoring of liver enzyme tests at baseline, prior to dose escalation, and at two weeks post-dose escalation. After the initial 18-week period, frequent clinical and laboratory monitoring should continue throughout nevirapine oral suspension treatment [see Warnings and Precautions (5)]. In some cases, hepatic injury has progressed despite discontinuation of treatment.

2.4 Dosage Adjustment

Patients with Rash Discontinue nevirapine oral suspension if a patient experiences severe rash or any rash accompanied by constitutional findings [see Boxed Warning and Warnings and Precautions (5.2)].

Do not increase nevirapine oral suspension dose if a patient experiences mild to moderate rash without constitutional symptoms during the 14-day lead-in period of 200 mg/day (150 mg/m2/day in pediatric patients) until the rash has resolved [see Warnings and Precautions (5.2)]. The total duration of the once daily lead-in dosing period should not exceed 28 days at which point an alternative regimen should be sought. Patients with Hepatic Events If a clinical (symptomatic) hepatic event occurs, permanently discontinue nevirapine oral suspension. Do not restart nevirapine oral suspension after recovery [see Warnings and Precautions (5.1)].Patients with Dose Interruption For patients who interrupt nevirapine oral suspension dosing for more than 7 days, restart the recommended dosing, 200 mg daily (150 mg/m2/day in pediatric patients) for the first 14 days (lead-in) followed by 200 mg twice daily (150 mg/m2 twice daily for pediatric patients).Patients with Renal Impairment Patients with CrCL greater than or equal to 20 mL per min do not require an adjustment in nevirapine oral suspension dosing. The pharmacokinetics of nevirapine have not been evaluated in patients with CrCL less than 20 mL per min. An additional 200 mg dose of nevirapine oral suspension following each dialysis treatment is indicated in patients requiring dialysis. Nevirapine metabolites may accumulate in patients receiving dialysis; however, the clinical significance of this accumulation is not known [see Clinical Pharmacology (12.3)].
Clopidogrel

Clopidogrel

2.1 Acute Coronary Syndrome

Clopidogrel tablets can be administered with or without food [see Clinical Pharmacology (12.3)].
For patients with non-ST-elevation ACS (UA/NSTEMI), initiate clopidogrel tablets with a single 300 mg oral loading dose and then continue at 75 mg once daily. Initiate aspirin (75 to 325 mg once daily) and continue in combination with clopidogrel tablets [see Clinical Studies (14.1)]. For patients with STEMI, the recommended dose of clopidogrel tablet is 75 mg once daily orally, administered in combination with aspirin (75 to 325 mg once daily), with or without thrombolytics. Clopidogrel tablets may be initiated with or without a loading dose [see Clinical Studies (14.1)].
2.2 Recent MI, Recent Stroke, or Established Peripheral Arterial Disease

The recommended daily dose of clopidogrel tablet is 75 mg once daily orally, with or without food [see Clinical Pharmacology (12.3)].

2.3 CYP2C19 Poor Metabolizers

CYP2C19 poor metabolizer status is associated with diminished antiplatelet response to clopidogrel. Although a higher dose regimen in poor metabolizers increases antiplatelet response [see Clinical Pharmacology (12.5)], an appropriate dose regimen for this patient population has not been established.

2.4 Use with Proton Pump Inhibitors (PPI)

Avoid using omeprazole or esomeprazole with clopidogrel tablets. Omeprazole and esomeprazole significantly reduce the antiplatelet activity of clopidogrel tablets. When concomitant administration of a PPI is required, consider using another acid-reducing agent with minimal or no CYP2C19 inhibitory effect on the formation of clopidogrel active metabolite [see Warnings and Precautions (5.1), Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Repaglinide

Repaglinide

There is no fixed dosage regimen for the management of type 2 diabetes with repaglinide tablets.The patient’s blood glucose should be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels are of value in monitoring the patient’s longer term response to therapy.Short-term administration of repaglinide tablets may be sufficient during periods of transient loss of control in patients usually well controlled on diet.Repaglinide tablets doses are usually taken within 15 minutes of the meal but time may vary from immediately preceding the meal to as long as 30 minutes before the meal. Starting Dose For patients not previously treated or whose HbA1c is < 8%, the starting dose should be 0.5 mg with each meal. For patients previously treated with blood glucose-lowering drugs and whose HbA1c is ≥ 8%, the initial dose is 1 or 2 mg with each meal preprandially (see previous paragraph). Dose Adjustment Dosing adjustments should be determined by blood glucose response, usually fasting blood glucose. Postprandial glucose levels testing may be clinically helpful in patients whose pre-meal blood glucose levels are satisfactory but whose overall glycemic control (HbA1c) is inadequate. The preprandial dose should be doubled up to 4 mg with each meal until satisfactory blood glucose response is achieved. At least one week should elapse to assess response after each dose adjustment.The recommended dose range is 0.5 mg to 4 mg taken with meals. Repaglinide tablets may be dosed preprandially 2, 3, or 4 times a day in response to changes in the patient’s meal pattern. The maximum recommended daily dose is 16 mg. Patient Management Long-term efficacy should be monitored by measurement of HbA1c levels approximately every 3 months. Failure to follow an appropriate dosage regimen may precipitate hypoglycemia or hyperglycemia. Patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy including hypoglycemia. When hypoglycemia occurs in patients taking a combination of repaglinide tablets and a thiazolidinedione or repaglinide tablets and metformin, the dose of repaglinide tablets should be reduced. Patients Receiving Other Oral Hypoglycemic Agents When repaglinide tablets are used to replace therapy with other oral hypoglycemic agents, repaglinide tablets may be started on the day after the final dose is given. Patients should then be observed carefully for hypoglycemia due to potential overlapping of drug effects. When transferred from longer half-life sulfonylurea agents (e.g., chlorpropamide) to repaglinide, close monitoring may be indicated for up to one week or longer. Combination Therapy If repaglinide tablets monotherapy does not result in adequate glycemic control, metformin or a thiazolidinedione may be added. If metformin or thiazolidinedione monotherapy does not provide adequate control, repaglinide tablets may be added. The starting dose and dose adjustments for repaglinide tablets combination therapy is the same as for repaglinide tablets monotherapy. The dose of each drug should be carefully adjusted to determine the minimal dose required to achieve the desired pharmacologic effect. Failure to do so could result in an increase in the incidence of hypoglycemic episodes. Appropriate monitoring of FPG and HbA1c measurements should be used to ensure that the patient is not subjected to excessive drug exposure or increased probability of secondary drug failure.
Vidaza

Vidaza

Under no circumstances should ribavirin capsules be opened, crushed, or broken. Ribavirin capsules should be taken with food [see Clinical Pharmacology (12.3)]. Ribavirin capsules should not be used in patients with creatinine clearance less than 50 mL/min.

2.2 Ribavirin/INTRON A Combination Therapy

Adults Duration of Treatment – Interferon Alpha-naïve Patients The recommended dose of INTRON A is 3 million IU three times weekly subcutaneously. The recommended dose of ribavirin capsules depends on the patient’s body weight (refer to Table 3). The recommended duration of treatment for patients previously untreated with interferon is 24 to 48 weeks. The duration of treatment should be individualized to the patient depending on baseline disease characteristics, response to therapy, and tolerability of the regimen [see Indications and Usage (1.1), and Clinical Studies (14)]. After 24 weeks of treatment, virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV-RNA below the limit of detection of the assay by 24 weeks. There are no safety and efficacy data on treatment for longer than 48 weeks in the previously untreated patient population. Duration of Treatment – Re-treatment with INTRON A/Ribavirin in Relapse Patients In patients who relapse following nonpegylated interferon monotherapy, the recommended duration of treatment is 24 weeks.
Table 3: Recommended Dosing Body Weight Ribavirin Capsules ≤75 kg 2 x 200 mg capsules AM 3 x 200 mg capsules PM daily orally >75 kg 3 x 200 mg capsules AM 3 x 200 mg capsules PM daily orally
Pediatrics The recommended dose of ribavirin capsules is 15 mg/kg per day orally (divided dose AM and PM). INTRON A for Injection by body weight of 25 kg to 61 kg is 3 million IU/m2 three times weekly subcutaneously. The recommended duration of treatment is 48 weeks for pediatric patients with genotype 1. After 24 weeks of treatment, virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV-RNA below the limit of detection of the assay by this time. The recommended duration of treatment for pediatric patients with genotype 2/3 is 24 weeks.

2.3 Laboratory Tests

The following laboratory tests are recommended for all patients treated with ribavirin capsules, prior to beginning treatment and then periodically thereafter.
Standard hematologic tests - including hemoglobin (pretreatment, Week 2 and Week 4 of therapy, and as clinically appropriate [see Warnings and Precautions (5.2, 5.7)]), complete and differential white blood cell counts, and platelet count. Blood chemistries - liver function tests and TSH. Pregnancy - including monthly monitoring for women of childbearing potential. ECG [see Warnings and Precautions (5.2)].
2.4 Dose Modifications

If severe adverse reactions or laboratory abnormalities develop during combination ribavirin/INTRON A therapy, modify, or discontinue the dose until the adverse reaction abates or decreases in severity [see Warnings and Precautions (5)]. If intolerance persists after dose adjustment, combination therapy should be discontinued.

Ribavirin capsules should not be used in patients with creatinine clearance less than 50 mL/min. Patients with impaired renal function and those over the age of 50 should be carefully monitored with respect to development of anemia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5), and Clinical Pharmacology (12.3)].

Ribavirin capsules should be administered with caution to patients with pre-existing cardiac disease. Patients should be assessed before commencement of therapy and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be stopped [see Warnings and Precautions (5.2)].

For patients with a history of stable cardiovascular disease, a permanent dose reduction is required if the hemoglobin decreases by greater than or equal to 2 g/dL during any 4-week period. In addition, for these cardiac history patients, if the hemoglobin remains less than 12 g/dL after 4 weeks on a reduced dose, the patient should discontinue combination therapy.

It is recommended that a patient whose hemoglobin level falls below 10 g/dL have his/her ribavirin capsules dose modified or discontinued per Table 4 [see Warnings and Precautions(5.2)].
Table 4: Guidelines for Dose Modification and Discontinuation of Ribavirin in combination with INTRON A Based on Laboratory Parameters in Adults and Pediatrics Note 1: Adult patients: 1st dose reduction of ribavirin is by 200 mg/day (except in patients receiving the 1,400 mg, dose reduction should be by 400 mg/day). If needed, 2nd dose reduction of ribavirin is by an additional 200 mg/day. Patients whose dose of ribavirin is reduced to 600 mg daily receive one 200 mg capsule in the morning and two 200 mg capsules in the evening.Pediatric patients: 1st dose reduction of ribavirin is to 12 mg/kg/day, 2nd dose reduction of ribavirin is to 8 mg/kg/day. Note 2: For patients on ribavirin/INTRON A combination therapy: reduce INTRON A dose by 50%.* Pediatric patients who have pre-existing cardiac conditions and experience a hemoglobin decrease greater than or equal to 2 g/dL during any 4-week period during treatment should have weekly evaluations and hematology testing. † These guidelines are for patients with stable cardiac disease. Laboratory Parameters Reduce Ribavirin Daily Dose (see note 1) if: Reduce INTRON A Dose (see note 2) if: Discontinue Therapy if: WBC N/A 1 to <1.5 x 109/L <1 x 109/L Neutrophils N/A 0.5 to <0.75 x 109/L <0.5 x 109/L Platelets N/A 25 to < 50 x 109/L (adults) <25 x 109/L (adults) N/A 50 to <70 x 109/L (pediatrics) <50 x 109/L (pediatrics) Creatinine N/A N/A >2 mg/dL (pediatrics) Hemoglobin in patients without history of cardiac disease 8.5 to < 10 g/dL N/A <8.5 g/dL Reduce Ribavirin Dose by 200 mg/day and INTRON A Dose by Half if: Hemoglobin in patients with history of stable cardiac disease*† ≥2 g/dL decrease in hemoglobin during any four week period during treatment <8.5 g/dL or <12 g/dL after four weeks of dose reduction
Refer to labeling for INTRON A for additional information about how to reduce an INTRON A dose.
Vivacity

Vivacity

2.1 Hypertension

Use in Uncomplicated Hypertensive Patients: In patients with essential hypertension, the recommended initial dose is 4 mg once a day. The dose may be titrated, as needed to a maximum of 16 mg per day. The usual maintenance dose range is 4 mg to 8 mg administered as a single daily dose or in two divided doses. Use in Elderly Patients: The recommended initial daily dosage of perindopril erbumine tablets for the elderly is 4 mg daily, given in one or two divided doses. Experience with perindopril erbumine tablets is limited in the elderly at doses exceeding 8 mg. Dosages above 8 mg should be administered with careful blood pressure monitoring and dose titration [see Use in Specific Populations (8.5)]. Use with Diuretics: In patients who are currently being treated with a diuretic, symptomatic hypotension can occur following the initial dose of perindopril erbumine tablets. Consider reducing the dose of diuretic prior to starting perindopril erbumine tablets [see Drug Interactions (7.1)].

2.2 Stable Coronary Artery Disease

In patients with stable coronary artery disease, perindopril erbumine tablets should be given at an initial dose of 4 mg once daily for 2 weeks, and then increased as tolerated, to a maintenance dose of 8 mg once daily. In elderly patients (greater than 70 years), perindopril erbumine tablets should be given as a 2 mg dose once daily in the first week, followed by 4 mg once daily in the second week and 8 mg once daily for maintenance dose if tolerated.

2.3 Dose Adjustment in Renal Impairment and Dialysis

Perindoprilat elimination is decreased in renally impaired patients. Perindopril erbumine tablets are not recommended in patients with creatinine clearance <30 mL/min. For patients with lesser degrees of impairment, the initial dosage should be 2 mg/day and dosage should not exceed 8 mg/day. During dialysis, perindopril is removed with the same clearance as in patients with normal renal function.
Alendronate Sodium

Alendronate Sodium

2.1 Treatment of Osteoporosis in Postmenopausal Women

The recommended dosage is:
one 70 mg tablet once weekly
                                    or
one 10 mg tablet once daily
2.2 Prevention of Osteoporosis in Postmenopausal Women

The recommended dosage is:
one 35 mg tablet once weekly
                                    or
one 5 mg tablet once daily
2.3 Treatment to Increase Bone Mass in Men with Osteoporosis

The recommended dosage is:
one 70 mg tablet once weekly
                                    or
one 10 mg tablet once daily
2.4 Treatment of Glucocorticoid-Induced Osteoporosis

The recommended dosage is one 5 mg tablet once daily, except for postmenopausal women not receiving estrogen, for whom the recommended dosage is one 10 mg tablet once daily.

2.5 Treatment of Paget's Disease of Bone

The recommended treatment regimen is 40 mg once a day for six months. Re-treatment of Paget’s Disease Re-treatment with alendronate sodium tablets may be considered, following a six-month post-treatment evaluation period in patients who have relapsed, based on increases in serum alkaline phosphatase, which should be measured periodically. Re-treatment may also be considered in those who failed to normalize their serum alkaline phosphatase.

2.6 Important Administration Instructions

Instruct patients to do the following:
Take alendronate sodium tablets at least one-half hour before the first food, beverage, or medication of the day with plain water only [see Patient Counseling Information (17.2)]. Other beverages (including mineral water), food, and some medications are likely to reduce the absorption of alendronate sodium tablets [see Drug Interactions (7.1)]. Waiting less than 30 minutes, or taking alendronate sodium tablets with food, beverages (other than plain water) or other medications will lessen the effect of alendronate sodium tablets by decreasing its absorption into the body. Take alendronate sodium tablets upon arising for the day. To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation, an alendronate sodium tablet should be swallowed with a full glass of water (6 to 8 ounces). Patients should not lie down for at least 30 minutes and until after their first food of the day. Alendronate sodium tablets should not be taken at bedtime or before arising for the day. Failure to follow these instructions may increase the risk of esophageal adverse experiences [see Warnings and Precautions (5.1) and Patient Counseling Information (17.2)].
2.7 Recommendations for Calcium and Vitamin D Supplementation

Instruct patients to take supplemental calcium if dietary intake is inadequate [see Warnings and Precautions (5.2)]. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home-bound, or chronically ill) may need vitamin D supplementation. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.

2.8 Administration Instructions for Missed Doses

If a once-weekly dose of alendronate sodium tablets is missed, instruct patients to take one dose on the morning after they remember. They should not take two doses on the same day but should return to taking one dose once a week, as originally scheduled on their chosen day.
Amoxicillin

Amoxicillin

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. In some infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.
Table 1. Dosing Recommendations for Adult and Pediatric Patients > 3 Months of Age a Dosing for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections. b The children’s dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations. Infection Severitya Usual Adult Dose Usual Dose for Children > 3 Monthsb Ear/Nose/Throat Skin/Skin Structure Genitourinary Tract Mild/Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours Lower Respiratory Tract Mild/Moderate or Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours
2.2 Dosing in Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)

Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin capsules is 30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.

2.3 Dosing for H. pylori Infection

Triple Therapy: The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual Therapy: The recommended adult oral dose is 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days.Please refer to clarithromycin and lansoprazole full prescribing information.

2.4 Dosing in Renal Impairment
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of < 30 mL/min should not receive a 875 mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
Losartan Potassium

Losartan Potassium

Adult Hypertensive Patients Losartan potassium tablets USP may be administered with other antihypertensive agents, and with or without food.Dosing must be individualized. The usual starting dose of losartan potassium tablets USP is 50 mg once daily, with 25 mg used in patients with possible depletion of intravascular volume (e.g., patients treated with diuretics) (see WARNINGS, Hypotension ― Volume-Depleted Patients) and patients with a history of hepatic impairment (see PRECAUTIONS, General). Losartan potassium tablets USP can be administered once or twice daily with total daily doses ranging from 25 mg to 100 mg.If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3 to 6 weeks (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension).If blood pressure is not controlled by losartan potassium tablets USP alone, a low dose of a diuretic may be added. Hydrochlorothiazide has been shown to have an additive effect (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension).No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis. Pediatric Hypertensive Patients greater than or equal to 6 years of age The usual recommended starting dose is 0.7 mg/kg once daily (up to 50 mg total) administered as a tablet or a suspension (see Preparation of Suspension). Dosage should be adjusted according to blood pressure response. Doses above 1.4 mg/kg (or in excess of 100 mg) daily have not been studied in pediatric patients. (See CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Pharmacodynamics and Clinical Effects, and WARNINGS, Hypotension ― Volume-Depleted Patients.)Losartan potassium tablets USP are not recommended in pediatric patients less than 6 years of age or in pediatric patients with glomerular filtration rate less than 30 mL/min/1.73 m2 (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations, Pharmacodynamics and Clinical Effects, and PRECAUTIONS).

Preparation of Suspension (for 200 mL of a 2.5 mg/mL suspension)

Add 10 mL of Purified Water USP to an 8 ounce (240 mL) amber polyethylene terephthalate (PET) bottle containing ten 50 mg losartan potassium tablets USP. Immediately shake for at least 2 minutes. Let the concentrate stand for 1 hour and then shake for 1 minute to disperse the tablet contents. Separately prepare a 50/50 volumetric mixture of Ora-Plus™ and Ora-Sweet SF™. Add 190 mL of the 50/50 Ora-Plus™/Ora-Sweet SF™ mixture to the tablet and water slurry in the PET bottle and shake for 1 minute to disperse the ingredients. The suspension should be refrigerated at 2 to 8°C (36 to 46°F) and can be stored for up to 4 weeks. Shake the suspension prior to each use and return promptly to the refrigerator.Ora-Plus™ and Ora-Sweet SF™ are the trademarks of Paddock Laboratories, Inc.

Hypertensive Patients with Left Ventricular Hypertrophy

The usual starting dose is 50 mg of losartan potassium tablets USP once daily. Hydrochlorothiazide 12.5 mg daily should be added and/or the dose of losartan potassium tablets USP should be increased to 100 mg once daily followed by an increase in hydrochlorothiazide to 25 mg once daily based on blood pressure response (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke).

Nephropathy in Type 2 Diabetic Patients

The usual starting dose is 50 mg once daily. The dose should be increased to 100 mg once daily based on blood pressure response (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Nephropathy in Type 2 Diabetic Patients). Losartan potassium tablets USP may be administered with insulin and other commonly used hypoglycemic agents (e.g., sulfonylureas, glitazones and glucosidase inhibitors).
Cefadroxil

Cefadroxil

Cefadroxil is acid-stable and may be administered orally without regard to meals. Administration with food may be helpful in diminishing potential gastrointestinal complaints occasionally associated with oral cephalosporin therapy.

Adults

Urinary Tract Infections: For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.).For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d.). Skin and Skin Structure Infections: For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.). Pharyngitis and Tonsillitis: Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis—1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of cefadroxil should be administered for at least 10 days.

Renal Impairment

In patients with renal impairment, the dosage of cefadroxil should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of cefadroxil and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 m2]) is 500 mg at the time intervals listed below.
Creatinine Clearances Dosage Interval 0 to 10 mL/min 36 hours 10 to 25 mL/min 24 hours 25 to 50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.
Cefadroxil

Cefadroxil

Cefadroxil is acid-stable and may be administered orally without regard to meals. Administration with food may be helpful in diminishing potential gastrointestinal complaints occasionally associated with oral cephalosporin therapy.

Adults

Urinary Tract Infections: For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.). For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d.). Skin and Skin Structure Infections: For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.). Pharyngitis and Tonsillitis: Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis—1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of cefadroxil should be administered for at least 10 days. See chart for total daily dosage for children.
DAILY DOSAGE OF CEFADROXIL SUSPENSION Child’s Weight Ibs kg 250 mg/5 mL 500 mg/5 mL 10 4.5 ½ tsp 20 9.1 1 tsp 30 13.6 1½ tsp 40 18.2 2 tsp 1 tsp 50 22.7 2½ tsp 1¼ tsp 60 27.3 3 tsp 1½ tsp 70 & above 31.8+ — 2 tsp
Renal Impairment

In patients with renal impairment, the dosage of cefadroxil monohydrate should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of cefadroxil and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 m2]) is 500 mg at the time intervals listed below.
Creatinine Clearances Dosage Interval 0 to 10 mL/min 36 hours 10 to 25 mL/min 24 hours 25 to 50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.
Reconstitution Directions for Oral Suspension Bottle Size Reconstitution Directions 100 mL Suspend in a total of 60 mL water. Method: Tap bottle lightly to loosen powder. Add 60 mL of water in two portions. Shake well after each addition. 75 mL Suspend in a total of 45 mL water Method: Tap bottle lightly to loosen powder. Add 45 mL of water in two portions. Shake well after each addition. 50 mL Suspend in a total of 30 mL water Method: Tap bottle lightly to loosen powder. Add 30 mL of water in two portions. Shake well after each addition. After reconstitution, store in refrigerator. Shake well before using. Keep container tightly closed. Discard unused portion after 14 days.
Nevirapine

Nevirapine

2.1 Adult Patients

The recommended dose for nevirapine tablets is one 200 mg tablet daily for the first 14 days, followed by one 200 mg tablet twice daily, in combination with other antiretroviral agents. The lead-in period has been observed to decrease the incidence of rash. For concomitantly administered antiretroviral therapy, the manufacturer’s recommended dosage and monitoring should be followed.

2.2 Pediatric Patients

The recommended oral dose for pediatric patients 15 days and older is 150 mg/m2 once daily for 14 days followed by 150 mg/m2 twice daily thereafter. The total daily dose should not exceed 400 mg for any patient.

2.3 Monitoring of Patients

Intensive clinical and laboratory monitoring, including liver enzyme tests, is essential at baseline and during the first 18 weeks of treatment with nevirapine tablets. The optimal frequency of monitoring during this period has not been established. Some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, would include monitoring of liver enzyme tests at baseline, prior to dose escalation, and at two weeks post-dose escalation. After the initial 18-week period, frequent clinical and laboratory monitoring should continue throughout nevirapine tablets treatment [see Warnings and Precautions (5)]. In some cases, hepatic injury has progressed despite discontinuation of treatment.

2.4 Dosage Adjustment

Patients with Rash Discontinue nevirapine tablets if a patient experiences severe rash or any rash accompanied by constitutional findings [see Boxed Warning and Warnings and Precautions (5.2)] . Do not increase nevirapine tablets dose if a patient experiences mild to moderate rash without constitutional symptoms during the 14-day lead-in period of 200 mg/day (150 mg/m2/day in pediatric patients) until the rash has resolved [see Warnings and Precautions (5.2)]. The total duration of the once daily lead-in dosing period should not exceed 28 days at which point an alternative regimen should be sought. Patients with Hepatic Events If a clinical (symptomatic) hepatic event occurs, permanently discontinue nevirapine tablets. Do not restart nevirapine tablets after recovery [see Warnings and Precautions (5.1)].Patients with Dose Interruption For patients who interrupt nevirapine tablets dosing for more than 7 days, restart the recommended dosing, using one 200 mg tablet daily (150 mg/m2/day in pediatric patients) for the first 14 days (lead-in) followed by one 200 mg tablet twice daily (150 mg/m2 twice daily for pediatric patients).Patients with Renal Impairment Patients with CrCL greater than or equal to 20 mL per min do not require an adjustment in nevirapine tablets dosing. The pharmacokinetics of nevirapine have not been evaluated in patients with CrCL less than 20 mL per min. An additional 200 mg dose of nevirapine tablets following each dialysis treatment is indicated in patients requiring dialysis. Nevirapine metabolites may accumulate in patients receiving dialysis; however, the clinical significance of this accumulation is not known [see Clinical Pharmacology (12.3)].
Cefuroxime Axetil

Cefuroxime Axetil

NOTE: CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY).
Table 4. Cefuroxime Axetil Tablets (May be administered without regard to meals.) *The safety and effectiveness of cefuroxime axetil administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established. Population/Infection Dosage Duration(days) Adolescents and Adults (13 years and older) Pharyngitis/tonsillitis 250 mg b.i.d. 10 Acute bacterial maxillary sinusitis 250 mg b.i.d. 10 Acute bacterial exacerbations of chronic bronchitis 250 or 500 mg b.i.d. 10* Secondary bacterial infections of acute bronchitis 250 or 500 mg b.i.d. 5-10 Uncomplicated skin and skin-structure infections 250 or 500 mg b.i.d. 10 Uncomplicated urinary tract infections 250 mg b.i.d. 7-10 Uncomplicated gonorrhea 1,000 mg once single dose Early Lyme disease 500 mg b.i.d. 20 Pediatric Patients (who can swallow tablets whole) Acute otitis media 250 mg b.i.d. 10 Acute bacterial maxillary sinusitis 250 mg b.i.d. 10
Patients With Renal Failure

The safety and efficacy of cefuroxime axetil in patients with renal failure have not been established. Since cefuroxime is renally eliminated, its half-life will be prolonged in patients with renal failure.
Simvastatin

Simvastatin

2.1 Recommended Dosing

The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin tablets can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.

2.2 Restricted Dosing for 80 mg

Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80 mg dose of simvastatin tablets should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Warnings and Precautions (5.1)].Patients who are currently tolerating the 80 mg dose of simvastatin tablets who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80 mg dose of simvastatin tablets, patients unable to achieve their LDL-C goal utilizing the 40 mg dose of simvastatin tablets should not be titrated to the 80 mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.

2.3 Coadministration with Other Drugs

Patients taking Verapamil, Diltiazem, or Dronedarone
The dose of simvastatin tablets should not exceed 10 mg/day [see Warnings and Precautions (5.1), Drug Interactions (7.3), and Clinical Pharmacology (12.3)].
Patients taking Amiodarone, Amlodipine or Ranolazine
The dose of simvastatin tablets should not exceed 20 mg/day [see Warnings and Precautions (5.1), Drug Interactions (7.3), and Clinical Pharmacology (12.3)].
2.4 Patients with Homozygous Familial Hypercholesterolemia

The recommended dosage is 40 mg/day in the evening [see Dosage and Administration, Restricted Dosing for 80 mg (2.2)]. Simvastatin tablets should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of simvastatin tablets should be reduced by 50% if initiating lomitapide. Simvastatin tablets dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin tablets 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.

2.5 Adolescents (10 to 17 years of age) with Heterozygous Familial Hypercholesterolemia

The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy [see NCEP Pediatric Panel Guidelines1 and Clinical Studies (14.2)]. Adjustments should be made at intervals of 4 weeks or more.————————————1National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics. 89(3):495-501. 1992.

2.6 Patients with Renal Impairment

Because simvastatin tablets do not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal impairment. However, caution should be exercised when simvastatin tablets are administered to patients with severe renal impairment; such patients should be started at 5 mg/day and be closely monitored [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

2.7 Chinese Patients Taking Lipid-Modifying Doses (greater than or equal to 1 g/day Niacin) of Niacin-Containing Products

Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses (greater than or equal to 1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients. [See Warnings and Precautions (5.1).]
Topiramate

Topiramate

Dosage and Administration in Adults

Single Dose

Vaginal candidiasis: The recommended dosage of fluconazole for vaginal candidiasis is 150 mg as a single oral dose.

Multiple Dose

SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.The daily dose of fluconazole for the treatment of infections other than vaginal candidiasis should be based on the infecting organism and the patient’s response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse. Oropharyngeal candidiasis: The recommended dosage of fluconazole for oropharyngeal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of oropharyngeal candidiasis generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse. Esophageal candidiasis: The recommended dosage of fluconazole for esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms. Systemic Candida infections: For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used. Urinary tract infections and peritonitis: For the treatment of Candida urinary tract infections and peritonitis, daily doses of 50 to 200 mg have been used in open, noncomparative studies of small numbers of patients. Cryptococcal meningitis: The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. The recommended dosage of fluconazole for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily. Prophylaxis in patients undergoing bone marrow transplantation: The recommended fluconazole daily dosage for the prevention of candidiasis in patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start fluconazole prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Dosage and Administration in Children

The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients:
Pediatric Patients Adults * Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended. 3 mg/kg 100 mg 6 mg/kg 200 mg 12* mg/kg 400 mg
Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY.) Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole pharmacokinetics in full-term newborns is available. Oropharyngeal candidiasis: The recommended dosage of fluconazole for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse. Esophageal candidiasis: For the treatment of esophageal candidiasis, the recommended dosage of fluconazole in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms. Systemic Candida infections: For the treatment of candidemia and disseminated Candida infections, daily doses of 6 to 12 mg/kg/day have been used in an open, noncomparative study of a small number of children. Cryptococcal meningitis: For the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in children with AIDS, the recommended dose of fluconazole is 6 mg/kg once daily.

Dosage In Patients With Impaired Renal Function

Fluconazole is cleared primarily by renal excretion as unchanged drug. There is no need to adjust single dose therapy for vaginal candidiasis because of impaired renal function. In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table:
Creatinine Clearance (mL/min) Percent of Recommended Dose >50 100% ≤50 (no dialysis) 50% Regular dialysis 100% after each dialysis
Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition.When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults: Males: Weight (kg) x (140-age) ————————————— 72 x serum creatinine (mg/100 mL) Females: 0.85 × above valueAlthough the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children: K x linear length or height (cm) ————————————— serum creatinine (mg/100 mL) (Where K=0.55 for children older than 1 year and 0.45 for infants.)

Administration

Fluconazole tablets are administered orally. Fluconazole tablets can be taken with or without food.
Cefdinir

Cefdinir

(see INDICATIONS AND USAGEfor Indicated Pathogens)The recommended dosage and duration of treatment for infections in pediatric patients are described in the following chart; the total daily dose for all infections is 14 mg/kg, up to a maximum dose of 600 mg per day. Once-daily dosing for 10 days is as effective as BID dosing. Once-daily dosing has not been studied in skin infections; therefore, cefdinir for oral suspension should be administered twice daily in this infection. Cefdinir for oral suspension may be administered without regard to meals.
Pediatric Patients (Age 6 Months Through 12 Years) Type of Infection Dosage Duration    Acute Bacterial Otitis Media 7 mg/kg q12hor   14 mg/kg q24h       5 to 10 days   10 days    Acute Maxillary Sinusitis 7 mg/kg q12hor   14 mg/kg q24h    10 days10 days    Pharyngitis/Tonsillitis 7 mg/kg q12hor   14 mg/kg q24h       5 to 10 days   10 days    Uncomplicated Skin and Skin Structure Infections       7 mg/kg q12h    10 days CEFDINIR FOR ORAL SUSPENSION PEDIATRIC DOSAGE CHART a Pediatric patients who weight ≥ 43 kg should receive the maximum daily dose of 600 mg.       Weight 125 mg/5 mL 250 mg/5 mL 9 kg/20 lbs 2.5 mL q12h or 5 mL q24h Use 125 mg/5 mL product 18 kg/40 lbs 5 mL q12h or 10 mL q24h 2.5 mL q12h or 5 mL q24h 27 kg/60 lbs 7.5 mL q12h or 15 mL q24h 3.75 mL q12h or 7.5 mL q24h 36 kg/80 lbs 10 mL q12h or 20 mL q24h 5 mL q12h or 10 mL q24h ≥ 43 kga/95 lbs 12 mL q12h or 24 mL q24h 6 mL q12h or 12 mL q24h
Patients With Renal Insufficiency

For adult patients with creatinine clearance <30 mL/min, the dose of cefdinir should be 300 mg given once daily.Creatinine clearance is difficult to measure in outpatients. However, the following formula may be used to estimate creatinine clearance (CLcr) in adult patients. For estimates to be valid, serum creatinine levels should reflect steady-state levels of renal function.Males:              CLcr =     (weight) (140 – age)                                                 (72) (serum creatinine)Females:           CLcr = 0.85 x above valuewhere creatinine clearance is in mL/min, age is in years, weight is in kilograms, and serum creatinine is in mg/dL(3).The following formula may be used to estimate creatinine clearance in pediatric patients:CLcr =      K x  body length or height                             serum creatinineWhere K=0.55 for pediatric patients older than 1 year(4) and 0.45 for infants (up to 1 year)(5).In the above equation, creatinine clearance is in mL/min/1.73 m2, body length or height is in centimeters, and serum creatinine is in mg/dL.For pediatric patients with a creatinine clearance of <30 mL/min/1.73 m2, the dose of cefdinir should be 7 mg/kg (up to 300 mg) given once daily.

Patients on Hemodialysis

Hemodialysis removes cefdinir from the body. In patients maintained on chronic hemodialysis, the recommended initial dosage regimen is a 300 mg or 7 mg/kg dose every other day. At the conclusion of each hemodialysis session, 300 mg (or 7 mg/kg) should be given. Subsequent doses (300 mg or 7 mg/kg) are then administered every other day.
Directions for Mixing Cefdinir for Oral Suspension Final   Concentration       Final Volume   (mL)    Amount of   Water Directions    125 mg/5 mL    60100 38 mL63 mL    Tap bottle to loosen powder, then    add water in 2 portions. Shake well      after each aliquot.    250 mg/5 mL 60100 38 mL63 mL    Tap bottle to loosen powder, then    add water in 2 portions. Shake well      after each aliquot.
After mixing, the suspension can be stored at room temperature (25°C/77°F). The container should be kept tightly closed, and the suspension should be shaken well before each administration. The suspension may be used for 10 days, after which any unused portion must be discarded.
Cefpodoxime Proxetil Gr...

Cefpodoxime Proxetil Granule

(See INDICATIONS AND USAGE for indicated pathogens.) Cefpodoxime proxetil for oral suspension may be given without regard to food. The recommended dosages, durations of treatment, and applicable patient populations are as described in the following chart:
Adults and Adolescents (age 12 years and older): Type of Infection Total Daily Dose Dose Frequency Duration Pharyngitis and/or tonsillitis 200 mg 100 mg Q 12 hours 5 to 10 days Acute community-acquired pneumonia 400 mg 200 mg Q 12 hours 14 days Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women) 200 mg single dose Skin and skin structure 800 mg 400 mg Q 12 hours 7 to 14 days Acute maxillary sinusitis 400 mg 200 mg Q 12 hours 10 days Uncomplicated urinary tract infection 200 mg 100 mg Q 12 hours 7 days Infants and Pediatric Patients (age 2 months through 12 years): Type of Infection Total Daily Dose Dose Frequency Duration Acute otitis media 10 mg/kg/day(Max 400 mg/day) 5 mg/kg Q 12 h(Max 200 mg/dose) 5 days Pharyngitis and/or tonsillitis 10 mg/kg/day(Max 200 mg/day) 5 mg/kg/dose Q 12 h(Max 100 mg/dose) 5 to 10 days Acute maxillary sinusitis 10 mg/kg/day(Max 400 mg/day) 5 mg/kg Q 12 hours(Max 200 mg/dose) 10 days
Patients with Renal Dysfunction:

For patients with severe renal impairment (<30 mL/min creatinine clearance), the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to estimate creatinine clearance (mL/min). For this estimate to be valid, the serum creatinine level should represent a steady state of renal function. Males: Weight (kg) x (140 - age) (mL/min) 72 x serum creatinine (mg/100 mL) Females: 0.85 x above value (mL/min)

Patients with Cirrhosis:

Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) are similar to those in healthy subjects. Dose adjustment is not necessary in this population.

Directions for use:

Before reconstitution, remove the desiccant capsule by pulling out two small rings, then throw it.

Preparation of Suspension:
Constitution Directions For Oral Suspension Constituted Volume Final Concentration Directions 50 mL 50 mg per 5 mL Suspend in a total of 31 mL of distilled water. Method:First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 75 mL 50 mg per 5 mL Suspend in a total of 44 mL of distilled water. Method:First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 100 mL 50 mg per 5 mL Suspend in a total of 57 mL of distilled water. Method:First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 50 mL 100 mg per 5 mL Suspend in a total of 30 mL of distilled water. Method:First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 75 mL 100 mg per 5 mL Suspend in a total of 43 mL of distilled water. Method:First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 100 mL 100 mg per 5 mL Suspend in a total of 57 mL of distilled water. Method:First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water.
After mixing, the suspension should be stored in a refrigerator, 2° to 8°C (36° to 46°F). Shake well before using. Keep container tightly closed. The mixture may be used for 14 days. Discard unused portion after 14 days.
Finasteride

Finasteride

Finasteride tablets may be administered with or without meals.

2.1 Monotherapy

The recommended dose of finasteride tablets is one tablet (5 mg) taken once a day [see Clinical Studies (14.1)].

2.2 Combination with Alpha-Blocker

The recommended dose of finasteride tablets is one tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin [see Clinical Studies (14.2)].
Fluconazole

Fluconazole

Dosage and Administration in Adults

SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL (TABLETS AND SUSPENSION) AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.The daily dose of fluconazole for oral suspension for the treatment of infections should be based on the infecting organism and the patient’s response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse.Oropharyngeal candidiasisThe recommended dosage of fluconazole for oral suspension for oropharyngeal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of oropharyngeal candidiasis generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse.Esophageal candidiasisThe recommended dosage of fluconazole for oral suspension for esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms.Systemic Candida infectionsFor systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used.Urinary tract infections and peritonitisFor the treatment of Candida urinary tract infections and peritonitis, daily doses of 50 to 200 mg have been used in open, noncomparative studies of small numbers of patients.Cryptococcal meningitisThe recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. The recommended dosage of fluconazole for oral suspension for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily.Prophylaxis in patients undergoing bone marrow transplantationThe recommended fluconazole for oral suspension daily dosage for the prevention of candidiasis in patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start fluconazole for oral suspension prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Dosage and Administration in Children

The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients:
Pediatric Patients Adults * Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended. 3 mg/kg 100 mg 6 mg/kg 200 mg 12* mg/kg 400 mg
Experience with fluconazole for oral suspension in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY.) Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole for oral suspension pharmacokinetics in full-term newborns is available.Oropharyngeal candidiasisThe recommended dosage of fluconazole for oral suspension for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse.Esophageal candidiasisFor the treatment of esophageal candidiasis, the recommended dosage of fluconazole for oral suspension in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms.Systemic Candida infectionsFor the treatment of candidemia and disseminated Candida infections, daily doses of 6 to 12 mg/kg/day have been used in an open, noncomparative study of a small number of children.Cryptococcal meningitisFor the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in children with AIDS, the recommended dose of fluconazole for oral suspension is 6 mg/kg once daily.

Dosage In Patients With Impaired Renal Function

Fluconazole is cleared primarily by renal excretion as unchanged drug. In patients with impaired renal function who will receive multiple doses of fluconazole for oral suspension, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table:
Creatinine Clearance(mL/min) Percent ofRecommendedDose >50 100% ≤50 (no dialysis) 50% Regular dialysis 100% after each dialysis
Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition.When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults:Males: Weight (kg) x (140 – age) 72 x serum creatinine (mg/100 mL)Females: 0.85 × above valueAlthough the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children:K x linear length or height (cm) serum creatinine (mg/100 mL)(Where K=0.55 for children older than 1 year and 0.45 for infants.)

Administration

Fluconazole for oral suspension is administered orally. Fluconazole for oral suspension can be taken with or without food.

Directions for Mixing the Oral Suspension

Prepare a suspension at time of dispensing as follows: tap bottle until all the powder flows freely. To reconstitute, add 24 mL of distilled water or Purified Water (USP) to fluconazole bottle and shake vigorously to suspend powder. Each bottle will deliver 35 mL of suspension. The concentrations of the reconstituted suspensions are as follows:
Fluconazole Content per Bottle Concentration of Reconstituted Suspension 350 mg 10 mg/mL 1400 mg 40 mg/mL
Note: Shake oral suspension well before using. Store reconstituted suspension between 5°C (41°F) and 25°C (77°F). Protect from freezing.
Valsartan And Hydrochlo...

Valsartan And Hydrochlorothiazide

2.1 General Considerations

The usual starting dose is valsartan and hydrochlorothiazide tablets 160 mg/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 320 mg/25 mg tablet once daily as needed to control blood pressure [see Clinical Studies (14.2)]. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.

2.2 Add-On Therapy

A patient whose blood pressure is not adequately controlled with valsartan (or another ARB) alone or hydrochlorothiazide alone may be switched to combination therapy with valsartan and hydrochlorothiazide tablets.A patient who experiences dose-limiting adverse reactions on either component alone may be switched to valsartan and hydrochlorothiazide tablets containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to valsartan and hydrochlorothiazide tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 320 mg/25 mg.

2.3 Replacement Therapy

Valsartan and hydrochlorothiazide tablets may be substituted for the titrated components.

2.4 Initial Therapy

Valsartan and hydrochlorothiazide tablets are not recommended as initial therapy in patients with intravascular volume depletion [see Warnings and Precautions (5.2)].

2.5 Use with Other Antihypertensive Drugs

Valsartan and hydrochlorothiazide tablets may be administered with other antihypertensive agents.
Fluoxetine Solution

Fluoxetine Solution

2.1 Major Depressive Disorder

Initial Treatment Adult — Initiate fluoxetine oral solution 20 mg/day orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon).The maximum fluoxetine dose should not exceed 80 mg/day. In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 to 80 mg/day. Studies comparing fluoxetine 20, 40, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in Major Depressive Disorder in most cases [see Clinical Studies (14.1)]. Pediatric (children and adolescents) — Initiate fluoxetine oral solution 10 or 20 mg/day. After 1 week at 10 mg/day, increase the dose to 20 mg/day. However, due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day. Consider a dose increase to 20 mg/day after several weeks if insufficient clinical improvement is observed. In the short-term (8 to 9 week) controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Major Depressive Disorder, patients were administered fluoxetine doses of 10 to 20 mg/day [see Clinical Studies (14.1)]. All patients — As with other drugs effective in the treatment of Major Depressive Disorder, the full effect may be delayed until 4 weeks of treatment or longer.Periodically reassess to determine the need for maintenance treatment. Switching Patients to a Tricyclic Antidepressant (TCA) — Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Drug Interactions (7.7)].

2.2 Obsessive Compulsive Disorder

Initial Treatment Adult — Initiate fluoxetine oral solution 20 mg/day, orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon). A dose range of 20 to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose should not exceed 80 mg/day.In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20, 40, or 60 mg of fluoxetine or placebo [see Clinical Studies (14.2)]. In one of these studies, no dose-response relationship for effectiveness was demonstrated. Pediatric (children and adolescents) — In adolescents and higher weight children, initiate treatment with a dose of 10 mg/day. After 2 weeks, increase the dose to 20 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 60 mg/day is recommended.In lower weight children, initiate treatment with a dose of 10 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 30 mg/day is recommended. Experience with daily doses greater than 20 mg is very minimal, and there is no experience with doses greater than 60 mg.In the controlled clinical trial of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.2)].Periodically reassess to determine the need for treatment.

2.3 Bulimia Nervosa

Initial Treatment — Administer fluoxetine oral solution 60 mg/day in the morning. For some patients it may be advisable to titrate up to this target dose over several days. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with bulimia. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Bulimia Nervosa, patients were administered fixed daily fluoxetine doses of 20 or 60 mg, or placebo [see Clinical Studies (14.3)]. Only the 60 mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting.Periodically reassess to determine the need for maintenance treatment.

2.4 Panic Disorder

Initial Treatment — Initiate treatment with fluoxetine oral solution 10 mg/day. After one week, increase the dose to 20 mg/day. Consider a dose increase after several weeks if no clinical improvement is observed. Fluoxetine doses above 60 mg/day have not been systematically evaluated in patients with Panic Disorder. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Panic Disorder, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.4)]. The most frequently administered dose in the 2 flexible-dose clinical trials was 20 mg/day.Periodically reassess to determine the need for continued treatment.

2.7 Dosing in Specific Populations

Treatment of Pregnant Women — When treating pregnant women with fluoxetine oral solution, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding [see Use in Specific Populations (8.1)]. Geriatric — Consider a lower or less frequent dosage for the elderly [see Use in Specific Populations (8.5)]. Hepatic Impairment — As with many other medications, use a lower or less frequent dosage in patients with hepatic impairment [see Clinical Pharmacology (12.4) and Use in Specific Populations (8.6)]. Concomitant Illness — Patients with concurrent disease or on multiple concomitant medications may require dosage adjustments [see Clinical Pharmacology (12.4) and Warnings and Precautions (5.11)].

2.8 Discontinuation of Treatment

Symptoms associated with discontinuation of fluoxetine, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5.15)].

2.9 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with fluoxetine oral solution. Conversely, at least 5 weeks should be allowed after stopping fluoxetine oral solution before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.10 Use of Fluoxetine Oral Solution with Other MAOIs such as Linezolid or Methylene Blue

Do not start fluoxetine oral solution in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)].In some cases, a patient already receiving fluoxetine oral solution therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, fluoxetine oral solution should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with fluoxetine oral solution may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with fluoxetine oral solution is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].
Citalopram Hydrobromide...

Citalopram Hydrobromide Solution

Citalopram oral solution should be administered once daily, in the morning or evening, with or without food.Initial Treatment Citalopram oral solution should be administered at an initial dose of 20 mg once daily, with an increase to a maximum dose of 40 mg/day at an interval of no less than one week. Doses above 40 mg/day are not recommended due to the risk of QT prolongation. Additionally, the only study pertinent to dose response for effectiveness did not demonstrate an advantage for the 60 mg/day dose over the 40 mg/day dose. Special Populations 20 mg/day is the maximum recommended dose for patients who are greater than 60 years of age, patients with hepatic impairment, and for CYP2C19 poor metabolizers or those patients taking cimetidine or another CYP2C19 inhibitor (see WARNINGS).No dosage adjustment is necessary for patients with mild or moderate renal impairment. Citalopram oral solution should be used with caution in patients with severe renal impairment.Treatment of Pregnant Women During the Third Trimester Neonates exposed to citalopram oral solution and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with citalopram oral solution during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.Maintenance Treatment It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacologic therapy. Systematic evaluation of citalopram oral solution in two studies has shown that its antidepressant efficacy is maintained for periods of up to 24 weeks following 6 or 8 weeks of initial treatment (32 weeks total). In one study, patients were assigned randomly to placebo or to the same dose of citalopram oral solution (20 to 60 mg/day)during maintenance treatment as they had received during the acute stabilization phase, while in the other study, patients were assigned randomly to continuation of citalopram oral solution 20 or 40 mg/day, or placebo, for maintenance treatment. In the latter study, the rates of relapse to depression were similar for the two dose groups (see Clinical Trials under CLINICAL PHARMACOLOGY). Based on these limited data, it is not known whether the dose of citalopram needed to maintain euthymia is identical to the dose needed to induce remission. If adverse reactions are bothersome, a decrease in dose to 20 mg/day can be considered.

Discontinuation of Treatment with Citalopram Oral Solution

Symptoms associated with discontinuation of citalopram oral solution and other SSRIs and SNRIs have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with citalopram oral solution. Conversely, at least 14 days should be allowed after stopping citalopram oral solution before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).Use of Citalopram Oral Solution with Other MAOIs, Such as Linezolid or Methylene BlueDo not start citalopram oral solution in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving citalopram oral solution therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, citalopram oral solution should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with citalopram oral solution may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with citalopram oral solution is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).
Risperidone

Risperidone

Table 1. Recommended Daily Dosage by Indication Initial Dose Titration (Increments) Target Dose Effective Dose Range Schizophrenia: adults (2.1) 2 mg 1 to 2 mg 4 to 8 mg 4 to 16 mg Schizophrenia: adolescents (2.2) 0.5 mg 0.5 to 1 mg 3 mg 1 to 6 mg Bipolar mania: adults (2.2) 2 to 3 mg 1 mg 1 to 6 mg 1 to 6 mg Bipolar mania: children and adolescents (2.2) 0.5 mg 0.5 to 1 mg 1 to 2.5 mg 1 to 6 mg Irritability in autistic disorder (2.3) 0.25 mg Can increase to 0.5 mg by Day 4: (body weight less than 20 kg) 0.5 mg Can increase to 1 mg by Day 4: (body weight greater than or equal to 20 kg) After Day 4, at intervals of > 2 weeks: 0.25 mg (body weight less than 20 kg) 0.5 mg (body weight greater than or equal to 20 kg) 0.5 mg: (body weight less than 20 kg) 1 mg: (body weightgreater than or equal to 20 kg) 0.5 to 3 mg
Severe Renal and Hepatic Impairment in Adults: use a lower starting dose of 0.5 mg twice daily. May increase to dosages above 1.5 mg twice daily at intervals of one week or longer.

2.1 Schizophrenia

Adults Usual Initial Dose Risperidone tablets can be administered once or twice daily. Initial dosing is 2 mg per day. May increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg per day, as tolerated, to a recommended dose of 4 to 8 mg per day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 mg to 16 mg per day. However, doses above 6 mg per day for twice daily dosing were not demonstrated to be more efficacious than lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are generally not recommended. In a single study supporting once-daily dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg per day has not been evaluated in clinical trials [see Clinical Studies (14.1)].Adolescents The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to a recommended dose of 3 mg per day. Although efficacy has been demonstrated in studies of adolescent patients with schizophrenia at doses between 1 mg to 6 mg per day, no additional benefit was observed above 3 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.Maintenance Therapy While it is unknown how long a patient with schizophrenia should remain on risperidone tablets, the effectiveness of risperidone tablets 2 mg per day to 8 mg per day at delaying relapse was demonstrated in a controlled trial in adult patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years [see Clinical Studies (14.1)]. Both adult and adolescent patients who respond acutely should generally be maintained on their effective dose beyond the acute episode. Patients should be periodically reassessed to determine the need for maintenance treatment.Reinitiation of Treatment in Patients Previously Discontinued Although there are no data to specifically address reinitiation of treatment, it is recommended that after an interval off risperidone tablets, the initial titration schedule should be followed.Switching From Other Antipsychotics There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to risperidone tablets, or treating patients with concomitant antipsychotics.

2.2 Bipolar Mania

Usual DoseAdults The initial dose range is 2 mg to 3 mg per day. The dose may be adjusted at intervals of 24 hours or greater, in increments of 1 mg per day. The effective dose range is 1 mg to 6 mg per day, as studied in the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was demonstrated in a flexible dosage range of 1 mg to 6 mg per day [see Clinical Studies (14.2, 14.3)]. Risperidone tablets dose higher than 6 mg per day were not studied.Pediatrics The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to the recommended target dose of 1mg to 2.5 mg per day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 mg and 6 mg per day, no additional benefit was observed above 2.5 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.Maintenance Therapy There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of an acute manic episode with risperidone tablets. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of risperidone tablets in such longer-term treatment (i.e., beyond 3 weeks). The physician who elects to use risperidone tablets for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3 Irritability Associated with Autistic Disorder - Pediatrics (Children and Adolescents)

The dosage of risperidone tablets should be individualized according to the response and tolerability of the patient. The total daily dose of risperidone tablets can be administered once daily, or half the total daily dose can be administered twice daily.For patients with body weight less than 20 kg, initiate dosing at 0.25 mg per day. For patients with body weight greater than or equal to 20 kg, initiate dosing at 0.5 mg per day. After a minimum of four days, the dose may be increased to the recommended dose of 0.5 mg per day for patients less than 20 kg and 1 mg per day for patients greater than or equal to 20 kg. Maintain this dose for a minimum of 14 days. In patients not achieving sufficient clinical response, the dose may be increased at intervals of 2 weeks or greater, in increments of 0.25 mg per day for patients less than 20 kg, or increments of 0.5 mg per day for patients greater than or equal to 20 kg. The effective dose range is 0.5 mg to 3 mg per day. No dosing data are available for children who weigh less than 15 kg.Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of efficacy and safety. The physician who elects to use risperidone tablets for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime or administering half the daily dose twice daily, or a reduction of the dose.

2.4 Dosing in Patients with Severe Renal or Hepatic Impairment

For patients with severe renal impairment (CLcr < 30 mL/min) or hepatic impairment (10 to 15 points on Child Pugh System), the initial starting dose is 0.5 mg twice daily. The dose may be increased in increments of 0.5 mg or less, administered twice daily. For doses above 1.5 mg twice daily, increase in intervals of one week or greater [see Use in Specific Populations (8.6 and 8.7)].

2.5 Dose Adjustments for Specific Drug Interactions

When risperidone tablets are co-administered with enzyme inducers (e.g., carbamazepine), the dose of risperidone tablets should be increased up to double the patient's usual dose. It may be necessary to decrease the risperidone tablets dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1)]. Similar effect may be expected with co-administration of risperidone tablets with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).When fluoxetine or paroxetine is co-administered with risperidone tablets, the dose of risperidone tablets should be reduced. The risperidone tablets dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, risperidone tablets should be titrated slowly. It may be necessary to increase the risperidone tablets dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1)].
Levofloxacin

Levofloxacin

2.1 Dosage in Adult Patients with Normal Renal Function

The usual dose of levofloxacin tablets is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].
Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min) *   Due to the designated pathogens [see Indications and Usage (1)].† Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.‡   Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)].§   Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)].¶   This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia.#   This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli.Þ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)].ß   The safety of levofloxacin tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacintablets therapy should only be used when the benefit outweighs the risk.á Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Higher doses of levofloxacin tablets typically used for treatment of pneumonia can be used for treatment of plague, if clinically indicated. Type of Infection* Dosed Every 24 hours Duration (days)† Nosocomial Pneumonia 750 mg 7 to 14 Community Acquired Pneumonia‡ 500 mg 7 to 14 Community Acquired Pneumonia§ 750 mg 5 Acute Bacterial Sinusitis 750 mg 5 500 mg 10 to 14 Acute Bacterial Exacerbation of Chronic Bronchitis 500 mg 7 Complicated Skin and Skin Structure Infections (SSSI) 750 mg 7 to 14 Uncomplicated SSSI 500 mg 7 to 10 Chronic Bacterial Prostatitis 500 mg 28 Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)¶ 750 mg 5 Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)# 250 mg 10 Uncomplicated Urinary Tract Infection 250 mg 3 Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg Þ,ß Pediatric patients < 50 kg and ≥ 6 months of age Þ,ß 500 mgsee Table 2 below (2.2) 60 ß 60 ß Plague, adult and pediatric patients > 50 kgá Pediatric patients < 50 kg and ≥ 6 months of age 500 mg see Table 2 below (2.2) 10 to 14 10 to 14
2.2 Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.
Table 2: Dosage in Pediatric Patients ≥ 6 months of age Type of Infection* Dose Freq. Onceevery Duration† * Due to Bacillus anthracis [see Indications and Usage (1.13)] and Yersinia pestis [see Indications and Usage (1.14)]. † Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.‡ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)]. § The safety of levofloxacin tablets in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacin tablets therapy should only be used when the benefit outweighs the risk. ¶ Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Inhalational Anthrax (post-exposure)‡, §      Pediatric patients > 50 kg 500 mg 24 hr 60 days§      Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg (not to exceed 250 mg per dose) 12 hr 60 days§ Plague¶      Pediatric patients > 50 kg 500 mg 24 hr 10 to 14 days      Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg (not to exceed 250 mg per dose) 12 hr 10 to 14 days
2.3 Dosage Adjustment in Adults with Renal Impairment

Administer levofloxacin tablets with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.In patients with impaired renal function (creatinine clearance <50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations (8.6)].Table 3 shows how to adjust dose based on creatinine clearance.
Table 3: Dosage Adjustment in Adult Patients with Renal Impairment (creatinine clearance <50 mL/min) Dosage inNormal RenalFunction Every24 hours CreatinineClearance20 to 49 mL/min CreatinineClearance10 to 19 mL/min Hemodialysis orChronic AmbulatoryPeritoneal Dialysis(CAPD)    750 mg    750 mg every 48 hours    750 mg initial dose, then   500 mg every 48 hours    750 mg initial dose, then    500 mg every 48 hours    500 mg    500 mg initial dose, then    250 mg every 24 hours    500 mg initial dose, then   250 mg every 48 hours    500 mg initial dose, then    250 mg every 48 hours    250 mg    No dosage adjustment    required    250 mg every 48 hours.    If treating uncomplicated    UTI, then no dosage    adjustment is required    No information on    dosing adjustment is available
2.4 Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

Levofloxacin tablets should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Patient Counseling Information (17.2)].

2.5 Administration Instructions

Food and Levofloxacin Tablets Levofloxacin tablets can be administered without regard to food. Hydration for Patients Receiving Levofloxacin Tablets Adequate hydration of patients receiving oral levofloxacin tablets should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions (6.1) and Patient Counseling Information (17.2)].
Irbesartan

Irbesartan

Irbesartan tablets may be administered with other antihypertensive agents and with or without food. Hypertension The recommended initial dose of irbesartan tablets is 150 mg once daily. Patients requiring further reduction in blood pressure should be titrated to 300 mg once daily. A low dose of a diuretic may be added, if blood pressure is not controlled by irbesartan tablets alone. Hydrochlorothiazide has been shown to have an additive effect (see CLINICAL PHARMACOLOGY: Clinical Studies). Patients not adequately treated by the maximum dose of 300 mg once daily are unlikely to derive additional benefit from a higher dose or twice-daily dosing.No dosage adjustment is necessary in elderly patients, or in patients with hepatic impairment or mild to severe renal impairment. Nephropathy in Type 2 Diabetic Patients The recommended target maintenance dose is 300 mg once daily. There are no data on the clinical effects of lower doses of irbesartan tablets on diabetic nephropathy (see CLINICAL PHARMACOLOGY: Clinical Studies). Volume- and Salt-Depleted Patients A lower initial dose of irbesartan tablets (75 mg) is recommended in patients with depletion of intravascular volume or salt (e.g., patients treated vigorously with diuretics or on hemodialysis) (see WARNINGS: Hypotension in Volume- or Salt-Depleted Patients).
Alfuzosin Hydrochloride...

Alfuzosin Hydrochloride

The recommended dosage is one 10 mg alfuzosin hydrochloride extended release tablet once daily. The extent of absorption of alfuzosin is 50% lower under fasting conditions. Therefore, alfuzosin hydrochloride extended release tablets should be taken with food and with the same meal each day. The tablets should not be chewed or crushed.
Ciprofloxacin

Ciprofloxacin

Ciprofloxacin tablets should be administered orally as described in the appropriate Dosage Guidelines tables.

2.1 Dosage in Adults

The determination of dosage and duration for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient’s host-defense mechanisms, and the status of renal and hepatic function.
Table 1: Adult Dosage Guidelines 1.     Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure). 2.     Used in conjunction with metronidazole. 3.     Begin drug administration as soon as possible after suspected or confirmed exposure. Infection Dose Frequency Usual Durations1 Urinary Tract 250 to 500 mg every 12 hours 7 to 14 days Acute Uncomplicated Cystitis 250 mg every 12 hours 3 days Chronic Bacterial Prostatitis 500 mg every 12 hours 28 days Lower Respiratory Tract 500 to 750 mg every 12 hours 7 to 14 days Acute Sinusitis 500 mg every 12 hours 10 days Skin and Skin Structure 500 to 750 mg every 12 hours 7 to 14 days Bone and Joint 500 to 750 mg every 12 hours 4 to 8 weeks Complicated Intra–Abdominal2 500 mg every 12 hours 7 to 14 days Infectious Diarrhea 500 mg every 12 hours 5 to 7 days Typhoid Fever 500 mg every 12 hours 10 days Uncomplicated Urethral and Cervical Gonococcal Infections 250 mg single dose single dose Inhalational anthrax (post-exposure)3 500 mg every 12 hours 60 days Plague3 500 to 750 mg every 12 hours 14 days
Conversion of IV to Oral Dosing in Adults

Patients whose therapy is started with ciprofloxacin IV may be switched to ciprofloxacin tablets when clinically indicated at the discretion of the physician (Table 2) [see Clinical Pharmacology (12.3)].
Table 2: Equivalent AUC Dosing Regimens Ciprofloxacin Oral Dosage Equivalent Ciprofloxacin IV Dosage 250 mg Tablet every 12 hours 200 mg intravenous every 12 hours 500 mg Tablet every 12 hours 400 mg intravenous every 12 hours 750 mg Tablet every 12 hours 400 mg intravenous every 8 hours
2.2 Dosage in Pediatric Patients

Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined by the severity of the infection. Ciprofloxacin tablets should be administered as described in Table 3.
Table 3: Pediatric Dosage Guidelines 1.     The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). 2.     Begin drug administration as soon as possible after suspected or confirmed exposure. 3.     Begin drug administration as soon as possible after suspected or confirmed exposure to Y. pestis. Infection Dose Frequency Total Duration Complicated Urinary Tract or Pyelonephritis (patients from 1 to 17 years of age) 10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceeded even in patients weighing more than 51 kg) Every 12 hours 10 to 21 days1 Inhalational Anthrax (Post-Exposure)2 15 mg/kg (maximum 500 mg per dose) Every 12 hours 60 days Plague2,3 15 mg/kg (maximum 500 mg per dose) Every 12 to 8 hours 10 to 21 days
2.3 Dosage Modifications in Patients with Renal Impairment

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. Dosage guidelines for use in patients with renal impairment are shown in Table 4.
Table 4: Recommended Starting and Maintenance Doses for Adult Patients with Impaired Renal Function Creatinine Clearance (mL/min) Dose > 50 See Usual Dosage. 30 to 50 250 to 500 mg every12 hours 5 to 29 250 to 500 mg every 18 hours Patients on hemodialysis or Peritoneal dialysis 250 to 500 mg every 24 hours (after dialysis)
When only the serum creatinine concentration is known, the following formulas may be used to estimate creatinine clearance:

Men - Creatinine clearance (mL/min) =   Weight (kg) x (140–age)

                                                              72 x serum creatinine (mg/dL)

Women - 0.85 x the value calculated for men.

The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment, a unit dose of 750 mg may be administered at the intervals noted above. Patients should be carefully monitored.

Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of cUTI and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1.73 m2).

2.4 Important Administration Instructions

With Multivalent Cations

Administer ciprofloxacin tablets at least 2 hours before or 6 hours after magnesium/aluminum antacids; polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) or sucralfate; Videx® (didanosine) chewable/buffered tablets or pediatric powder for oral solution; other highly buffered drugs; or other products containing calcium, iron or zinc.

With Dairy Products

Concomitant administration of ciprofloxacin tablets with dairy products (like milk or yogurt) or calcium-fortified juices alone should be avoided since decreased absorption is possible; however, ciprofloxacin tablets may be taken with a meal that contains these products.

Hydration of Patients Receiving Ciprofloxacin Tablets

Assure adequate hydration of patients receiving ciprofloxacin tablets to prevent the formation of highly concentrated urine. Crystalluria has been reported with quinolones.

Instruct the patient of the appropriate ciprofloxacin tablets administration [see Patient Counseling Information (17)].
Irbesartan And Hydrochl...

Irbesartan And Hydrochlorothiazide

2.1 General Considerations

The side effects of irbesartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter [see Adverse Reactions (6)].Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.Irbesartan and hydrochlorothiazide tablets may be administered with or without food.Irbesartan and hydrochlorothiazide tablets may be administered with other antihypertensive agents. Renal impairment. The usual regimens of therapy with irbesartan and hydrochlorothiazide tablets may be followed as long as the patient’s creatinine clearance is >30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so irbesartan and hydrochlorothiazide tablets are not recommended. Hepatic impairment. No dosage adjustment is necessary in patients with hepatic impairment.

2.2 Add-On Therapy

In patients not controlled on monotherapy with irbesartan or hydrochlorothiazide, the recommended doses of irbesartan and hydrochlorothiazide tablets, in order of increasing mean effect, are (irbesartan-hydrochlorothiazide) 150 mg/12.5 mg, 300 mg/12.5 mg, and 300 mg/25 mg. The largest incremental effect will likely be in the transition from monotherapy to 150 mg/12.5 mg [see Clinical Studies (14.2)].

2.3 Replacement Therapy

Irbesartan and hydrochlorothiazide tablets may be substituted for the titrated components.

2.4 Initial Therapy

The usual starting dose is irbesartan and hydrochlorothiazide tablet 150 mg/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of 300 mg/25 mg once daily as needed to control blood pressure [see Clinical Studies (14.2)]. Irbesartan and hydrochlorothiazide tablets are not recommended as initial therapy in patients with intravascular volume depletion [see Warnings and Precautions (5.2)].
Doxorubicin Hydrochlori...

Doxorubicin Hydrochloride

2.1 Dosage for Postherpetic Neuralgia

In adults with postherpetic neuralgia, gabapentin capsules may be initiated on Day 1 as a single 300 mg dose, on Day 2 as 600 mg/day (300 mg two times a day), and on Day 3 as 900 mg/day (300 mg three times a day). The dose can subsequently be titrated up as needed for pain relief to a dose of 1800 mg/day (600 mg three times a day). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range; however, in these clinical studies, the additional benefit of using doses greater than 1800 mg/day was not demonstrated.

2.2 Dosage for Epilepsy with Partial Onset Seizures

Patients 12 years of age and above The starting dose is 300 mg three times a day. The recommended maintenance dose of gabapentin capsules is 300 mg to 600 mg three times a day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. Administer gabapentin capsules three times a day using 300 mg or 400 mg capsules. The maximum time between doses should not exceed 12 hours. Pediatric Patients Age 3 to 11 years The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the recommended maintenance dose reached by upward titration over a period of approximately 3 days. The recommended maintenance dose of gabapentin capsules in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses. The recommended maintenance dose of gabapentin capsules in patients 5 to 11 years of age is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

2.3 Dosage Adjustment in Patients with Renal Impairment

Dosage adjustment in patients 12 years of age and older with renal impairment or undergoing hemodialysis is recommended, as follows (see dosing recommendations above for effective doses in each indication):
TABLE1. Gabapentin capsules Dosage Based on Renal Funtion TID = Three times a day; BID = Two times a day; QD = Single daily dosea For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table. Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg) ≥ 60 900 to 3600 300 TID 400 TID 600 TID 800 TID 1200 TID >30 to 59 400 to 1400 200 BID 300 BID 400 BID 500 BID 700 BID >15 to 29 200 to 700 200 QD 300 QD 400 QD 500 QD 700 QD 15a 100 to 300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)b Hemodialysis 125 b 150 b 200 b 250 b 350 b
Creatinine clearance (CLCr) is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance can be reasonably well estimated using the equation of Cockcroft and Gault:

The use of gabapentin capsules in patients less than 12 years of age with compromised renal function has not been studied.

2.4 Dosage in Elderly

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.

2.5 Administration Information

Administer gabapentin capsules orally with or without food.Gabapentin capsules should be swallowed whole with water.If the gabapentin capsules dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).
Metoprolol Succinate

Metoprolol Succinate

2.1 General Considerations

The recommended initial dose of amlodipine and benazepril hydrochloride capsules is 1 capsule of amlodipine 2.5 mg and benazepril 10 mg orally once-daily.It is usually appropriate to begin therapy with amlodipine and benazepril hydrochloride capsules only after a patient has either (a) failed to achieve the desired antihypertensive effect with amlodipine or benazepril monotherapy, or (b) demonstrated inability to achieve adequate antihypertensive effect with amlodipine therapy without developing edema. The antihypertensive effect of amlodipine and benazepril hydrochloride capsules is largely attained within 2 weeks. If blood pressure remains uncontrolled, the dose may be titrated up to amlodipine 10 mg and benazepril 40 mg once-daily. The dosing should be individualized and adjusted according to the patient’s clinical response.Amlodipine is an effective treatment of hypertension in once-daily doses of 2.5 to 10 mg while benazepril is effective in doses of 10 to 80 mg. In clinical trials of amlodipine and benazepril combination therapy using amlodipine doses of 2.5 to 10 mg and benazepril doses of 10 to 40 mg, the antihypertensive effects increased with increasing dose of amlodipine in all patient groups, and the effects increased with increasing dose of benazepril in nonblack groups.

2.2 Dosage Adjustment in Renal Impairment

Renal Impairment: Amlodipine and benazepril hydrochloride capsules are not recommended in patients with creatinine clearance (CrCl) less than or equal to 30 mL/min. No dose adjustment of amlodipine and benazepril hydrochloride capsules is required in patients with CrCl greater than 30 mL/min/1.73m2 (serum creatinine roughly less than or equal to 3 mg/dL or 265 micromol/L) [see Warnings and Precautions (5.7), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].

2.3 Replacement Therapy

Amlodipine and benazepril hydrochloride capsules may be substituted for the titrated components.
Clindamycin Hydrochlori...

Clindamycin Hydrochloride

If significant diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING box).Adults Serious infections—150 to 300 mg every 6 hours. More severe infections—300 to 450 mg every 6 hours.Pediatric Patients Serious infections—8 to 16 mg/kg/day (4 to 8 mg/lb/day) divided into three or four equal doses. More severe infections—16 to 20 mg/kg/day (8 to 10 mg/lb/day) divided into three or four equal doses.To avoid the possibility of esophageal irritation, clindamycin hydrochloride capsules should be taken with a full glass of water.Serious infections due to anaerobic bacteria are usually treated with clindamycin injection. However, in clinically appropriate circumstances, the physician may elect to initiate treatment or continue treatment with clindamycin hydrochloride capsules.In cases of β-hemolytic streptococcal infections, treatment should continue for at least 10 days.
Venlafaxine Hydrochlori...

Venlafaxine Hydrochloride

Venlafaxine hydrochloride extended-release capsules should be administered in a single dose with food either in the morning or in the evening at approximately the same time each day. Each capsule should be swallowed whole with fluid and not divided, crushed, chewed, or placed in water, or it may be administered by carefully opening the capsule and sprinkling the entire contents on a spoonful of applesauce. This drug/food mixture should be swallowed immediately without chewing and followed with a glass of water to ensure complete swallowing of the pellets.

Initial Treatment

Major Depressive Disorder

For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release capsules is 75 mg/day, administered in a single dose. In the clinical trials establishing the efficacy of venlafaxine hydrochloride extended-release capsules in moderately depressed outpatients, the initial dose of venlafaxine was 75 mg/day. For some patients, it may be desirable to start at 37.5 mg/day for 4 to 7 days, to allow new patients to adjust to the medication before increasing to 75 mg/day. While the relationship between dose and antidepressant response for venlafaxine hydrochloride extended-release capsules has not been adequately explored, patients not responding to the initial 75 mg/day dose may benefit from dose increases to a maximum of approximately 225 mg/day. Dose increases should be in increments of up to 75 mg/day, as needed, and should be made at intervals of not less than 4 days, since steady state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4. In the clinical trials establishing efficacy, upward titration was permitted at intervals of 2 weeks or more; the average doses were about 140 to 180 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY).It should be noted that, while the maximum recommended dose for moderately depressed outpatients is also 225 mg/day for venlafaxine hydrochloride (immediate release), more severely depressed inpatients in one study of the development program for that product responded to a mean dose of 350 mg/day (range of 150 to 375 mg/day). Whether or not higher doses of venlafaxine hydrochloride extended-release capsules are needed for more severely depressed patients is unknown; however, the experience with venlafaxine hydrochloride extended-release capsules doses higher than 225 mg/day is very limited. (See PRECAUTIONS-General-Use in Patients With Concomitant Illness.)

Social Anxiety Disorder (Social Phobia)

The recommended dose is 75 mg/day, administered in a single dose. There was no evidence that higher doses confer any additional benefit. (See the Use in Patients With Concomitant Illness section of PRECAUTIONS.)Panic DisorderIt is recommended that initial single doses of 37.5 mg/day of venlafaxine hydrochloride extended-release capsules be used for 7 days. In clinical trials establishing the efficacy of venlafaxine hydrochloride extended-release capsules in outpatients with panic disorder, initial doses of 37.5 mg/day for 7 days were followed by doses of 75 mg/day and subsequent weekly dose increases of 75 mg/day to a maximum dose of 225 mg/day. Although a dose-response relationship for effectiveness in patients with panic disorder was not clearly established in fixed-dose studies, certain patients not responding to 75 mg/day may benefit from dose increases to a maximum of approximately 225 mg/day. Dose increases should be in increments of up to 75 mg/day, as needed, and should be made at intervals of not less than 7 days. (See the Use in Patients With Concomitant Illness section of PRECAUTIONS.)

Switching Patients from Venlafaxine Hydrochloride Tablets

Depressed patients who are currently being treated at a therapeutic dose with venlafaxine hydrochloride (immediate release) may be switched to venlafaxine hydrochloride extended-release capsules at the nearest equivalent dose (mg/day), e.g., 37.5 mg venlafaxine two-times-a-day to 75 mg venlafaxine hydrochloride extended-release capsules once daily. However, individual dosage adjustments may be necessary. Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI to treat psychiatric disorders and initiation of therapy with venlafaxine hydrochloride extended-release capsules. Conversely, at least 7 days should be allowed after stopping venlafaxine hydrochloride extended-release capsules before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS). Use of Venlafaxine Hydrochloride Extended-Release Capsules With Other MAOls, Such as Linezolid or Methylene Blue Do not start venlafaxine hydrochloride extended-release capsules in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving therapy with venlafaxine hydrochloride extended-release capsules may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, venlafaxine hydrochloride extended-release capsules should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with venlafaxine hydrochloride extended-release capsules may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with venlafaxine hydrochloride extended-release capsules is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to venlafaxine hydrochloride extended-release capsules, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with venlafaxine hydrochloride extended-release capsules during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Patients with Hepatic Impairment

Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared with normal subjects (see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Patients with Renal Impairment

Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared with normal subjects (see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose be reduced by 25% to 50%. In patients undergoing hemodialysis, it is recommended that the total daily dose be reduced by 50%. Because there was much individual variability in clearance between patients with renal impairment, individualization of dosage may be desirable in some patients.

Elderly Patients

No dose adjustment is recommended for elderly patients solely on the basis of age. As with any drug for the treatment of major depressive disorder, Social Anxiety Disorder, or panic disorder, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Maintenance Treatment

There is no body of evidence available from controlled trials to indicate how long patients with major depressive disorder, Social Anxiety Disorder, or panic disorder, should be treated with venlafaxine hydrochloride extended-release capsules.It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine hydrochloride extended-release capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine hydrochloride in maintaining a response in patients with recurrent major depressive disorder who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine hydrochloride for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see Clinical Trials under CLINICAL PHARMACOLOGY). Based on these limited data, it is not known whether or not the dose of venlafaxine hydrochloride/venlafaxine hydrochloride extended-release capsules needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.In patients with Social Anxiety Disorder, venlafaxine hydrochloride extended-release capsules have been shown to be effective in a 6-month clinical trial. The need for continuing medication in patients with Social Anxiety Disorder who improve with venlafaxine hydrochloride extended-release capsules treatment should be periodically reassessed.In a study of panic disorder in which patients responding during 12 weeks of acute treatment with venlafaxine hydrochloride extended-release capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day), patients continuing venlafaxine hydrochloride extended-release capsules experienced a significantly longer time to relapse than patients randomized to placebo. The need for continuing medication in patients with panic disorder who improve with venlafaxine hydrochloride extended-release capsules treatment should be periodically reassessed.

Discontinuing Venlafaxine Hydrochloride Extended-Release Capsules

Symptoms associated with discontinuation of venlafaxine hydrochloride extended-release capsules, other SNRIs, and SSRIs, have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. In clinical trials with venlafaxine hydrochloride extended-release capsules, tapering was achieved by reducing the daily dose by 75 mg at 1 week intervals. Individualization of tapering may be necessary.
Lisinopril

Lisinopril

2.1 Hypertension

Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect. Use with diuretics in adults If blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of lisinopril tablets.The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day. Pediatric Patients 6 years of age and older with hypertension For pediatric patients with glomerular filtration rate > 30 mL/min/1.73 m2, the recommended starting dose is 0.07 mg per kg once daily (up to 5 mg total). Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients [see Clinical Pharmacology (12.3)]. Lisinopril tablets is not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2 [see Use in Specific Populations (8.4) and Clinical Studies (14.1)].

2.2 Heart Failure

The recommended starting dose for lisinopril tablets, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension [see Warnings and Precautions (5.4), and Drug Interactions (7.1)]. The appearance of hypotension after the initial dose of lisinopril tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

2.3 Reduction of Mortality in Acute Myocardial Infarction

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give lisinopril tablets 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for at least six weeks.Initiate therapy with 2.5 mg in patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mmHg) during the first 3 days after the infarct [see Warnings and Precautions (5.4)]. If hypotension occurs (systolic blood pressure ≤ 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) lisinopril tablets should be withdrawn.

2.4 Dose in Patients with Renal Impairment

No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of lisinopril tablets to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2.5 mg. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Divalproex Sodium

Divalproex Sodium

2.1 Recommended Dosage

ADULTS

The recommended initial dose for patients not receiving a diuretic is 10 mg once a day. The usual maintenance dosage range is 20 mg to 40 mg per day administered as a single dose or in two equally divided doses. A dose of 80 mg gives an increased response, but experience with this dose is limited. The divided regimen was more effective in controlling trough (pre-dosing) blood pressure than the same dose given as a once-daily regimen.

Use with diuretics in adults

The recommended starting dose of benazepril hydrochloride tablets in a patient on a diuretic is 5 mg once daily. If blood pressure is not controlled with benazepril hydrochloride tablets alone, a low dose of diuretic may be added.

PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER

The recommended starting dose for pediatric patients is 0.2 mg/kg once per day. Titrate as needed to 0.6 mg/kg once per day. Doses above 0.6 mg/kg (or in excess of 40 mg daily) have not been studied in pediatric patients.

Benazepril hydrochloride tablets are not recommended in pediatric patients less than 6 years of age or in pediatric patients with GFR less than 30 mL/min/1.73m2[see Use in Specific Populations (8.4)].

2.2 Dose Adjustment for Renal Impairment

For adults with a GFR <30 mL/min/1.73 m2 (serum creatinine >3 mg/dL), the recommended initial dose is 5 mg benazepril hydrochloride tablet once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 40 mg. Benazepril hydrochloride tablets can also worsen renal function [see Warnings and Precautions (5.3)].

2.3 Preparation of Suspension (for 150 mL of a 2 mg/mL Suspension)

Add 75 mL of Ora-Plus®* oral suspending vehicle to an amber polyethylene terephthalate (PET) bottle containing fifteen benazepril hydrochloride 20 mg tablets, and shake for at least two minutes. Allow the suspension to stand for a minimum of 1 hour. After the standing time, shake the suspension for a minimum of one additional minute. Add 75 mL of Ora-Sweet®* oral syrup vehicle to the bottle and shake the suspension to disperse the ingredients. The suspension should be refrigerated at 2° to 8°C (36° to 46°F) and can be stored for up to 30 days in the PET bottle with a child-resistant screw-cap closure. Shake the suspension before each use.

*Ora-Plus® and Ora-Sweet® are registered trademarks of Paddock Laboratories, Inc. Ora Plus® contains carrageenan, citric acid, methylparaben, microcrystalline cellulose, carboxymethylcellulose sodium, potassium sorbate, simethicone, sodium phosphate monobasic, xanthan gum, and water. Ora-Sweet® contains citric acid, berry citrus flavorant, glycerin, methylparaben, potassium sorbate, sodium phosphate monobasic, sorbitol, sucrose, and water.
Lamotrigine

Lamotrigine

2.1 General Dosing Considerations

Rash There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be increased by (1) coadministration of lamotrigine tablets with valproate, (2) exceeding the recommended initial dose of lamotrigine tablets, or (3) exceeding the recommended dose escalation for lamotrigine tablets. However, cases have occurred in the absence of these factors [see Boxed Warning]. Therefore, it is important that the dosing recommendations be followed closely.

The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation for lamotrigine tablets is exceeded and in patients with a history of allergy or rash to other AEDs.

It is recommended that lamotrigine tablets not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine tablets, the need to restart with the initial dosing recommendations should be assessed. The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations. If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed. The half-life of lamotrigine is affected by other concomitant medications [see Clinical Pharmacology (12.3)].

Lamotrigine Tablets Added to Drugs Known to Induce or Inhibit Glucuronidation Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine. Drugs that induce glucuronidation include carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen-containing oral contraceptives, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Valproate inhibits glucuronidation. For dosing considerations for lamotrigine tablets in patients on estrogen-containing contraceptives and atazanavir/ritonavir, see below and Table 13. For dosing considerations for lamotrigine tablets in patients on other drugs known to induce or inhibit glucuronidation, see Table 1, Table 2, Table 5, Table 6, and Table 13.

Target Plasma Levels for Patients With Epilepsy or Bipolar Disorder A therapeutic plasma concentration range has not been established for lamotrigine. Dosing of lamotrigine tablets should be based on therapeutic response [see Clinical Pharmacology (12.3)].

Women Taking Estrogen-Containing Oral Contraceptives Starting Lamotrigine Tablets in Women Taking Estrogen-Containing Oral Contraceptives: Although estrogen-containing oral contraceptives have been shown to increase the clearance of lamotrigine [see Clinical Pharmacology (12.3)], no adjustments to the recommended dose-escalation guidelines for lamotrigine tablets should be necessary solely based on the use of estrogen-containing oral contraceptives. Therefore, dose escalation should follow the recommended guidelines for initiating adjunctive therapy with lamotrigine tablets based on the concomitant AED or other concomitant medications (see Table 1 or Table 5). See below for adjustments to maintenance doses of lamotrigine tablets in women taking estrogen-containing oral contraceptives.

Adjustments to the Maintenance Dose of Lamotrigine Tablets in Women Taking Estrogen-Containing Oral Contraceptives

(1) Taking Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine tablets will in most cases need to be increased by as much as 2-fold over the recommended target maintenance dose to maintain a consistent lamotrigine plasma level.

(2) Starting Estrogen-Containing Oral Contraceptives:In women taking a stable dose of lamotrigine tablets and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose will in most cases need to be increased by as much as 2-fold to maintain a consistent lamotrigine plasma level. The dose increases should begin at the same time that the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week. Dose increases should not exceed the recommended rate (see Table 1 or Table 5) unless lamotrigine plasma levels or clinical response support larger increases. Gradual transient increases in lamotrigine plasma levels may occur during the week of inactive hormonal preparation (pill-free week), and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation. Increased lamotrigine plasma levels could result in additional adverse reactions, such as dizziness, ataxia, and diplopia. If adverse reactions attributable to lamotrigine tablets consistently occur during the pill-free week, dose adjustments to the overall maintenance dose may be necessary. Dose adjustments limited to the pill-free week are not recommended. For women taking lamotrigine tablets in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine tablets should be necessary.

(3) Stopping Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine tablets will in most cases need to be decreased by as much as 50% in order to maintain a consistent lamotrigine plasma level. The decrease in dose of lamotrigine tablets should not exceed 25% of the total daily dose per week over a 2-week period, unless clinical response or lamotrigine plasma levels indicate otherwise [see Clinical Pharmacology (12.3)]. In women taking lamotrigine tablets in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine tablets should be necessary.

Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of lamotrigine has not been systematically evaluated. It has been reported that ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the progestin-only pills had no effect on lamotrigine plasma levels. Therefore, adjustments to the dosage of lamotrigine tablets in the presence of progestogens alone will likely not be needed.

Patients Taking Atazanavir/Ritonavir While atazanavir/ritonavir does reduce the lamotrigine plasma concentration, no adjustments to the recommended dose-escalation guidelines for lamotrigine tablets should be necessary solely based on the use of atazanavir/ritonavir. Dose escalation should follow the recommended guidelines for initiating adjunctive therapy with lamotrigine tablets based on concomitant AED or other concomitant medications (see Tables 1, 2, and 5). In patients already taking maintenance doses of lamotrigine tablets and not taking glucuronidation inducers, the dose of lamotrigine tablets may need to be increased if atazanavir/ritonavir is added, or decreased if atazanavir/ritonavir is discontinued [see Clinical Pharmacology (12.3)].

Patients With Hepatic Impairment Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study in 24 subjects with mild, moderate, and severe liver impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)], the following general recommendations can be made. No dosage adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be adjusted according to clinical response.

Patients With Renal Impairment Initial doses of lamotrigine tablets should be based on patients' concomitant medications (see Tables 1 to 3 or Table 5); reduced maintenance doses may be effective for patients with significant renal impairment [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)]. Few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine tablets. Because there is inadequate experience in this population, lamotrigine tablets should be used with caution in these patients.

Discontinuation Strategy Epilepsy: For patients receiving lamotrigine tablets in combination with other AEDs, a re-evaluation of all AEDs in the regimen should be considered if a change in seizure control or an appearance or worsening of adverse reactions is observed.

If a decision is made to discontinue therapy with lamotrigine tablets, a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.9)].

Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation should prolong the half-life of lamotrigine; discontinuing valproate should shorten the half-life of lamotrigine.

Bipolar Disorder: In the controlled clinical trials, there was no increase in the incidence, type, or severity of adverse reactions following abrupt termination of lamotrigine tablets. In clinical trials in patients with bipolar disorder, 2 patients experienced seizures shortly after abrupt withdrawal of lamotrigine tablets. However, there were confounding factors that may have contributed to the occurrence of seizures in these patients with bipolar disorder. Discontinuation of lamotrigine tablets should involve a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.9)].

2.2 Epilepsy - Adjunctive Therapy

This section provides specific dosing recommendations for patients older than 12 years and patients aged 2 to 12 years. Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AEDs or other concomitant medications (see Table 1 for patients older than 12 years and Table 2 for patients aged 2 to 12 years). A weight-based dosing guide for patients aged 2 to 12 years on concomitant valproate is provided in Table 3.

Patients Older Than 12 Years

Recommended dosing guidelines are summarized in Table 1.
Table 1. Escalation Regimen for Lamotrigine Tablets in Patients Older Than 12 Years With Epilepsy a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. In Patients TAKING Valproatea In Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea In Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 25 mg every other day 25 mg every day 50 mg/day Weeks 3 and 4 25 mg every day 50 mg/day 100 mg/day (in 2 divided doses) Week 5 onwardto maintenance Increase by 25 to50 mg/day every 1 to2 weeks. Increase by 50 mg/dayevery 1 to 2 weeks. Increase by100 mg/day every1 to 2 weeks. Usual maintenancedose 100 to 200 mg/day with valproate alone 100 to 400 mg/day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses) 225 to 375 mg/day (in 2 divided doses) 300 to 500 mg/day (in 2 divided doses)
Patients Aged 2 to 12 Years

Recommended dosing guidelines are summarized in Table 2.

Smaller starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by smaller starting doses and slower dose escalations. Therefore, maintenance doses will take longer to reach in clinical practice than in clinical trials. It may take several weeks to months to achieve an individualized maintenance dose. Maintenance doses in patients weighing less than 30 kg, regardless of age or concomitant AED, may need to be increased as much as 50%, based on clinical response.

Table 2. Escalation Regimen for Lamotrigine Tablets in Patients Aged 2 to 12 Years With Epilepsy Note: Only whole tablets should be used for dosing. a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. In Patients TAKING Valproatea In Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea In Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 0.15 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide) 0.3 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet Weeks 3 and 4 0.3 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide) 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet 1.2 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet Week 5 onward to maintenance The dose should be increased every 1 to 2 weeks as follows: calculate 0.3 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose. The dose should be increased every 1 to 2 weeks as follows: calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose. The dose should be increased every 1 to 2 weeks as follows: calculate 1.2 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose. Usualmaintenancedose 1 to 5 mg/kg/day (maximum 200 mg/day in1 or 2 divided doses)1 to 3 mg/kg/day withvalproate alone 4.5 to 7.5 mg/kg/day (maximum 300 mg/day in2 divided doses) 5 to 15 mg/kg/day (maximum400 mg/day in 2divided doses) Maintenance dose in patients less than 30 kg May need to be increasedby as much as 50%, basedon clinical response May need to be increasedby as much as 50%, basedon clinical response May need to beincreased by asmuch as 50%, basedon clinical response Table 3. The Initial Weight-Based Dosing Guide for Patients Aged 2 to 12 Years Taking Valproate (Weeks 1 to 4) With Epilepsy If the patient’s weight is Give this daily dose, using the most appropriate combination of lamotrigine 2 mg and 5 mg tablets Greater than And less than Weeks 1 and 2 Weeks 3 and 4 6.7 kg 14 kg 2 mg every other day 2 mg every day 14.1 kg 27 kg 2 mg every day 4 mg every day 27.1 kg 34 kg 4 mg every day 8 mg every day 34.1 kg 40 kg 5 mg every day 10 mg every day
Usual Adjunctive Maintenance Dose for Epilepsy:

The usual maintenance doses identified in Tables 1 and 2 are derived from dosing regimens employed in the placebo-controlled adjunctive trials in which the efficacy of lamotrigine tablets was established. In patients receiving multidrug regimens employing carbamazepine, phenytoin, phenobarbital, or primidone without valproate, maintenance doses of adjunctive lamotrigine tablets as high as 700 mg/day have been used. In patients receiving valproate alone, maintenance doses of adjunctive lamotrigine tablets as high as 200 mg/day have been used. The advantage of using doses above those recommended in Tables 1 to 4 has not been established in controlled trials.

2.3 Epilepsy - Conversion From Adjunctive Therapy to Monotherapy

The goal of the transition regimen is to attempt to maintain seizure control while mitigating the risk of serious rash associated with the rapid titration of lamotrigine tablets.

The recommended maintenance dose of lamotrigine tablets as monotherapy is 500 mg/day given in 2 divided doses.

To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations for lamotrigine tablets should not be exceeded [see Boxed Warning].

Conversion From Adjunctive Therapy With Carbamazepine, Phenytoin, Phenobarbital, or Primidone to Monotherapy With Lamotrigine Tablets After achieving a dose of 500 mg/day of lamotrigine tablets using the guidelines in Table 1, the concomitant enzyme-inducing AED should be withdrawn by 20% decrements each week over a 4-week period. The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial.

Conversion From Adjunctive Therapy With Valproate to Monotherapy With Lamotrigine Tablets The conversion regimen involves the 4 steps outlined in Table 4.
Table 4. Conversion From Adjunctive Therapy With Valproate to Monotherapy With Lamotrigine Tablets in Patients Aged 16 Years and Older With Epilepsy Lamotrigine Tablets Valproate Step 1 Achieve a dose of 200 mg/day according to guidelines in Table 1. Maintain established stable dose. Step 2 Maintain at 200 mg/day. Decrease dose by decrements no greater than 500 mg/day/week to 500 mg/day and then maintain for 1 week. Step 3 Increase to 300 mg/day and maintain for1 week. Simultaneously decrease to 250 mg/day and maintain for 1 week. Step 4 Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day. Discontinue.
Conversion From Adjunctive Therapy With Antiepileptic Drugs Other Than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy With Lamotrigine Tablets No specific dosing guidelines can be provided for conversion to monotherapy with lamotrigine tablets with AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate.

2.4 Bipolar Disorder

The goal of maintenance treatment with lamotrigine tablets is to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. The target dose of lamotrigine tablets is 200 mg/day (100 mg/day in patients taking valproate, which decreases the apparent clearance of lamotrigine, and 400 mg/day in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitor lopinavir/ritonavir that increase the apparent clearance of lamotrigine). In the clinical trials, doses up to 400 mg/day as monotherapy were evaluated; however, no additional benefit was seen at 400 mg/day compared with 200 mg/day [see Clinical Studies (14.2)]. Accordingly, doses above 200 mg/day are not recommended. Treatment with lamotrigine tablets is introduced, based on concurrent medications, according to the regimen outlined in Table 5. If other psychotropic medications are withdrawn following stabilization, the dose of lamotrigine tablets should be adjusted. For patients discontinuing valproate, the dose of lamotrigine tablets should be doubled over a 2-week period in equal weekly increments (see Table 6). For patients discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the dose of lamotrigine tablets should remain constant for the first week and then should be decreased by half over a 2-week period in equal weekly decrements (see Table 6). The dose of lamotrigine tablets may then be further adjusted to the target dose (200 mg) as clinically indicated.

If other drugs are subsequently introduced, the dose of lamotrigine tablets may need to be adjusted. In particular, the introduction of valproate requires reduction in the dose of lamotrigine tablets [see Drug Interactions (7), Clinical Pharmacology (12.3)].

To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of lamotrigine tablets should not be exceeded [see Boxed Warning].
Table 5. Escalation Regimen for Lamotrigine Tablets in Patients With Bipolar Disorder a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. In Patients TAKING Valproatea In Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea In Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 25 mg every other day 25 mg daily 50 mg daily Weeks 3 and 4 25 mg daily 50 mg daily 100 mg daily, in divided doses Week 5 50 mg daily 100 mg daily 200 mg daily, in divided doses Week 6 100 mg daily 200 mg daily 300 mg daily, in divided doses Week 7 100 mg daily 200 mg daily up to 400 mg daily, in divided doses Table 6. Dosage Adjustments to Lamotrigine Tablets in Patients With Bipolar Disorder Following Discontinuation of Psychotropic Medications a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. Discontinuation of Psychotropic Drugs (excluding Valproate,a Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb) After Discontinuation of Valproatea After Discontinuation of Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb Current dose of lamotrigine tablets (mg/day) 100 Current dose of lamotrigine tablets (mg/day) 400 Week 1 Maintain current dose of lamotrigine tablets 150 400 Week 2 Maintain current dose of lamotrigine tablets 200 300 Week 3 onward Maintain current dose of lamotrigine tablets 200 200
The benefit of continuing treatment in patients who had been stabilized in an 8- to 16-week open-label phase with lamotrigine tablets was established in 2 randomized, placebo-controlled clinical maintenance trials [see Clinical Studies (14.2 )]. However, the optimal duration of treatment with lamotrigine tablets has not been established. Thus, patients should be periodically reassessed to determine the need for maintenance treatment.
Topiramate

Topiramate

2.1 Epilepsy

It is not necessary to monitor topiramate plasma concentrations to optimize topiramate tablets therapy.

On occasion, the addition of topiramate tablets to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with topiramate tablets may require adjustment of the dose of topiramate tablets.

Because of the bitter taste, tablets should not be broken.

Topiramate tablets can be taken without regard to meals.

Monotherapy Use

Adults and Pediatric Patients 10 Years and Older

The recommended dose for topiramate monotherapy in adults and pediatric patients 10 years of age and older is 400 mg/day in two divided doses. Approximately 58% of patients randomized to 400 mg/day achieved this maximal dose in the monotherapy controlled trial; the mean dose achieved in the trial was 275 mg/day. The dose should be achieved by titration according to the following schedule (Table 1):
Table 1: Monotherapy Titration Schedule for Adults and Pediatric Patients 10 years and older Morning Dose Evening Dose Week 1 25 mg 25 mg Week 2 50 mg 50 mg Week 3 75 mg 75 mg Week 4 100 mg 100 mg Week 5 150 mg 150 mg Week 6 200 mg 200 mg
Children Ages 2 to <10 Years

Dosing of topiramate as initial monotherapy in children 2 to < 10 years of age with partial onset or primary generalized tonic-clonic seizures was based on a pharmacometric bridging approach [see Clinical Studies (14.1)].

Dosing in patients 2 to <10 years is based on weight. During the titration period, the initial dose of topiramate tablets should be 25 mg/day administered nightly for the first week. Based upon tolerability, the dosage can be increased to 50 mg/day (25 mg twice daily) in the second week. Dosage can be increased by 25 to 50 mg/day each subsequent week as tolerated. Titration to the minimum maintenance dose should be attempted over 5 to 7 weeks of the total titration period. Based upon tolerability and clinical response, additional titration to a higher dose (up to the maximum maintenance dose) can be attempted at 25 to 50 mg/day weekly increments. The total daily dose should not exceed the maximum maintenance dose for each range of body weight (Table 2).
Table 2: Monotherapy Target Total Daily Maintenance Dosing for Patients 2 to <10 Years * Administered in two equally divided doses Weight (kg) Total Daily Dose (mg/day)* Minimum Maintenance Dose Total Daily Dose (mg/day)* Maximum Maintenance Dose Up to 11 150 250 12 to 22 200 300 23 to 31 200 350 32 to 38 250 350 Greater than 38 250 400
Adjunctive Therapy Use Adults 17 Years of Age and Over - Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of topiramate tablets as adjunctive therapy in adults with partial onset seizures is 200 to 400 mg/day in two divided doses, and 400 mg/day in two divided doses as adjunctive treatment in adults with primary generalized tonic-clonic seizures. It is recommended that therapy be initiated at 25 to 50 mg/day followed by titration to an effective dose in increments of 25 to 50 mg/day every week. Titrating in increments of 25 mg/day every week may delay the time to reach an effective dose. Doses above 400 mg/day (600, 800 or 1,000 mg/day) have not been shown to improve responses in dose-response studies in adults with partial onset seizures. Daily doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose was reached at the end of 8 weeks [see Clinical Studies (14.1)] .

Pediatric Patients Ages 2 to 16 Years – Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of topiramate tablets as adjunctive therapy for pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 to 9 mg/kg/day in two divided doses. Titration should begin at 25 mg/day (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose of 6 mg/kg/day was reached at the end of 8 weeks [see Clinical Studies (14.1)] .

2.4 Patients with Renal Impairment

In renally impaired subjects (creatinine clearance less than 70 mL/min/1.73 m2), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.

2.5 Geriatric Patients (Ages 65 Years and Over)

Dosage adjustment may be indicated in the elderly patient when impaired renal function (creatinine clearance rate <70 mL/min/1.73 m2) is evident [see Clinical Pharmacology (12.3)].

2.6 Patients Undergoing Hemodialysis

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than a normal individual. Accordingly, a prolonged period of dialysis may cause topiramate concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed.

2.7 Patients with Hepatic Disease

In hepatically impaired patients, topiramate plasma concentrations may be increased. The mechanism is not well understood.
Lamotrigine

Lamotrigine

2.1 General Dosing Considerations

Rash There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be increased by (1) coadministration of lamotrigine tablets (chewable, dispersible) with valproate, (2) exceeding the recommended initial dose of lamotrigine tablets (chewable, dispersible), or (3) exceeding the recommended dose escalation for lamotrigine tablets (chewable, dispersible). However, cases have occurred in the absence of these factors [see Boxed Warning]. Therefore, it is important that the dosing recommendations be followed closely.

The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation for lamotrigine tablets (chewable, dispersible) is exceeded and in patients with a history of allergy or rash to other AEDs.

It is recommended that lamotrigine tablets (chewable, dispersible) not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine tablets (chewable, dispersible), the need to restart with the initial dosing recommendations should be assessed. The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations. If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed. The half-life of lamotrigine is affected by other concomitant medications [see Clinical Pharmacology (12.3)].

Lamotrigine Tablets (Chewable, Dispersible) Added to Drugs Known to Induce or Inhibit Glucuronidation Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine. Drugs that induce glucuronidation include carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen-containing oral contraceptives, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Valproate inhibits glucuronidation. For dosing considerations for lamotrigine tablets (chewable, dispersible) in patients on estrogen-containing contraceptives and atazanavir/ritonavir, see below and Table 13. For dosing considerations for lamotrigine tablets (chewable, dispersible) in patients on other drugs known to induce or inhibit glucuronidation, see Tables 1, 2, 5 to 6, and 13.

Target Plasma Levels for Patients with Epilepsy or Bipolar Disorder A therapeutic plasma concentration range has not been established for lamotrigine. Dosing of lamotrigine tablets (chewable, dispersible) should be based on therapeutic response [see Clinical Pharmacology (12.3)].

Women Taking Estrogen-Containing Oral Contraceptives Starting Lamotrigine Tablets (Chewable, Dispersible) in Women Taking Estrogen-Containing Oral Contraceptives: Although estrogen-containing oral contraceptives have been shown to increase the clearance of lamotrigine [see Clinical Pharmacology (12.3)], no adjustments to the recommended dose-escalation guidelines for lamotrigine tablets (chewable, dispersible) should be necessary solely based on the use of estrogen-containing oral contraceptives. Therefore, dose escalation should follow the recommended guidelines for initiating adjunctive therapy with lamotrigine tablets (chewable, dispersible) based on the concomitant AED or other concomitant medications (see Tables 1, 5, and 7). See below for adjustments to maintenance doses of lamotrigine tablets (chewable, dispersible) in women taking estrogen-containing oral contraceptives.

Adjustments to the Maintenance Dose of Lamotrigine Tablets (Chewable, Dispersible) in Women Taking Estrogen-Containing Oral Contraceptives:

(1) Taking Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine tablets (chewable, dispersible) will in most cases need to be increased by as much as 2-fold over the recommended target maintenance dose to maintain a consistent lamotrigine plasma level.

(2) Starting Estrogen-Containing Oral Contraceptives: In women taking a stable dose of lamotrigine tablets (chewable, dispersible) and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose will in most cases need to be increased by as much as 2-fold to maintain a consistent lamotrigine plasma level. The dose increases should begin at the same time that the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week. Dose increases should not exceed the recommended rate (see Tables 1 and 5) unless lamotrigine plasma levels or clinical response support larger increases. Gradual transient increases in lamotrigine plasma levels may occur during the week of inactive hormonal preparation (pill-free week), and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation. Increased lamotrigine plasma levels could result in additional adverse reactions, such as dizziness, ataxia, and diplopia. If adverse reactions attributable to lamotrigine tablets (chewable, dispersible) consistently occur during the pill-free week, dose adjustments to the overall maintenance dose may be necessary. Dose adjustments limited to the pill-free week are not recommended. For women taking lamotrigine tablets (chewable, dispersible) in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine tablets (chewable, dispersible) should be necessary.

(3) Stopping Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of lamotrigine tablets (chewable, dispersible) will in most cases need to be decreased by as much as 50% in order to maintain a consistent lamotrigine plasma level. The decrease in dose of lamotrigine tablets (chewable, dispersible) should not exceed 25% of the total daily dose per week over a 2-week period, unless clinical response or lamotrigine plasma levels indicate otherwise [see Clinical Pharmacology (12.3)]. In women taking lamotrigine tablets (chewable, dispersible) in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of lamotrigine tablets (chewable, dispersible) should be necessary.

Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of lamotrigine has not been systematically evaluated. It has been reported that ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the progestin-only pills had no effect on lamotrigine plasma levels. Therefore, adjustments to the dosage of lamotrigine tablets (chewable, dispersible) in the presence of progestogens alone will likely not be needed.

Patients Taking Atazanavir/Ritonavir While atazanavir/ritonavir does reduce the lamotrigine plasma concentration, no adjustments to the recommended dose-escalation guidelines for lamotrigine tablets (chewable, dispersible) should be necessary solely based on the use of atazanavir/ritonavir. Dose escalation should follow the recommended guidelines for initiating adjunctive therapy with lamotrigine tablets (chewable, dispersible) based on concomitant AED or other concomitant medications (see Tables 1, 2, and 5). In patients already taking maintenance doses of lamotrigine tablets (chewable, dispersible) and not taking glucuronidation inducers, the dose of lamotrigine tablets (chewable, dispersible) may need to be increased if atazanavir/ritonavir is added, or decreased if atazanavir/ritonavir is discontinued [see Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study in 24 subjects with mild, moderate, and severe liver impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)], the following general recommendations can be made. No dosage adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be adjusted according to clinical response.

Patients with Renal Impairment Initial doses of lamotrigine tablets (chewable, dispersible) should be based on patients’ concomitant medications (see Tables 1 to 3, and 5); reduced maintenance doses may be effective for patients with significant renal impairment [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)]. Few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine tablets (chewable, dispersible). Because there is inadequate experience in this population, lamotrigine tablets (chewable, dispersible) should be used with caution in these patients.

Discontinuation Strategy Epilepsy: For patients receiving lamotrigine tablets (chewable, dispersible) in combination with other AEDs, a re-evaluation of all AEDs in the regimen should be considered if a change in seizure control or an appearance or worsening of adverse reactions is observed.

If a decision is made to discontinue therapy with lamotrigine tablets (chewable, dispersible), a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.8)].

Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation should prolong the half-life of lamotrigine; discontinuing valproate should shorten the half-life of lamotrigine.

Bipolar Disorder: In the controlled clinical trials, there was no increase in the incidence, type, or severity of adverse reactions following abrupt termination of lamotrigine tablets (chewable, dispersible). In the clinical development program in adults with bipolar disorder, 2 patients experienced seizures shortly after abrupt withdrawal of lamotrigine tablets (chewable, dispersible). Discontinuation of lamotrigine tablets (chewable, dispersible) should involve a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.8)].

2.2 Epilepsy - Adjunctive Therapy

This section provides specific dosing recommendations for patients older than 12 years and patients aged 2 to 12 years. Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AEDs or other concomitant medications (see Table 1 for patients older than 12 years and Table 2 for patients aged 2 to 12 years). A weight-based dosing guide for patients aged 2 to 12 years on concomitant valproate is provided in Table 3. Patients Older than 12 Years Recommended dosing guidelines are summarized in Table 1.
Table 1. Escalation Regimen for Lamotrigine Tablets (Chewable, Dispersible) in Patients Older than 12 Years with Epilepsy a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. In Patients TAKING Valproatea In Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea In Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 25 mg every other day 25 mg every day 50 mg/day Weeks 3 and 4 25 mg every day 50 mg/day 100 mg/day (in 2 divided doses) Week 5 onward to maintenance Increase by 25 to50 mg/day every 1 to2 weeks. Increase by 50 mg/dayevery 1 to 2 weeks. Increase by100 mg/day every1 to 2 weeks. Usual maintenance dose 100 to 200 mg/day with valproate alone 100 to 400 mg/day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses) 225 to 375 mg/day (in 2 divided doses) 300 to 500 mg/day (in 2 divided doses)
Patients Aged 2 to 12 Years Recommended dosing guidelines are summarized in Table 2.Lower starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by lower starting doses and slower dose escalations. Therefore, maintenance doses will take longer to reach in clinical practice than in clinical trials. It may take several weeks to months to achieve an individualized maintenance dose. Maintenance doses in patients weighing less than 30 kg, regardless of age or concomitant AED, may need to be increased as much as 50%, based on clinical response.The smallest available strength of lamotrigine tablets (chewable, dispersible) is 2 mg, and only whole tablets should be administered. If the calculated dose cannot be achieved using whole tablets, the dose should be rounded down to the nearest whole tablet [see How Supplied/Storage and Handling (16) and Medication Guide].
Table 2. Escalation Regimen for Lamotrigine Tablets (Chewable, Dispersible) in Patients Aged 2 to 12 Years with Epilepsy Note: Only whole tablets should be used for dosing. a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. In Patients TAKING Valproatea In Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,b or Valproatea In Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 0.15 mg/kg/day in 1 or 2 divided doses,rounded down to the nearestwhole tablet (see Table 3 forweight-based dosing guide) 0.3 mg/kg/day in 1 or 2 divided doses,rounded down to the nearestwhole tablet 0.6 mg/kg/day in 2 divided doses,rounded down to thenearest whole tablet Weeks 3 and 4 0.3 mg/kg/day in 1 or 2 divided doses,rounded down to the nearestwhole tablet (see Table 3 forweight-based dosing guide) 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet 1.2 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet Week 5 onward to maintenance The dose should be increasedevery 1 to 2 weeks as follows:calculate 0.3 mg/kg/day,round this amount down tothe nearest whole tablet, andadd this amount to thepreviously administered dailydose. The dose should beincreased every 1 to 2 weeksas follows: calculate 0.6mg/kg/day, round thisamount down to the nearestwhole tablet, and add thisamount to the previouslyadministered daily dose. The dose should beincreased every 1 to 2weeks as follows: calculate1.2 mg/kg/day, round thisamount down to thenearest whole tablet, andadd this amount to thepreviously administereddaily dose. Usual maintenance dose 1 to 5 mg/kg/day (maximum 200 mg/day in1 or 2 divided doses)1 to 3 mg/kg/day withvalproate alone 4.5 to 7.5 mg/kg/day (maximum 300 mg/day in2 divided doses) 5 to 15 mg/kg/day (maximum400 mg/day in 2divided doses) Maintenance dose in patients less than 30 kg May need to be increasedby as much as 50%, basedon clinical response. May need to be increasedby as much as 50%, basedon clinical response. May need to beincreased by asmuch as 50%, basedon clinical response. Table 3. The Initial Weight-Based Dosing Guide for Patients Aged 2 to 12 Years Taking Valproate (Weeks 1 to 4) with Epilepsy If the patient’s weight is Give this daily dose, using the most appropriate combination of lamotrigine tablets (chewable, dispersible) 2 mg and 5 mg Greater than And less than Weeks 1 and 2 Weeks 3 and 4 6.7 kg 14 kg 2 mg every other day 2 mg every day 14.1 kg 27 kg 2 mg every day 4 mg every day 27.1 kg 34 kg 4 mg every day 8 mg every day 34.1 kg 40 kg 5 mg every day 10 mg every day
Usual Adjunctive Maintenance Dose for Epilepsy The usual maintenance doses identified in Tables 1 and 2 are derived from dosing regimens employed in the placebo-controlled adjunctive trials in which the efficacy of lamotrigine tablets (chewable, dispersible) was established. In patients receiving multidrug regimens employing carbamazepine, phenytoin, phenobarbital, or primidone without valproate, maintenance doses of adjunctive lamotrigine tablets (chewable, dispersible) as high as 700 mg/day have been used. In patients receiving valproate alone, maintenance doses of adjunctive lamotrigine tablets (chewable, dispersible) as high as 200 mg/day have been used. The advantage of using doses above those recommended in Tables 1 to 4 has not been established in controlled trials.

2.3 Epilepsy - Conversion from Adjunctive Therapy to Monotherapy

The goal of the transition regimen is to attempt to maintain seizure control while mitigating the risk of serious rash associated with the rapid titration of lamotrigine tablets (chewable, dispersible).

The recommended maintenance dose of lamotrigine tablets (chewable, dispersible) as monotherapy is 500 mg/day given in 2 divided doses.

To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations for lamotrigine tablets (chewable, dispersible) should not be exceeded [see Boxed Warning]. Conversion from Adjunctive Therapy with Carbamazepine, Phenytoin, Phenobarbital, or Primidone to Monotherapy with Lamotrigine Tablets (Chewable, Dispersible) After achieving a dose of 500 mg/day of lamotrigine tablets (chewable, dispersible) using the guidelines in Table 1, the concomitant enzyme-inducing AED should be withdrawn by 20% decrements each week over a 4-week period. The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial. Conversion from Adjunctive Therapy with Valproate to Monotherapy with Lamotrigine Tablets (Chewable, Dispersible) The conversion regimen involves the 4 steps outlined in Table 4.
Table 4. Conversion from Adjunctive Therapy with Valproate to Monotherapy with Lamotrigine Tablets (Chewable, Dispersible) in Patients Aged 16 Years and Older with Epilepsy Lamotrigine Tablets (Chewable, Dispersible) Valproate Step 1 Achieve a dose of 200 mg/day according to guidelines in Table 1. Maintain established stable dose. Step 2 Maintain at 200 mg/day. Decrease dose by decrements no greater than 500 mg/day/week to 500 mg/day and then maintain for 1 week. Step 3 Increase to 300 mg/day and maintain for1 week. Simultaneously decrease to 250 mg/day and maintain for 1 week. Step 4 Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day. Discontinue.
Conversion from Adjunctive Therapy with Antiepileptic Drugs other than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy with Lamotrigine Tablets (Chewable, Dispersible) No specific dosing guidelines can be provided for conversion to monotherapy with lamotrigine tablets (chewable, dispersible) with AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate.

2.4 Bipolar Disorder

The goal of maintenance treatment with lamotrigine tablets (chewable, dispersible) is to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy [see Indications and Usage (1)].Patients taking lamotrigine tablets (chewable, dispersible) for more than 16 weeks should be periodically reassessed to determine the need for maintenance treatment. Adults The target dose of lamotrigine tablets (chewable, dispersible) is 200 mg/day (100 mg/day in patients taking valproate, which decreases the apparent clearance of lamotrigine, and 400 mg/day in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitor lopinavir/ritonavir that increase the apparent clearance of lamotrigine). In the clinical trials, doses up to 400 mg/day as monotherapy were evaluated; however, no additional benefit was seen at 400 mg/day compared with 200 mg/day [see Clinical Studies (14.2)]. Accordingly, doses above 200 mg/day are not recommended.Treatment with lamotrigine tablets (chewable, dispersible) is introduced, based on concurrent medications, according to the regimen outlined in Table 5. If other psychotropic medications are withdrawn following stabilization, the dose of lamotrigine tablets (chewable, dispersible) should be adjusted. In patients discontinuing valproate, the dose of lamotrigine tablets (chewable, dispersible) should be doubled over a 2-week period in equal weekly increments (see Table 6). In patients discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the dose of lamotrigine tablets (chewable, dispersible) should remain constant for the first week and then should be decreased by half over a 2-week period in equal weekly decrements (see Table 6). The dose of lamotrigine tablets (chewable, dispersible) may then be further adjusted to the target dose (200 mg) as clinically indicated.

If other drugs are subsequently introduced, the dose of lamotrigine tablets (chewable, dispersible) may need to be adjusted. In particular, the introduction of valproate requires reduction in the dose of lamotrigine tablets (chewable, dispersible) [see Drug Interactions (7), Clinical Pharmacology (12.3)].To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of lamotrigine tablets (chewable, dispersible) should not be exceeded [see Boxed Warning].
Table 5. Escalation Regimen for Lamotrigine Tablets (Chewable, Dispersible) in Adults with Bipolar Disorder a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. In Patients TAKING Valproatea In Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidoneb,or Valproatea In Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb and NOT TAKING Valproatea Weeks 1 and 2 25 mg every other day 25 mg daily 50 mg daily Weeks 3 and 4 25 mg daily 50 mg daily 100 mg daily, in divided doses Week 5 50 mg daily 100 mg daily 200 mg daily, in divided doses Week 6 100 mg daily 200 mg daily 300 mg daily, in divided doses Week 7 100 mg daily 200 mg daily up to 400 mg daily, in divided doses Table 6. Dosage Adjustments to Lamotrigine Tablets (Chewable, Dispersible) in Adults with Bipolar Disorder Following Discontinuation of Psychotropic Medications a Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].b Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7), and Clinical Pharmacology (12.3)]. Discontinuation of Psychotropic Drugs (excluding Valproate,a Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb) After Discontinuation of Valproatea After Discontinuation of Carbamazepine, Phenytoin, Phenobarbital, or Primidoneb Current Dose of lamotrigine tablets (chewable, dispersible) (mg/day) 100 Current Dose of lamotrigine tablets (chewable, dispersible) (mg/day) 400 Week 1 Maintain current dose of lamotrigine tablets (chewable, dispersible) 150 400 Week 2 Maintain current dose of lamotrigine tablets (chewable, dispersible) 200 300 Week 3 onward Maintain current dose of lamotrigine tablets (chewable, dispersible) 200 200
2.5 Administration of Lamotrigine Tablets (Chewable, Dispersible)

Lamotrigine tablets (chewable, dispersible) may be swallowed whole, chewed, or dispersed in water or diluted fruit juice. If the tablets are chewed, consume a small amount of water or diluted fruit juice to aid in swallowing.To disperse lamotrigine tablets (chewable, dispersible), add the tablets to a small amount of liquid (1 teaspoon, or enough to cover the medication). Approximately 1 minute later, when the tablets are completely dispersed, swirl the solution and consume the entire quantity immediately. No attempt should be made to administer partial quantities of the dispersed tablets.
Pennsaid

Pennsaid

Divalproex sodium delayed-release tablets are intended for oral administration. Divalproex sodium delayed-release tablets should be swallowed whole and should not be crushed or chewed.Patients should be informed to take divalproex sodium delayed-release tablets every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.

2.1 Mania

Divalproex sodium delayed-release tablets are administered orally. The recommended initial dose is 750 mg daily in divided doses. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In placebo-controlled clinical trials of acute mania, patients were dosed to a clinical response with a trough plasma concentration between 50 and 125 mcg/mL. Maximum concentrations were generally achieved within 14 days. The maximum recommended dosage is 60 mg/kg/day.There is no body of evidence available from controlled trials to guide a clinician in the longer term management of a patient who improves during divalproex sodium delayed-release tablets treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no data to support the benefits of divalproex sodium delayed-release tablets in such longer-term treatment. Although there are no efficacy data that specifically address longer-term antimanic treatment with divalproex sodium delayed-release tablets, the safety of divalproex sodium delayed-release tablets in long-term use is supported by data from record reviews involving approximately 360 patients treated with divalproex sodium delayed-release tablets for greater than 3 months.

2.2 Epilepsy

Divalproex sodium delayed-release tablets are administered orally. Divalproex sodium delayed-release tablets are indicated as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures. As the divalproex sodium delayed-release tablets dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions (7.2)].Complex Partial Seizures For adults and children 10 years of age or older.Monotherapy (Initial Therapy) Divalproex sodium delayed-release tablets have not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.Conversion to Monotherapy Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of divalproex sodium delayed-release tablets therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.Adjunctive Therapy Divalproex sodium delayed-release tablets may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. If the total daily dose exceeds 250 mg, it should be given in divided doses.In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to valproate, no adjustment of carbamazepine or phenytoin dosage was needed [see Clinical Studies (14.2)]. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see Drug Interactions (7)].Simple and Complex Absence Seizures The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. If the total daily dose exceeds 250 mg, it should be given in divided doses.A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentrations for most patients with absence seizures is considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see Clinical Pharmacology (12.3)].As the divalproex sodium delayed-release tablets dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see Drug Interactions (7.2)].Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.In epileptic patients previously receiving valproic acid therapy, divalproex sodium delayed-release tablets should be initiated at the same daily dose and dosing schedule. After the patient is stabilized on divalproex sodium delayed-release tablets, a dosing schedule of two or three times a day may be elected in selected patients.

2.3 Migraine

Divalproex sodium delayed-release tablets are indicated for prophylaxis of migraine headaches in adults.Divalproex sodium delayed-release tablets are administered orally. The recommended starting dose is 250 mg twice daily. Some patients may benefit from doses up to 1,000 mg/day. In the clinical trials, there was no evidence that higher doses led to greater efficacy.

2.4 General Dosing Advice

Dosing in Elderly Patients Due to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see Warnings and Precautions (5.14), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].Dose-Related Adverse Reactions The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see Warnings and Precautions (5.8)]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.G.I. Irritation Patients who experience G.I. irritation may benefit from administration of the drug with food or by slowly building up the dose from an initial low level.
Citalopram

Citalopram

Citalopram tablets

should be administered once daily, in the morning or evening, with or without food.

Initial Treatment

Citalopram tablets

should be administered at an initial dose of 20 mg once daily, with an increase to a maximum dose of 40 mg/day at an interval of no less than one week. Doses above 40 mg/day are not recommended due to the risk of QT prolongation. Additionally, the only study pertinent to dose response for effectiveness did not demonstrate an advantage for the 60 mg/day dose over the 40 mg/day dose.

Special Populations

20 mg/day is the maximum recommended dose for patients who are greater than 60 years of age, patients with hepatic impairment, and for CYP2C19 poor metabolizers or those patients taking cimetidine or another CYP2C19 inhibitor (see WARNINGS).No dosage adjustment is necessary for patients with mild or moderate renal impairment. Citalopram tablets should be used with caution in patients with severe renal impairment.

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to citalopram tablets and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with citalopram tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Maintenance Treatment

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacologic therapy. Systematic evaluation of citalopram tablets in two studies have shown that its antidepressant efficacy is maintained for periods of up to 24 weeks following 6 or 8 weeks of initial treatment (32 weeks total). In one study, patients were assigned randomly to placebo or to the same dose of citalopram tablets (20 to 60 mg/day) during maintenance treatment as they had received during the acute stabilization phase, while in the other study, patients were assigned randomly to continuation of citalopram tablets 20 or 40 mg/day, or placebo, for maintenance treatment. In the latter study, the rates of relapse to depression were similar for the two dose groups (see Clinical Trials under CLINICAL PHARMACOLOGY). Based on these limited data, it is not known whether the dose of citalopram needed to maintain euthymia is identical to the dose needed to induce remission. If adverse reactions are bothersome, a decrease in dose to 20 mg/day can be considered.

Discontinuation of Treatment with Citalopram Tablets

Symptoms associated with discontinuation of citalopram tablets and other SSRIs and SNRIs have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with citalopram tablets. Conversely, at least 14 days should be allowed after stopping citalopram tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Citalopram Tablets with Other MAOIs, Such as Linezolid or Methylene Blue

Do not start citalopram tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS). In some cases, a patient already receiving citalopram tablets therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, citalopram tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with citalopram tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS). The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with citalopram tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).
Escitalopram

Escitalopram

Escitalopram tablets should be administered once daily, in the morning or evening, with or without food.

2.1 Major Depressive Disorder

Initial Treatment Adolescents The recommended dose of escitalopram tablets is 10 mg once daily. A flexible-dose trial of escitalopram tablets (10 to 20 mg/day) demonstrated the effectiveness of escitalopram tablets [see Clinical Studies (14.1)]. If the dose is increased to 20 mg, this should occur after a minimum of three weeks.Adults The recommended dose of escitalopram tablets is 10 mg once daily. A fixed-dose trial of escitalopram tablets demonstrated the effectiveness of both 10 mg and 20 mg of escitalopram tablets, but failed to demonstrate a greater benefit of 20 mg over 10 mg [see Clinical Studies (14.1)]. If the dose is increased to 20 mg, this should occur after a minimum of one week. Maintenance Treatment It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of continuing escitalopram tablets 10 or 20 mg/day in adults patients with major depressive disorder who responded while taking escitalopram tablets during an 8-week, acute-treatment phase demonstrated a benefit of such maintenance treatment [see Clinical Studies (14.1)]. Nevertheless, the physician who elects to use escitalopram tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.2 Generalized Anxiety Disorder

Initial Treatment Adults The recommended starting dose of escitalopram tablets is 10 mg once daily. If the dose is increased to 20 mg, this should occur after a minimum of one week. Maintenance Treatment Generalized anxiety disorder is recognized as a chronic condition. The efficacy of escitalopram tablets in the treatment of GAD beyond 8 weeks has not been systematically studied. The physician who elects to use escitalopram tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

2.3 Special Populations

10 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment.No dosage adjustment is necessary for patients with mild or moderate renal impairment. Escitalopram tablets should be used with caution in patients with severe renal impairment.

2.4 Discontinuation of Treatment with Escitalopram Tablets

Symptoms associated with discontinuation of escitalopram tablets and other SSRIs and SNRIs have been reported [see Warnings and Precautions (5.3)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

2.5 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with escitalopram tablets. Conversely, at least 14 days should be allowed after stopping escitalopram tablets before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.6 Use of Escitalopram Tablets with Other MAOIs such as Linezolid or Methylene Blue

Do not start escitalopram tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)]. In some cases, a patient already receiving escitalopram tablets therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, escitalopram tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with escitalopram tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with escitalopram tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].
Duloxetine

Duloxetine

Swallow duloxetine delayed-release capsules whole. Do not chew or crush. Do not open the capsule and sprinkle its contents on food or mix with liquids. All of these might affect the enteric coating. Duloxetine delayed-release capsules can be given without regard to meals. If a dose of duloxetine delayed-release capsules is missed, take the missed dose as soon as it is remembered. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular time. Do not take two doses of duloxetine delayed-release capsules at the same time.

2.1 Dosage for Treatment of Major Depressive Disorder

Administer duloxetine delayed-release capsules at a total dose of 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily). For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer any additional benefits. The safety of doses above 120 mg/day has not been adequately evaluated. Periodically reassess to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.1)].

2.2 Dosage for Treatment of Generalized Anxiety Disorder

Adults — For most patients, initiate duloxetine delayed-release capsules 60 mg once daily. For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg once daily dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit. Nevertheless, if a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The safety of doses above 120 mg once daily has not been adequately evaluated. Periodically reassess to determine the continued need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2)].

Pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.'s duloxetine delayed-release capsules. However, due to Eli Lilly and Company, Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.3 Dosage for Treatment of Diabetic Peripheral Neuropathic Pain

Administer duloxetine delayed-release capsules 60 mg once daily. There is no evidence that doses higher than 60 mg confer additional significant benefit and the higher dose is clearly less well tolerated [see Clinical Studies (14.3)]. For patients for whom tolerability is a concern, a lower starting dose may be considered.

Since diabetes is frequently complicated by renal disease, consider a lower starting dose and gradual increase in dose for patients with renal impairment [see Dosage and Administration (2.6), Use in Specific Populations (8.10), and Clinical Pharmacology (12.3)].

2.5 Dosage for Treatment of Chronic Musculoskeletal Pain

Administer duloxetine delayed-release capsules 60 mg once daily. Begin treatment at 30 mg for one week, to allow patients to adjust to the medication before increasing to 60 mg once daily. There is no evidence that higher doses confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions [see Clinical Studies (14.5)].

2.6 Dosing in Special Populations

Hepatic Impairment — Avoid use in patients with chronic liver disease or cirrhosis [see Warnings and Precautions (5.14) and Use in Specific Populations (8.9)].

Severe Renal Impairment — Avoid use in patients with severe renal impairment, GFR <30 mL/min [see Warnings and Precautions (5.14)and Use in Specific Populations (8.10)].

2.7 Discontinuing Duloxetine Delayed-Release Capsules

Adverse reactions after discontinuation of duloxetine delayed-release capsules, after abrupt or tapered discontinuation, include: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see Warnings and Precautions (5.7)].

2.8 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with duloxetine delayed-release capsules. Conversely, at least 5 days should be allowed after stopping duloxetine delayed-release capsules before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4)].

2.9 Use of Duloxetine Delayed-Release Capsules with Other MAOIs such as Linezolid or Methylene Blue

Do not start duloxetine delayed-release capsules in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4)].

In some cases, a patient already receiving duloxetine delayed-release capsules therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, duloxetine delayed-release capsules should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with duloxetine delayed-release capsules may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.4)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with duloxetine delayed-release capsules is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.4)].
Escitalopram Oxalate So...

Escitalopram Oxalate Solution

Escitalopram oral solution should be administered once daily, in the morning or evening, with or without food.

2.1 Major Depressive Disorder

Initial Treatment Adolescents The recommended dose of escitalopram oral solution is 10 mg once daily. A flexible-dose trial of escitalopram oral solution (10 to 20 mg/day) demonstrated the effectiveness of escitalopram oral solution [see Clinical Studies (14.1)]. If the dose is increased to 20 mg, this should occur after a minimum of three weeks. Adults The recommended dose of escitalopram oral solution is 10 mg once daily. A fixed-dose trial of escitalopram oral solution demonstrated the effectiveness of both 10 mg and 20 mg of escitalopram oral solution, but failed to demonstrate a greater benefit of 20 mg over 10 mg [see Clinical Studies (14.1)]. If the dose is increased to 20 mg, this should occur after a minimum of one week. Maintenance Treatment It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of continuing escitalopram oral solution 10 or 20 mg/day in adults patients with major depressive disorder who responded while taking escitalopram oral solution during an 8-week, acute-treatment phase demonstrated a benefit of such maintenance treatment [see Clinical Studies (14.1)]. Nevertheless, the physician who elects to use escitalopram oral solution for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.2 Generalized Anxiety Disorder

Initial Treatment Adults The recommended starting dose of escitalopram oral solution is 10 mg once daily. If the dose is increased to 20 mg, this should occur after a minimum of one week. Maintenance Treatment Generalized anxiety disorder is recognized as a chronic condition. The efficacy of escitalopram oral solution in the treatment of GAD beyond 8 weeks has not been systematically studied. The physician who elects to use escitalopram oral solution for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

2.3 Special Populations

10 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment.No dosage adjustment is necessary for patients with mild or moderate renal impairment. Escitalopram oral solution should be used with caution in patients with severe renal impairment.

2.4 Discontinuation of Treatment with Escitalopram Oral Solution

Symptoms associated with discontinuation of escitalopram oral solution and other SSRIs and SNRIs have been reported [see Warnings and Precautions (5.3)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

2.5 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with escitalopram oral solution. Conversely, at least 14 days should be allowed after stopping escitalopram oral solution before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.6 Use of Escitalopram Oral Solution with Other MAOIs such as Linezolid or Methylene Blue

Do not start escitalopram oral solution in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)].

In some cases, a patient already receiving escitalopram oral solution therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, escitalopram oral solution should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with escitalopram oral solution may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with escitalopram oral solution is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].
Mirtazapine

Mirtazapine

Initial Treatment The recommended starting dose for mirtazapine orally disintegrating tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine tablets in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15 mg dose may benefit from dose increases up to a maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.Administration of Mirtazapine Orally Disintegrating Tablets Patients should be instructed to open tablet blister pack with dry hands and place the tablet on the tongue. The tablet should be used immediately after removal from its blister ; once removed, it cannot be stored. Mirtazapine Orally Disintegrating Tablets will disintegrate rapidly on the tongue and can be swallowed with saliva. No water is needed for taking the tablet. Patients should not attempt to split the tablet.Elderly and Patients with Renal or Hepatic Impairment The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY). Maintenance/Extended Treatment It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with mirtazapine orally disintegrating tablets. Conversely, at least 14 days should be allowed after stopping mirtazapine orally disintegrating tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).Use of Mirtazapine Orally Disintegrating Tablets With Other MAOIs, Such as Linezolid or Methylene Blue Do not start mirtazapine orally disintegrating tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving therapy with mirtazapine orally disintegrating tablets may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, mirtazapine orally disintegrating tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with mirtazapine orally disintegrating tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with mirtazapine orally disintegrating tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS). Discontinuation of Mirtazapine Treatment Symptoms associated with the discontinuation or dose reduction of mirtazapine orally disintegrating tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS). Information for Patients Patients should be advised that taking mirtazapine orally disintegrating tablets can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle-closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.
Mirtazapine

Mirtazapine

Initial Treatment

The recommended starting dose for mirtazapine tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15 mg dose may benefit from dose increases up to a maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.

Elderly and Patients with Renal or Hepatic Impairment

The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY).

Maintenance/Extended Treatment

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with mirtazapine tablets. Conversely, at least 14 days should be allowed after stopping mirtazapine tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Mirtazapine Tablets With Other MAOIs, Such as Linezolid or Methylene Blue

Do not start mirtazapine tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving therapy with mirtazapine tablets may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, mirtazapine tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with mirtazapine tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with mirtazapine tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Discontinuation of Mirtazapine Tablets Treatment

Symptoms associated with the discontinuation or dose reduction of mirtazapine tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS).

Information for Patients

Patients should be advised that taking mirtazapine tablets can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle-closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.
Hydrocodone Bitartrate ...

Hydrocodone Bitartrate And Acetaminophen

2.1 Asthma

Montelukast sodium tablets should be taken once daily in the evening. The following dose is recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.Safety and effectiveness in pediatric patients less than 12 months of age with asthma have not been established.There have been no clinical trials in patients with asthma to evaluate the relative efficacy of morning versus evening dosing. The pharmacokinetics of montelukast are similar whether dosed in the morning or evening. Efficacy has been demonstrated for asthma when montelukast was administered in the evening without regard to time of food ingestion.

2.2 Exercise-Induced Bronchoconstriction (EIB) in Patients 15 Years of Age and Older

For prevention of EIB, a single 10 mg dose of montelukast sodium tablets should be taken at least 2 hours before exercise. An additional dose of montelukast sodium tablets should not be taken within 24 hours of a previous dose. Patients already taking montelukast sodium tablets daily for another indication (including chronic asthma) should not take an additional dose to prevent EIB. All patients should have available for rescue a short-acting β-agonist. Safety and effectiveness in patients younger than 15 years of age have not been established. Daily administration of montelukast sodium tablets for the chronic treatment of asthma has not been established to prevent acute episodes of EIB.

Pediatric use information for patients ages 6 to 14 years of age for acute prevention of exercise-induced bronchoconstriction (EIB) is approved for Merck Sharp & Dohme Corp’s montelukast tablet products. However, due to Merck Sharp & Dohme Corp’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.3 Allergic Rhinitis

For allergic rhinitis, montelukast sodium tablets should be taken once daily. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion. The time of administration may be individualized to suit patient needs.The following dose for the treatment of symptoms of seasonal allergic rhinitis is recommended:For adults and adolescents 15 years of age and older: one 10 mg tablet.Safety and effectiveness in pediatric patients younger than 2 years of age with seasonal allergic rhinitis have not been established.The following dose for the treatment of symptoms of perennial allergic rhinitis is recommended: For adults and adolescents 15 years of age and older: one 10 mg tablet.Safety and effectiveness in pediatric patients younger than 6 months of age with perennial allergic rhinitis have not been established.

2.4 Asthma and Allergic Rhinitis

Patients with both asthma and allergic rhinitis should take only one montelukast sodium tablet dose daily in the evening.
Ranitidine

Ranitidine

Active Duodenal Ulcer

The current recommended adult oral dosage of ranitidine oral solution for duodenal ulcer is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice daily. An alternative dosage of 300 mg or 20 mL of oral solution (4 teaspoonfuls of oral solution equivalent to 300 mg of ranitidine) once daily after the evening meal or at bedtime can be used for patients in whom dosing convenience is important. The advantages of one treatment regimen compared to the other in a particular patient population have yet to be demonstrated (see Clinical Trials: Active Duodenal Ulcer). Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in U.S. studies, and several foreign trials have shown that 100 mg twice daily is as effective as the 150 mg dose.Antacid should be given as needed for relief of pain (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Maintenance of Healing of Duodenal Ulcers

The current recommended adult oral dosage is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) at bedtime.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome)

The current recommended adult oral dosage is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice daily. In some patients it may be necessary to administer ranitidine 150 mg doses more frequently. Dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. Dosages up to 6 g/day have been employed in patients with severe disease.

Benign Gastric Ulcer

The current recommended adult oral dosage is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice daily.

Maintenance of Healing of Gastric Ulcers

The current recommended adult oral dosage is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) at bedtime.

GERD

The current recommended adult oral dosage is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice daily.

Erosive Esophagitis

The current recommended adult oral dosage is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) 4 times daily.

Maintenance of Healing of Erosive Esophagitis

The current recommended adult oral dosage is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice daily.

Pediatric Use

The safety and effectiveness of ranitidine have been established in the age-group of 1 month to 16 years. There is insufficient information about the pharmacokinetics of ranitidine in neonatal patients (less than 1 month of age) to make dosing recommendations.The following 3 subsections provide dosing information for each of the pediatric indications.

Treatment of Duodenal and Gastric Ulcers

The recommended oral dose for the treatment of active duodenal and gastric ulcers is 2 to 4 mg/kg twice daily to a maximum of 300 mg/day. This recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients.

Maintenance of Healing of Duodenal and Gastric Ulcers

The recommended oral dose for the maintenance of healing of duodenal and gastric ulcers is 2 to 4 mg/kg once daily to a maximum of 150 mg/day. This recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients.

Treatment of GERD and Erosive Esophagitis

Although limited data exist for these conditions in pediatric patients, published literature supports a dosage of 5 to 10 mg/kg/day, usually given as 2 divided doses.

Dosage Adjustment for Patients With Impaired Renal Function

On the basis of experience with a group of subjects with severely impaired renal function treated with ranitidine, the recommended dosage in patients with a creatinine clearance <50 mL/min is 150 mg or 10 mL of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) every 24 hours. Should the patient's condition require, the frequency of dosing may be increased to every 12 hours or even further with caution. Hemodialysis reduces the level of circulating ranitidine. Ideally, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.Elderly patients are more likely to have decreased renal function, therefore caution should be exercised in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and PRECAUTIONS: Geriatric Use).
Tamsulosin Hydrochlorid...

Tamsulosin Hydrochloride

Tamsulosin hydrochloride capsules 0.4 mg once daily is recommended as the dose for the treatment of the signs and symptoms of BPH. It should be administered approximately one-half hour following the same meal each day. Tamsulosin hydrochloride capsules should not be crushed, chewed or opened.

For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing, the dose of tamsulosin hydrochloride capsules can be increased to 0.8 mg once daily. Tamsulosin hydrochloride capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [see Warnings and Precautions (5.2)].

If tamsulosin hydrochloride capsules

administration is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose, therapy should be started again with the 0.4 mg once-daily dose.
Stavudine

Stavudine

The interval between doses of stavudine for oral solution should be 12 hours. Stavudine for oral solution may be taken with or without food.

2.1 Recommended Adult Dosage

The recommended adult dosage is based on body weight as follows:
For patients weighing less than 60 kg: 30 mg every 12 hours. For patients weighing at least 60 kg: 40 mg every 12 hours.
2.2 Recommended Pediatric Dosage
For newborns from birth to 13 days old: 0.5 mg/kg given every 12 hours. For pediatric patients at least 14 days old and weighing less than 30 kg: 1 mg/kg given every 12 hours. For pediatric patients weighing at least 30 kg: use the recommended adult dosage.
2.3 Dosage Adjustment

Renal Impairment Adult Patients: Stavudine for oral solution may be administered to adult patients with impaired renal function with an adjustment in dosage as shown in Table 1.
Table 1: Recommended Dosage Adjustment for Adult Patients with Renal Impairment Creatinine Clearance(mL/min) Recommended Stavudine for Oral Solution Doseby Patient Weight at least 60 kg less than 60 kg * Administered after the completion of hemodialysis on dialysis days and at the same time of day on non-dialysis days. greater than 50 40 mg every 12 hours 30 mg every 12 hours 26–50 20 mg every 12 hours 15 mg every 12 hours 10–25 20 mg every 24 hours 15 mg every 24 hours Hemodialysis 20 mg every 24 hours* 15 mg every 24 hours*
Pediatric Patients: Since urinary excretion is also a major route of elimination of stavudine in pediatric patients, the clearance of stavudine may be altered in children with renal impairment. There are insufficient data to recommend a specific dose adjustment of stavudine for oral solution in this patient population.

2.4 Method of Preparation for Oral Solution

Prior to dispensing, the pharmacist must constitute the dry powder with purified water to a concentration of 1 mg stavudine per mL of solution, as follows:
Add 193 mL of purified water to the container. Shake container vigorously until the powder dissolves completely. Constitution in this way produces 200 mL (deliverable volume) of 1 mg/mL stavudine solution. The solution may appear slightly hazy. Dispense solution in original container with measuring cup provided. Instruct patient to shake the container vigorously prior to measuring each dose and to store the tightly closed container in a refrigerator, 2° to 8°C (36° to 46°F). Discard any unused portion after 30 days.
Clarithromycin

Clarithromycin

Clarithromycin tablets may be given with or without food.Clarithromycin may be administered without dosage adjustment in the presence of hepatic impairment if there is normal renal function. In patients with severe renal impairment (CLCR < 30 mL/min), the dose of clarithromycin should be reduced by 50%. However, when patients with moderate or severe renal impairment are taking clarithromycin concomitantly with atazanavir or ritonavir, the dose of clarithromycin should be reduced by 50% or 75% for patients with CLCR of 30 to 60 mL/min or < 30 mL/min, respectively.
ADULT DOSAGE GUIDELINES Clarithromycin Tablets Infection Dosage(q 12 h) Duration(Days) Pharyngitis/Tonsillitis due to S. pyogenes 250 mg 10 Acute maxillary sinusitis due to 500 mg 14 H. influenzae M. catarrhalis S. pneumoniae Acute exacerbation of chronic bronchitis due to H. influenzae 500 mg 7 to 14 H. parainfluenzae 500 mg 7 M. catarrhalis 250 mg 7 to 14 S. pneumoniae 250 mg 7 to 14 Community-Acquired Pneumonia due to H. influenzae 250 mg 7 H. parainfluenzae - - M. catarrhalis - - S. pneumoniae 250 mg 7 to 14 C. pneumoniae 250 mg 7 to 14 M. pneumoniae 250 mg 7 to 14 Uncomplicated skin and skin structure 250 mg 7 to 14 S. aureus S. pyogenes
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple therapy: clarithromycin/lansoprazole/amoxicillinThe recommended adult dose is 500 mg clarithromycin, 30 mg lansoprazole, and 1 gram amoxicillin, all given twice daily (q 12 h) for 10 or 14 days (see INDICATIONS AND USAGE and CLINICAL STUDIES sections).Triple therapy: clarithromycin/omeprazole/amoxicillinThe recommended adult dose is 500 mg clarithromycin, 20 mg omeprazole, and 1 gram amoxicillin, all given twice daily (q 12 h) for 10 days (see INDICATIONS AND USAGE and CLINICAL STUDIES sections). In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.Dual therapy: clarithromycin/omeprazoleThe recommended adult dose is 500 mg clarithromycin given three times daily (q 8 h) and 40 mg omeprazole given once daily (qAM) for 14 days (see INDICATIONS AND USAGE and CLINICAL STUDIES sections). An additional 14 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.Dual therapy: clarithromycin/ranitidine bismuth citrateThe recommended adult dose is 500 mg clarithromycin given twice daily (q 12 h) or three times daily (q 8 h) and 400 mg ranitidine bismuth citrate given twice daily (q 12 h) for 14 days. An additional 14 days of 400 mg twice daily is recommended for ulcer healing and symptom relief. Clarithromycin and ranitidine bismuth citrate combination therapy is not recommended in patients with creatinine clearance less than 25 mL/min (see INDICATIONS AND USAGE and CLINICAL STUDIES sections).ChildrenThe usual recommended daily dosage is 15 mg/kg/day divided q 12 h for 10 days.
PEDIATRIC DOSAGE GUIDELINES Based on Body Weight Dosing Calculated on 7.5 mg/kg q 12 h Weight Dose Kg lbs (q 12 h) 9 20 62.5 mg 17 37 125 mg 25 55 187.5 mg 33 73 250 mg
Mycobacterial Infections

ProphylaxisThe recommended dose of clarithromycin for the prevention of disseminated Mycobacterium avium disease is 500 mg b.i.d. In children, the recommended dose is 7.5 mg/kg b.i.d. up to 500 mg b.i.d. No studies of clarithromycin for MAC prophylaxis have been performed in pediatric populations and the doses recommended for prophylaxis are derived from MAC treatment studies in children. Dosing recommendations for children are in the table above.TreatmentClarithromycin is recommended as the primary agent for the treatment of disseminated infection due to Mycobacterium avium complex. Clarithromycin should be used in combination with other antimycobacterial drugs that have shown in vitro activity against MAC or clinical benefit in MAC treatment (see CLINICAL STUDIES). The recommended dose for mycobacterial infections in adults is 500 mg b.i.d. In children, the recommended dose is 7.5 mg/kg b.i.d. up to 500 mg b.i.d. Dosing recommendations for children are in the table above.Clarithromycin therapy should continue if clinical response is observed. Clarithromycin can be discontinued when the patient is considered at low risk of disseminated infection.
Cefdinir

Cefdinir

(see INDICATIONS AND USAGE for Indicated Pathogens)The recommended dosage and duration of treatment for infections in adults and adolescents are described in the following chart; the total daily dose for all infections is 600 mg. Once-daily dosing for 10 days is as effective as BID dosing. Once-daily dosing has not been studied in pneumonia or skin infections; therefore, cefdinir capsules should be administered twice daily in these infections. Cefdinir capsules may be taken without regard to meals.
Adults and Adolescents (Age 13 Years and Older) Type of Infection Dosage Duration Community-Acquired Pneumonia 300 mg q12h 10 days Acute Exacerbations of Chronic Bronchitis 300 mg q12h or600 mg q24h 5 to 10 days 10 days Acute Maxillary Sinusitis 300 mg q12h or600 mg q24h 10 days10 days Pharyngitis/Tonsillitis 300 mg q12h or600 mg q24h 5 to 10 days 10 days Uncomplicated Skin and Skin Structure Infections 300 mg q12h 10 days
Patients With Renal Insufficiency

For adult patients with creatinine clearance <30 mL/min, the dose of cefdinir should be 300 mg given once daily.Creatinine clearance is difficult to measure in outpatients. However, the following formula may be used to estimate creatinine clearance (CLcr) in adult patients. For estimates to be valid, serum creatinine levels should reflect steady-state levels of renal function.Males: CLcr = (weight) (140 – age) (72) (serum creatinine)Females: CLcr = 0.85 x above valuewhere creatinine clearance is in mL/min, age is in years, weight is in kilograms, and serum creatinine is in mg/dL(3).The following formula may be used to estimate creatinine clearance in pediatric patients:CLcr = K x body length or height serum creatinineWhere K=0.55 for pediatric patients older than 1 year(4) and 0.45 for infants (up to 1 year)(5).In the above equation, creatinine clearance is in mL/min/1.73 m2, body length or height is in centimeters, and serum creatinine is in mg/dL.For pediatric patients with a creatinine clearance of <30 mL/min/1.73 m2, the dose of cefdinir should be 7 mg/kg (up to 300 mg) given once daily.

Patients on Hemodialysis

Hemodialysis removes cefdinir from the body. In patients maintained on chronic hemodialysis, the recommended initial dosage regimen is a 300 mg or 7 mg/kg dose every other day. At the conclusion of each hemodialysis session, 300 mg (or 7 mg/kg) should be given. Subsequent doses (300 mg or 7 mg/kg) are then administered every other day.
Levetiracetam

Levetiracetam

2.1 Important Administration Instructions

Levetiracetam tablets are given orally with or without food. The levetiracetam dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.Prescribe the oral solution for pediatric patients with body weight ≤ 20 kg. Prescribe the  oral solution or tablets for pediatric patients with body weight above 20 kg.When using the oral solution in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).Levetiracetam tablets should be swallowed whole. Levetiracetam tablets should not be chewed or crushed.

2.2 Dosing for Partial Onset Seizures

Adults 16 Years and Older

Initiate treatment with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients

1 Month to < 6 Months

Initiate treatment with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg (21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. The effectiveness of lower doses has not been studied.

6 Months to <4 Years:

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a patient cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group.

4 Years to < 16 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3000 mg/day.

For levetiracetam tablet dosing in pediatric patients weighing 20 to 40 kg, initiate treatment with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). Increase the daily dose every 2 weeks by increments of 500 mg to a maximum recommended daily dose of 1500 mg (750 mg twice daily).

For levetiracetam tablet dosing in pediatric patients weighing more than 40 kg, initiate treatment with a daily dose of 1000 mg/day given as twice daily dosing (500 mg twice daily). Increase the daily dose every 2 weeks by increments of 1000 mg/day to a maximum recommended daily dose of 3000 mg (1500 mg twice daily).

Levetiracetam Oral Solution Weight-Based Dosing Calculation For Pediatric Patients

The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients:

                                                         Daily dose (mg/kg/day) x patient weight (kg)

Total daily dose (mL/day) = -------------------------------------------------------------

                                                                100 mg/mL

2.3 Dosing for Myoclonic Seizures in Patients 12 Years of Age and Older with Juvenile Myoclonic Epilepsy

Initiate treatment with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase the dosage by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.

2.4 Dosing for Primary Generalized Tonic-Clonic Seizures

Adults 16 Years and Older Initiate treatment with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase dosage by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied. Pediatric Patients Ages 6 to <16 YearsInitiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution [see Dosage and Administration (2.1)]. Only whole tablets should be administered.

2.5 Dosage Adjustments in Adult Patients with Renal Impairment

Levetiracetam tablet dosing must be individualized according to the patient’s renal function status. Recommended dosage adjustments for adults are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this an estimate of the patient’s creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:                     [140-age (years)] x weight (kg)CLcr = ----------------------------------------------(x 0.85 for female patients)                     72 x serum creatinine (mg/dL)

Then CLcr is adjusted for body surface area (BSA) as follows:                                                   CLcr (mL/min)CLcr (mL/min/1.73 m2) = -------------------------- x 1.73                                                   BSA subject (m2)
Table 1: Dosing Adjustment Regimen for Adult Patients with Renal Impairment Group Creatinine Clearance (mL/min/1.73 m2) Dosage (mg) Frequency 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended.    Normal > 80 500 to 1,500 Every 12 hours    Mild 50 – 80 500 to 1,000 Every 12 hours    Moderate 30 – 50 250 to 750 Every 12 hours    Severe < 30 250 to 500 Every 12 hours    ESRD patients using dialysis ---- 500 to 1,0001 Every 24 hours1
Dextroamphetamine Sacch...

Dextroamphetamine Saccharate

2.1 Major Depressive Disorder

Initial Treatment Adult — Initiate fluoxetine capsules 20 mg/day orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon). The maximum fluoxetine dose should not exceed 80 mg/day.In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 to 80 mg/day. Studies comparing fluoxetine 20, 40, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in Major Depressive Disorder in most cases [see Clinical Studies (14.1)]. Pediatric (children and adolescents) — Initiate fluoxetine capsules 10 or 20 mg/day. After 1 week at 10 mg/day, increase the dose to 20 mg/day. However, due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day. Consider a dose increase to 20 mg/day after several weeks if insufficient clinical improvement is observed. In the short-term (8 to 9 week) controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Major Depressive Disorder, patients were administered fluoxetine doses of 10 to 20 mg/day [see Clinical Studies (14.1)]. All patients — As with other drugs effective in the treatment of Major Depressive Disorder, the full effect may be delayed until 4 weeks of treatment or longer.Periodically reassess to determine the need for maintenance treatment. Switching Patients to a Tricyclic Antidepressant (TCA) — Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Drug Interactions (7.7)].

2.2 Obsessive Compulsive Disorder

Initial Treatment Adult — Initiate fluoxetine capsules 20 mg/day, orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon). A dose range of 20 to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose should not exceed 80 mg/day.In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20, 40, or 60 mg of fluoxetine or placebo [see Clinical Studies (14.2)]. In one of these studies, no dose-response relationship for effectiveness was demonstrated. Pediatric (children and adolescents) — In adolescents and higher weight children, initiate treatment with a dose of 10 mg/day. After 2 weeks, increase the dose to 20 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 60 mg/day is recommended.In lower weight children, initiate treatment with a dose of 10 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 30 mg/day is recommended. Experience with daily doses greater than 20 mg is very minimal, and there is no experience with doses greater than 60 mg.In the controlled clinical trial of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.2)].Periodically reassess to determine the need for treatment.

2.3 Bulimia Nervosa

Initial Treatment — Administer fluoxetine capsules 60 mg/day in the morning. For some patients it may be advisable to titrate up to this target dose over several days. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with bulimia. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Bulimia Nervosa, patients were administered fixed daily fluoxetine doses of 20 or 60 mg, or placebo [see Clinical Studies (14.3)]. Only the 60 mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting.Periodically reassess to determine the need for maintenance treatment.

2.4 Panic Disorder

Initial Treatment — Initiate treatment with fluoxetine capsules 10 mg/day. After one week, increase the dose to 20 mg/day. Consider a dose increase after several weeks if no clinical improvement is observed. Fluoxetine doses above 60 mg/day have not been systematically evaluated in patients with Panic Disorder. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Panic Disorder, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.4)]. The most frequently administered dose in the 2 flexible-dose clinical trials was 20 mg/day.Periodically reassess to determine the need for continued treatment.

2.5 Fluoxetine Capsules and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder

When using fluoxetine capsules and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.

Adult — Administer fluoxetine in combination with oral olanzapine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Make dosage adjustments, if indicated, according to efficacy and tolerability within dose ranges of fluoxetine 20 to 50 mg and oral olanzapine 5 to 12.5 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination with a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg. Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. Periodically re-examine the need for continued pharmacotherapy. Information for pediatric patients (10 to 17 years) is approved for Eli Lilly and Company’s Fluoxetine Capsules. However due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine capsules and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
Table 1: Approximate Dose Correspondence Between Symbyax1 and the Combination of Fluoxetine and Olanzapine For Symbyax (mg/day) Use in Combination Olanzapine (mg/day) Fluoxetine (mg/day) 1 Symbyax (olanzapine/fluoxetine hydrochloride) is a fixed-dose combination of fluoxetine and olanzapine. 3 mg olanzapine/25 mg fluoxetine 2.5 20 6 mg olanzapine/25 mg fluoxetine 5 20 12 mg olanzapine/25 mg fluoxetine 10+2.5 20 6 mg olanzapine/50 mg fluoxetine 5 40+10 12 mg olanzapine/50 mg fluoxetine 10+2.5 40+10
Fluoxetine capsules monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder.

2.7 Dosing in Specific Populations

Treatment of Pregnant Women — When treating pregnant women with fluoxetine capsules, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding [see Use in Specific Populations (8.1)]. Geriatric — Consider a lower or less frequent dosage for the elderly [see Use in Specific Populations (8.5)]. Hepatic Impairment — As with many other medications, use a lower or less frequent dosage in patients with hepatic impairment [see Clinical Pharmacology (12.4) and Use in Specific Populations (8.6)]. Concomitant Illness — Patients with concurrent disease or on multiple concomitant medications may require dosage adjustments [see Clinical Pharmacology (12.4) and Warnings and Precautions (5.12)]. Fluoxetine Capsules and Olanzapine in Combination — Use a starting dose of oral olanzapine 2.5 to 5 mg with fluoxetine 20 mg for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine or fluoxetine in combination (female gender, geriatric age, non-smoking status), or those patients who may be pharmacodynamically sensitive to olanzapine. Titrate slowly and adjust dosage as needed in patients who exhibit a combination of factors that may slow metabolism. Fluoxetine capsules and olanzapine in combination have not been systematically studied in patients over 65 years of age or in patients less than 10 years of age [see Warnings and Precautions (5.16) and Drug Interactions (7.7)].

2.8 Discontinuation of Treatment

Symptoms associated with discontinuation of fluoxetine, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5.15)].

2.9 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with fluoxetine capsules. Conversely, at least 5 weeks should be allowed after stopping fluoxetine capsules before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.10 Use of Fluoxetine Capsules with Other MAOIs such as Linezolid or Methylene Blue

Do not start fluoxetine capsules in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)]. In some cases, a patient already receiving fluoxetine capsules therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, fluoxetine capsules should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with fluoxetine capsules may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with fluoxetine capsules is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].
Tramadol Hydrochloride

Tramadol Hydrochloride

Adults (17 years of age and over) For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, the tolerability of tramadol hydrochloride tablets can be improved by initiating therapy with a titration regimen: The total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.). After titration, tramadol hydrochloride tablets 50 mg to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day.For the subset of patients for whom rapid onset of analgesic effect is required and for whom the benefits outweigh the risk of discontinuation due to adverse events associated with higher initial doses, tramadol hydrochloride tablets 50 mg to 100 mg can be administered as needed for pain relief every four to six hours, not to exceed 400 mg per day. Individualization of Dose Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Studies with tramadol in adults have shown that starting at the lowest possible dose and titrating upward will result in fewer discontinuations and increased tolerability.
In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride tablets be increased to 12 hours, with a maximum daily dose of 200 mg. Since only 7% of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis. The recommended dose for adult patients with cirrhosis is 50 mg every 12 hours. In general, dose selection for an elderly patient over 65 years old should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. For elderly patients over 75 years old, total dose should not exceed 300 mg/day.
Sertraline Hydrochlorid...

Sertraline Hydrochloride Solution

Initial Treatment

Dosage for Adults

Major Depressive Disorder and Obsessive-Compulsive Disorder

Sertraline hydrochloride treatment should be administered at a dose of 50 mg once daily. Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder Sertraline hydrochloride treatment should be initiated with a dose of 25 mg once daily. After one week, the dose should be increased to 50 mg once daily.While a relationship between dose and effect has not been established for major depressive disorder, OCD, panic disorder, PTSD or social anxiety disorder, patients were dosed in a range of 50 to 200 mg/day in the clinical trials demonstrating the effectiveness of sertraline hydrochloride for the treatment of these indications. Consequently, a dose of 50 mg, administered once daily, is recommended as the initial therapeutic dose. Patients not responding to a 50 mg dose may benefit from dose increases up to a maximum of 200 mg/day. Given the 24 hour elimination half-life of sertraline hydrochloride, dose changes should not occur at intervals of less than 1 week. Premenstrual Dysphoric Disorder Sertraline hydrochloride treatment should be initiated with a dose of 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment.While a relationship between dose and effect has not been established for PMDD, patients were dosed in the range of 50 to 150 mg/day with dose increases at the onset of each new menstrual cycle (see Clinical Trials under CLINICAL PHARMACOLOGY). Patients not responding to a 50 mg/day dose may benefit from dose increases (at 50 mg increments/menstrual cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100 mg/day dose has been established with luteal phase dosing, a 50 mg/day titration step for three days should be utilized at the beginning of each luteal phase dosing period.Sertraline hydrochloride should be administered once daily, either in the morning or evening.Dosage for Pediatric Population (Children and Adolescents) Obsessive-Compulsive DisorderSertraline hydrochloride treatment should be initiated with a dose of 25 mg once daily in children (ages 6 to 12) and at a dose of 50 mg once daily in adolescents (ages 13 to 17).While a relationship between dose and effect has not been established for OCD, patients were dosed in a range of 25 to 200 mg/day in the clinical trials demonstrating the effectiveness of sertraline hydrochloride for pediatric patients (6 to 17 years) with OCD. Patients not responding to an initial dose of 25 or 50 mg/day may benefit from dose increases up to a maximum of 200 mg/day. For children with OCD, their generally lower body weights compared to adults should be taken into consideration in advancing the dose, in order to avoid excess dosing. Given the 24 hour elimination half-life of sertraline hydrochloride, dose changes should not occur at intervals of less than 1 week. Sertraline hydrochloride should be administered once daily, either in the morning or evening.

Maintenance/Continuation/Extended Treatment

Major Depressive Disorder

It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy beyond response to the acute episode. Systematic evaluation of sertraline hydrochloride has demonstrated that its antidepressant efficacy is maintained for periods of up to 44 weeks following 8 weeks of initial treatment at a dose of 50 to 200 mg/day (mean dose of 70 mg/day) (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.Posttraumatic Stress DisorderIt is generally agreed that PTSD requires several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline hydrochloride has demonstrated that its efficacy in PTSD is maintained for periods of up to 28 weeks following 24 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.Social Anxiety DisorderSocial anxiety disorder is a chronic condition that may require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of sertraline hydrochloride has demonstrated that its efficacy in social anxiety disorder is maintained for periods of up to 24 weeks following 20 weeks of treatment at a dose of 50 to 200 mg/day (see Clinical Trials under CLINICAL PHARMACOLOGY). Dosage adjustments should be made to maintain patients on the lowest effective dose and patients should be periodically reassessed to determine the need for long-term treatment.Obsessive-Compulsive Disorder and Panic DisorderIt is generally agreed that OCD and Panic Disorder require several months or longer of sustained pharmacological therapy beyond response to initial treatment. Systematic evaluation of continuing sertraline hydrochloride for periods of up to 28 weeks in patients with OCD and Panic Disorder who have responded while taking sertraline hydrochloride during initial treatment phases of 24 to 52 weeks of treatment at a dose range of 50 to 200 mg/day has demonstrated a benefit of such maintenance treatment (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride needed for maintenance treatment is identical to the dose needed to achieve an initial response. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment.Premenstrual Dysphoric DisorderThe effectiveness of sertraline hydrochloride in long-term use, that is, for more than 3 menstrual cycles, has not been systematically evaluated in controlled trials. However, as women commonly report that symptoms worsen with age until relieved by the onset of menopause, it is reasonable to consider continuation of a responding patient. Dosage adjustments, which may include changes between dosage regimens (e.g., daily throughout the menstrual cycle versus during the luteal phase of the menstrual cycle), may be needed to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with sertraline hydrochloride. Conversely, at least 14 days should be allowed after stopping sertraline hydrochloride before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS). Use of Sertraline Hydrochloride With Other MAOIs Such as Linezolid or Methylene Blue Do not start sertraline hydrochloride in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).In some cases, a patient already receiving sertraline hydrochloride therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, sertraline hydrochloride should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with sertraline hydrochloride may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with sertraline hydrochloride is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Special Populations

Dosage for Hepatically Impaired Patients

The use of sertraline in patients with liver disease should be approached with caution. The effects of sertraline in patients with moderate and severe hepatic impairment have not been studied. If sertraline is administered to patients with liver impairment, a lower or less frequent dose should be used (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to sertraline hydrochloride and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with sertraline hydrochloride during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Discontinuation of Treatment with Sertraline Hydrochloride

Symptoms associated with discontinuation of sertraline hydrochloride and other SSRIs and SNRIs, have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

Sertraline Hydrochloride Oral solution

Sertraline hydrochloride oral solution contains 20 mg/mL of sertraline (as the hydrochloride) as the active ingredient and 12% alcohol. Sertraline hydrochloride oral solution must be diluted before use. Just before taking, use the dispensing syringe provided to remove the required amount of sertraline hydrochloride oral solution and mix with 4 oz (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY. Do not mix sertraline hydrochloride oral solution with anything other than the liquids listed. The dose should be taken immediately after mixing. Do not mix in advance. At times, a slight haze may appear after mixing; this is normal.Sertraline hydrochloride oral solution is contraindicated with ANTABUSE (disulfiram) due to the alcohol content of the concentrate.
Finasteride

Finasteride

Finasteride tablets may be administered with or without meals.The recommended dose of finasteride is one tablet (1 mg) taken once daily.In general, daily use for three months or more is necessary before benefit is observed. Continued use is recommended to sustain benefit, which should be re-evaluated periodically. Withdrawal of treatment leads to reversal of effect within 12 months.
Divalproex Sodium

Divalproex Sodium

Divalproex sodium extended-release tablets are an extended-release product intended for once-a-day oral administration. Divalproex sodium extended-release tablets should be swallowed whole and should not be crushed or chewed.

2.1 Mania

Divalproex sodium extended-release tablets are administered orally. The recommended initial dose is 25 mg/kg/day given once daily. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In a placebo-controlled clinical trial of acute mania or mixed type, patients were dosed to a clinical response with a trough plasma concentration between 85 and 125 mcg/mL. The maximum recommended dosage is 60 mg/kg/day. There is no body of evidence available from controlled trials to guide a clinician in the longer term management of a patient who improves during divalproex sodium extended-release tablets treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no data to support the benefits of divalproex sodium extended-release tablets in such longer-term treatment (i.e., beyond 3 weeks).

2.2 Epilepsy

Divalproex sodium extended-release tablets are administered orally, and must be swallowed whole. As divalproex sodium extended-release tablets dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions (7.2)]. Complex Partial Seizures For adults and children 10 years of age or older. Monotherapy (Initial Therapy) Divalproex sodium extended-release tablets have not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.Conversion to Monotherapy Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of divalproex sodium extended-release tablets therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.Adjunctive Therapy Divalproex sodium extended-release tablets may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to valproate, no adjustment of carbamazepine or phenytoin dosage was needed [see Clinical Studies (14.2)]. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see Drug Interactions (7)]. Simple and Complex Absence Seizures The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentration for most patients with absence seizures is considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see Clinical Pharmacology (12.3)]. As divalproex sodium extended-release tablets dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see Drug Interactions (7.2)]. Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.

2.3 Migraine

Divalproex sodium extended-release tablets are indicated for prophylaxis of migraine headaches in adults. The recommended starting dose is 500 mg once daily for 1 week, thereafter increasing to 1000 mg once daily. Although doses other than 1000 mg once daily of divalproex sodium extended-release tablets have not been evaluated in patients with migraine, the effective dose range of divalproex sodium delayed-release tablets in these patients is 500 to 1000 mg/day. As with other valproate products, doses of divalproex sodium extended-release tablets should be individualized and dose adjustment may be necessary. If a patient requires smaller dose adjustments than that available with divalproex sodium extended-release tablets, divalproex sodium delayed-release tablets should be used instead.

2.4 Conversion from Divalproex Sodium Delayed-Release Tablets to Divalproex Sodium Extended-Release Tablets

In adult patients and pediatric patients 10 years of age or older with epilepsy previously receiving divalproex sodium delayed-release tablets, divalproex sodium extended-release tablets should be administered once-daily using a dose 8 to 20% higher than the total daily dose of divalproex sodium delayed-release tablets (Table 1). For patients whose divalproex sodium delayed-release tablets total daily dose cannot be directly converted to divalproex sodium extended-release tablets, consideration may be given at the clinician’s discretion to increase the patient’s divalproex sodium delayed-release tablets total daily dose to the next higher dosage before converting to the appropriate total daily dose of divalproex sodium extended-release tablets.
Table 1. Dose Conversion * These total daily doses of divalproex sodium delayed-release tablets cannot be directly converted to an 8 to 20% higher total daily dose of divalproex sodium extended-release tablets because the required dosing strengths of divalproex sodium extended-release tablets are not available. Consideration may be given at the clinician's discretion to increase the patient’s divalproex sodium delayed-release tablets total daily dose to the next higher dosage before converting to the appropriate total daily dose of divalproex sodium extended-release tablets. Divalproex Sodium Delayed-Release Tablets Divalproex Sodium Extended-Release Tablets Total Daily Dose (mg) (mg) 500* to 625 750 750* to 875 1000 1000* to 1125 1250 1250 to 1375 1500 1500 to 1625 1750 1750 2000 1875 to 2000 2250 2125 to 2250 2500 2375 2750 2500 to 2750 3000 2875 3250 3000 to 3125 3500
There is insufficient data to allow a conversion factor recommendation for patients with divalproex sodium delayed-release tablets doses above 3125 mg/day. Plasma valproate Cmin concentrations for divalproex sodium extended-release tablets on average are equivalent to divalproex sodium delayed-release tablets, but may vary across patients after conversion. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL) [see Clinical Pharmacology (12.2)].

2.5 General Dosing Advice

Dosing in Elderly Patients Due to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Starting doses in the elderly lower than 250 mg can only be achieved by the use of divalproex sodium delayed-release tablets. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see Warnings and Precautions (5.14), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)]. Dose-Related Adverse Reactions The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see Warnings and Precautions (5.8)]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions. G.I. Irritation Patients who experience G.I. irritation may benefit from administration of the drug with food or by slowly building up the dose from an initial low level.Compliance Patients should be informed to take divalproex sodium extended-release tablets every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.
Zidovudine Syrup

Zidovudine Syrup

2.1 Adults-Treatment of HIV-1 Infection

Oral DosingThe recommended oral dose of zidovudine oral solution is 300 mg twice daily in combination with other antiretroviral agents.

2.2 Pediatric Patients (Aged 4 Weeks to Less than 18 Years)

Healthcare professionals should pay special attention to accurate calculation of the dose of zidovudine oral solution, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.Prescribers should calculate the appropriate dose of zidovudine oral solution for each child based on body weight (kg) and should not exceed the recommended adult dose.Before prescribing zidovudine capsules or tablets, children should be assessed for the ability to swallow capsules or tablets. If a child is unable to reliably swallow a zidovudine capsule or tablet, the zidovudine syrup (zidovudine oral solution, USP) formulation should be prescribed.The recommended oral dosage in pediatric patients 4 weeks to less than 18 years and weighing greater than or equal to 4 kg is provided in Table 1. Zidovudine oral solution should be used to provide accurate dosage when whole tablets or capsules are not appropriate.
Table 1: Recommended Pediatric Oral Dosage of Zidovudine Oral Solution Body Weight (kg) Total Daily Dose Dosage Regimen and Dose Twice Daily Three Times Daily 4 to <9 24 mg/kg/day 12 mg/kg 8 mg/kg ≥9 to <30 18 mg/kg/day 9 mg/kg 6 mg/kg ≥30 600 mg/day 300 mg 200 mg
Alternatively, dosing for zidovudine oral solution can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine oral solution is 480 mg per m2 per day in divided doses (240 mg per m2 twice daily or 160 mg per m2 three times daily). In some cases the dose calculated by mg per kg will not be the same as that calculated by BSA.

2.3 Prevention of Maternal-Fetal HIV-1 Transmission

The recommended dosage regimen for administration to pregnant women (greater than 14 weeks of pregnancy) and their neonates is: Maternal Dosing: 100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous zidovudine should be administered at 2 mg per kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg per kg per hour (total body weight) until clamping of the umbilical cord. Neonatal Dosing: Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously. See Table 2.
Table 2. Recommended Neonatal Dosages of Zidovudine Route Total Daily Dose Dose and Dosage Regimen Oral 8 mg/kg/day 2 mg/kg every 6 hours Intravenous 6 mg/kg/day 1.5 mg/kg infused over 30 minutes, every 6 hours
2.4 Patients With Severe Anemia and/or Neutropenia

Significant anemia (hemoglobin less than 7.5 g per dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells per mm3 or reduction greater than 50% from baseline) may require a dose interruption until evidence of marrow recovery is observed [see Warnings and Precautions (5.1)]. In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoetin level and patient tolerance.

2.5 Patients With Renal Impairment

In patients maintained on hemodialysis or peritoneal dialysis or with creatinine clearance (CrCl) by Cockcroft-Gault less than 15 mL per min, the recommended oral dosage is 100 mg every 6 to 8 hours [see Use in Specific Populations (8.6),Clinical Pharmacology (12.3)].

2.6 Patients With Hepatic Impairment

There are insufficient data to recommend dose adjustment of zidovudine oral solution in patients with impaired hepatic function or liver cirrhosis. Frequent monitoring of hematologic toxicities is advised [see Use in Specific Populations (8.7)].
Quinapril Hydrochloride...

Quinapril Hydrochloride And Hydrochlorothiazide

2.1 Hypertension

The recommended initial dose for patients not receiving a diuretic is 2.5 mg once a day. Adjust dose according to blood pressure response. The usual maintenance dosage range is 2.5 mg to 20 mg per day administered as a single dose or in two equally divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients, consider an increase in dosage or twice daily administration. If blood pressure is not controlled with ramipril capsules alone, a diuretic can be added.

2.3 Heart Failure Post-Myocardial Infarction

For the treatment of post-myocardial infarction patients who have shown signs of congestive heart failure, the recommended starting dose of ramipril capsules is 2.5 mg twice daily (5 mg per day). A patient who becomes hypotensive at this dose may be switched to 1.25 mg twice daily. After one week at the starting dose, increase dose (if tolerated) toward a target dose of 5 mg twice daily, with dosage increases being about 3 weeks apart.After the initial dose of ramipril capsules, observe the patient under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour. If possible, reduce the dose of any concomitant diuretic as this may diminish the likelihood of hypotension. The appearance of hypotension after the initial dose of ramipril capsules does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension [see Warnings and Precautions (5.5), Drug Interactions (7.1)].

2.4 General Dosing Information

Generally, swallow ramipril capsules whole. The ramipril capsule can also be opened and the contents sprinkled on a small amount (about 4 oz.) of applesauce or mixed in 4 oz. (120 mL) of water or apple juice. To be sure that ramipril is not lost when such a mixture is used, consume the mixture in its entirety. The described mixtures can be pre-prepared and stored for up to 24 hours at room temperature or up to 48 hours under refrigeration.Concomitant administration of ramipril capsules with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium [see Warnings and Precautions (5.8)].

2.5 Dosage Adjustment

Renal Impairment Establish baseline renal function in patients initiating ramipril capsules. Usual regimens of therapy with ramipril capsules may be followed in patients with estimated creatinine clearance >40 mL/min. However, in patients with worse impairment, 25% of the usual dose of ramipril is expected to produce full therapeutic levels of ramiprilat [see Use in Specific Populations (8.6)].Hypertension For patients with hypertension and renal impairment, the recommended initial dose is 1.25 mg ramipril capsules once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 5 mg. Heart Failure Post-Myocardial Infarction For patients with heart failure and renal impairment, the recommended initial dose is 1.25 mg ramipril capsules once daily. The dose may be increased to 1.25 mg twice daily, and up to a maximum dose of 2.5 mg twice daily depending on clinical response and tolerability.Volume Depletion or Renal Artery Stenosis Blood pressure decreases associated with any dose of ramipril capsules depend, in part, on the presence or absence of volume depletion (e.g., past and current diuretic use) or the presence or absence of renal artery stenosis. If such circumstances are suspected to be present, initiate dosing at 1.25 mg once daily. Adjust dosage according to blood pressure response.
Ondansetron

Ondansetron

Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy

The recommended adult oral dosage of ondansetron is 24 mg given as three 8 mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m2. Multiday, single-dose administration of a 24 mg dosage has not been studied.

Pediatric Use

There is no experience with the use of a 24 mg dosage in pediatric patients.

Geriatric Use

The dosage recommendation is the same as for the general population.

Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy

The recommended adult oral dosage is 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ondansetron oral solution given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ondansetron oral solution should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Pediatric Use

For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of ondansetron oral solution given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of ondansetron oral solution should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.

Geriatric Use

The dosage is the same as for the general population.

Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen

The recommended oral dosage is 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ondansetron oral solution given 3 times a day. For total body irradiation, 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ondansetron oral solution should be administered 1 to 2 hours before each fraction of radiotherapy administered each day. For single high-dose fraction radiotherapy to the abdomen, 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ondansetron oral solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy. For daily fractionated radiotherapy to the abdomen, 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ondansetron oral solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

Pediatric Use

There is no experience with the use of ondansetron oral solution in the prevention of radiation-induced nausea and vomiting in pediatric patients.

Geriatric Use

The dosage recommendation is the same as for the general population.

Postoperative Nausea and Vomiting

The recommended dosage is 20 mL (4 teaspoonfuls equivalent to 16 mg of ondansetron) of ondansetron oral solution 1 hour before induction of anesthesia.

Pediatric Use

There is no experience with the use of ondansetron oral solution in the prevention of postoperative nausea and vomiting in pediatric patients.

Geriatric Use

The dosage is the same as for the general population.

Dosage Adjustment for Patients With Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.

Dosage Adjustment for Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh2 score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.
Ondansetron Hydrochlori...

Ondansetron Hydrochloride

Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy The recommended adult oral dosage of ondansetron tablets is 24 mg given as three 8 mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m2. Multiday, single-dose administration of a 24 mg dosage has not been studied.Pediatric UseThere is no experience with the use of a 24 mg dosage in pediatric patients.Geriatric UseThe dosage recommendation is the same as for the general population. Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy The recommended adult oral dosage is one 8 mg ondansetron tablet given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg ondansetron tablet should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.Pediatric UseFor pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4 mg ondansetron tablet given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4 mg ondansetron tablet should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.Geriatric UseThe dosage is the same as for the general population. Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen The recommended oral dosage is one 8 mg ondansetron tablet given 3 times a day. For total body irradiation, one 8 mg ondansetron tablet should be administered 1 to 2 hours before each fraction of radiotherapy administered each day. For single high-dose fraction radiotherapy to the abdomen, one 8 mg ondansetron tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy. For daily fractionated radiotherapy to the abdomen, one 8 mg ondansetron tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.Pediatric UseThere is no experience with the use of ondansetron tablets in the prevention of radiation-induced nausea and vomiting in pediatric patients.Geriatric UseThe dosage recommendation is the same as for the general population. Postoperative Nausea and Vomiting The recommended dosage is 16 mg given as two 8 mg ondansetron tablets 1 hour before induction of anesthesia.Pediatric UseThere is no experience with the use of ondansetron tablets in the prevention of postoperative nausea and vomiting in pediatric patients.Geriatric UseThe dosage is the same as for the general population. Dosage Adjustment for Patients With Impaired Renal Function The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron. Dosage Adjustment for Patients With Impaired Hepatic Function In patients with severe hepatic impairment (Child-Pugh2 score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.
Ondansetron

Ondansetron

Instructions for Use/Handling Ondansetron Orally Disintegrating Tablets Do not attempt to push ondansetron orally disintegrating tablets through the foil backing. With dry hands, remove the tablet from the bottle or PEEL BACK the foil backing of 1 blister and GENTLY remove the tablet. IMMEDIATELY place the ondansetron orally disintegrating tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary. Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy The recommended adult oral dosage of ondansetron orally disintegrating tablets is 24 mg given as three 8 mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m2. Multiday, single-dose administration of a 24 mg dosage has not been studied. Pediatric Use There is no experience with the use of a 24 mg dosage in pediatric patients. Geriatric Use The dosage recommendation is the same as for the general population. Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy The recommended adult oral dosage is one 8 mg ondansetron orally disintegrating tablet given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg ondansetron orally disintegrating tablet should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.Pediatric UseFor pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4 mg ondansetron orally disintegrating tablet given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4 mg ondansetron orally disintegrating tablet should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy. Geriatric Use The dosage is the same as for the general population. Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen The recommended oral dosage is one 8 mg ondansetron orally disintegrating tablet given 3 times a day. For total body irradiation, one 8 mg ondansetron orally disintegrating tablet should be administered 1 to 2 hours before each fraction of radiotherapy administered each day. For single high-dose fraction radiotherapy to the abdomen, one 8 mg ondansetron orally disintegrating tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy. For daily fractionated radiotherapy to the abdomen, one 8 mg ondansetron orally disintegrating tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.Pediatric UseThere is no experience with the use of ondansetron orally disintegrating tablets in the prevention of radiation-induced nausea and vomiting in pediatric patients.Geriatric UseThe dosage recommendation is the same as for the general population. Postoperative Nausea and Vomiting The recommended dosage is 16 mg given as two 8 mg ondansetron orally disintegrating tablets 1 hour before induction of anesthesia.Pediatric UseThere is no experience with the use of ondansetron orally disintegrating tablets in the prevention of postoperative nausea and vomiting in pediatric patients.Geriatric UseThe dosage is the same as for the general population. Dosage Adjustment for Patients With Impaired Renal Function The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron. Dosage Adjustment for Patients With Impaired Hepatic Function In patients with severe hepatic impairment (Child-Pugh2 score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.

Aurobindo Pharma Limited

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