Mylan Institutional Inc.

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Mylan Institutional Inc. Drugs

Carbon Dioxide Gas

Carbon Dioxide Gas

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.
Coats Aloe Lotion 85%

Coats Aloe Lotion 85%

The usual dose of Triamterene and Hydrochlorothiazide Tablets 37.5 mg/25 mg is one or two tablets daily, given as a single dose, with appropriate monitoring of serum potassium (see WARNINGS). The usual dose of Triamterene and Hydrochlorothiazide Tablets 75 mg/50 mg is one tablet daily, with appropriate monitoring of serum potassium (see WARNINGS). There is no experience with the use of more than one 75 mg/50 mg (75 mg triamterene and 50 mg hydrochlorothiazide) tablet daily or more than two 37.5 mg/25 mg (37.5 mg triamterene and 25 mg hydrochlorothiazide) tablets daily. Clinical experience with the administration of two 37.5 mg/25 mg tablets daily in divided doses (rather than as a single dose) suggests an increased risk of electrolyte imbalance and renal dysfunction.

Patients receiving 50 mg of hydrochlorothiazide who become hypokalemic may be transferred to this 75 mg/50 mg product directly. Patients receiving 25 mg hydrochlorothiazide who become hypokalemic may be transferred to this 37.5 mg/25 mg product directly.

In patients requiring hydrochlorothiazide therapy and in whom hypokalemia cannot be risked, therapy may be initiated with 37.5 mg/25 mg of triamterene and hydrochlorothiazide. If an optimal blood pressure response is not obtained with 37.5 mg/25 mg of triamterene and hydrochlorothiazide, the dose should be increased to two 37.5 mg/25 mg tablets daily as a single dose, or one 75 mg/50 mg tablet daily. If blood pressure still is not controlled, another antihypertensive agent may be added (see PRECAUTIONS: Drug Interactions).

Clinical studies have shown that patients taking less bioavailable formulations of triamterene and hydrochlorothiazide in daily doses of 25 mg to 50 mg hydrochlorothiazide and 50 mg to 100 mg triamterene may be safely changed to one triamterene and hydrochlorothiazide 37.5 mg/25 mg tablet daily. All patients changed from less bioavailable formulations to this product should be monitored clinically and for serum potassium after the transfer.
Catacure

Catacure

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 USP 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 USP should be restricted to patients who have been taking simvastatin, USP 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 USP who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, USP 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 USP, patients unable to achieve their LDL-C goal utilizing the 40 mg dose of simvastatin tablets USP 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 USP 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 USP 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 USP 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 USP should be reduced by 50% if initiating lomitapide. Simvastatin tablets USP dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin tablets USP, 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 Guidelines1and Clinical Studies (14.2)]. Adjustments should be made at intervals of 4 weeks or more.

1 National 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 USP 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 USP 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)].
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)].
Digitek

Digitek

2.1 Important Dosing and Administration Information

In selecting a DIGITEK® (digoxin tablets) dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.

Consider interruption or reduction in digoxin dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].

Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients or patients with very low body weight.

2.2 Loading Dosing Regimen in Adults and Pediatric Patients

For adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended DIGITEK® (digoxin tablets) Oral Loading Dose
Age

Total Oral Loading Dose (mcg/kg) Administer half the total loading dose initially, then¼ the loading dose every 6 to 8 hours twice

5 years to 10 years

20 to 45

Adults and pediatric patients over 10 years

10 to 15

mcg = micrograms

2.3 Maintenance Dosing in Adults and Pediatric Patients over 10 Years Old

The maintenance dose is based on lean body weight, renal function, age and concomitant products [see Clinical Pharmacology (12.3)].

The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels and toxicity.
Table 2. Recommended Starting DIGITEK® (digoxin tablets) Maintenance Dosage in Adults and Pediatric Patients over 10 Years Old
Age

Total Oral Maintenance Dose, mcg/kg/day (given once daily)

Adults and pediatric patients over 10 years

3.4 to 5.1

mcg = micrograms

Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):

Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100(% Daily Loss = 14 + Creatinine clearance/5)

Reduce the dose of DIGITEK® (digoxin tablets) in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of DIGITEK® (digoxin tablets) in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Function* * Doses are rounded to the nearest dose possible using whole and/or half DIGITEK ® (digoxin tablets) tablets. Recommended doses approximately 30% lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. † For adults, creatinine clearance was corrected to 70 kg body weight or 1.73 m 2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85. For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m 2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.GFR (mL/min/1.73 m 2) = (k x Height)/Scr ‡ The doses listed assume average body composition. § If no loading dose administered.
Corrected Creatinine Clearance†

Lean Body Weight‡

Numberof DaysBeforeSteadyStateAchieved§

kg

40

50

60

70

80

90

100

lb

88

110

132

154

176

198

220

10 mL/min

62.5*

125

125

187.5

187.5

187.5

250

19

20 mL/min

125

125

125

187.5

187.5

250

250

16

30 mL/min

125

125

187.5

187.5

250

250

312.5

14

40 mL/min

125

187.5

187.5

250

250

312.5

312.5

13

50 mL/min

125

187.5

187.5

250

250

312.5

312.5

12

60 mL/min

125

187.5

250

250

312.5

312.5

375

11

70 mL/min

187.5

187.5

250

250

312.5

375

375

10

80 mL/min

187.5

187.5

250

312.5

312.5

375

437.5

9

90 mL/min

187.5

250

250

312.5

375

437.5

437.5

8

100 mL/min

187.5

250

312.5

312.5

375

437.5

500

7

2.4 Maintenance Dosing in Pediatric Patients less than 10 Years Old

The starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting DIGITEK® (digoxin tablets) Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old
Age

Oral Maintenance Dose, mcg/kg/dose

5 years to 10 years

3.2 to 6.4 Twice daily

Table 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given twice daily) of DIGITEK® (digoxin tablets) in Pediatric Patients between 5 and 10 Years of Age* Based upon Lean Body Weight and Renal Function*, † * Recommended are doses to be given twice daily. † The doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. ‡ The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3. § If no loading dose administered.
Corrected Creatinine Clearance‡

Lean Body Weight

Number ofDaysBeforeSteadyStateAchieved§

kg

20

30

40

50

60

lb

44

66

88

110

132

10 mL/min

-

62.5

62.5*

125

125

19

20 mL/min

62.5

62.5

125

125

125

16

30 mL/min

62.5

62.5*

125

125

187.5

14

40 mL/min

62.5

62.5*

125

187.5

187.5

13

50 mL/min

62.5

125

125

187.5

187.5

12

60 mL/min

62.5

125

125

187.5

250

11

70 mL/min

62.5

125

187.5

187.5

250

10

80 mL/min

62.5*

125

187.5

187.5

250

9

90 mL/min

62.5*

125

187.5

250

250

8

100 mL/min

62.5*

125

187.5

250

312.5

7

2.5 Monitoring to Assess Safety, Efficacy and Therapeutic Blood Levels

Monitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy and blood levels.

Serum digoxin levels < 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.

Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the DIGITEK® (digoxin tablets) dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting DIGITEK® (digoxin tablets) and correct post-treatment values by the reported baseline level.

Obtain serum digoxin concentrations just before the next scheduled DIGITEK® (digoxin tablets) dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10% to 25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.

2.6 Switching from Intravenous Digoxin to Oral Digoxin

When switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous DIGITEK® (digoxin tablets)
Absolute Bioavailability

Equivalent Doses (mcg)

DIGITEK® (digoxin tablets)

60% to 80%

62.5

125

250

500

Digoxin Intravenous Injection

100%

50

100

200

400
Metronidazole

Metronidazole

Trichomoniasis In the Female One-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 Male

Treatment should be individualized as it is for the female.

Amebiasis

Adults

For 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 patients

35 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 (approx. 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 Adjustments

Patients with Severe Hepatic Impairment

For patients with severe hepatic

impairment (Child-Pugh C), the dose of metronidazole should be reduced by 50% (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Patients Undergoing Hemodialysis:

Hemodialysis 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).
Lidothol

Lidothol

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 mg 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 tablets is 75 mg once daily orally, administered in combination with aspirin (75 mg 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 tablets 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. Omeprazole and esomeprazole significantly reduce the antiplatelet activity of clopidogrel. 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)].
Celecoxib

Celecoxib

Use lowest effective dose for the shortest duration consistent with treatment goals for the individual patient.

These doses can be given without regard to timing of meals.

2.1 Osteoarthritis

For relief of the signs and symptoms of OA the recommended oral dose is 200 mg per day administered as a single dose or as 100 mg twice daily.

2.2 Rheumatoid Arthritis

For relief of the signs and symptoms of RA the recommended oral dose is 100 mg to 200 mg twice daily.

2.3 Juvenile Rheumatoid Arthritis

For the relief of the signs and symptoms of JRA the recommended oral dose for pediatric patients (age 2 years and older) is based on weight. For patients ≥ 10 kg to ≤ 25 kg the recommended dose is 50 mg twice daily. For patients > 25 kg the recommended dose is 100 mg twice daily.

For patients who have difficulty swallowing capsules, the contents of a celecoxib capsule can be added to applesauce. The entire capsule contents are carefully emptied onto a level teaspoon of cool or room temperature applesauce and ingested immediately with water. The sprinkled capsule contents on applesauce are stable for up to 6 hours under refrigerated conditions (2 to 8°C/ 35 to 45°F).

2.4 Ankylosing Spondylitis

For the management of the signs and symptoms of AS, the recommended dose of celecoxib capsules is 200 mg daily in single (once per day) or divided (twice per day) doses. If no effect is observed after 6 weeks, a trial of 400 mg daily may be worthwhile. If no effect is observed after 6 weeks on 400 mg daily, a response is not likely and consideration should be given to alternate treatment options.

2.5 Management of Acute Pain and Treatment of Primary Dysmenorrhea

The recommended dose of celecoxib capsules is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed.

2.6 Special Populations

Hepatic Insufficiency

The daily recommended dose of celecoxib capsules in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by 50%. The use of celecoxib in patients with severe hepatic impairment is not recommended [see Warnings and Precautions (5.5), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Poor Metabolizers of CYP2C9 Substrates

Patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered celecoxib with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers (i.e., CYP2C9*3/*3). Consider using alternative management in JRA patients who are poor metabolizers [see Use in Specific Populations (8.8), and Clinical Pharmacology (12.5)].
Phentermine Hydrochlori...

Phentermine Hydrochloride

Breast Cancer: 160 mg/day (40 mg qid).

Endometrial Carcinoma: 40 to 320 mg/day in divided doses.

At least 2 months of continuous treatment is considered an adequate period for determining the efficacy of Megestrol Acetate Tablets USP.
Herbion Naturals Orange...

Herbion Naturals Orange Cough Drops

Sulfamethoxazole and trimethoprim 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:

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
22

10

–

44

20

1

66

30

1½

88

40

2 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 30

Usual standard regimen

15–30

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 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
18

8

–

35

16

1

53

24

1½

70

32

2 or 1 DS tablet

88

40

2½

106

48

3 or 1½ DS tablets

141

64

4 or 2 DS tablets

176

80

5 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

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) Tablets
0.26

–

0.53

½

1.06

1

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.
Pain And Fever

Pain And Fever

Motion Sickness

The initial dose of 25 mg to 50 mg of meclizine hydrochloride tablets should be taken one hour prior to travel for protection against motion sickness. Thereafter, the dose may be repeated every 24 hours for the duration of the journey.
Eszopiclone

Eszopiclone

Use the lowest effective dose for the patient.

2.1 Dosage in Adults

The recommended starting dose is 1 mg. Dosing can be raised to 2 mg or 3 mg if clinically indicated. In some patients, the higher morning blood levels of eszopiclone tablets following use of the 2 mg or 3 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 eszopiclone tablets should not exceed 3 mg, once daily immediately before bedtime [see Warnings and Precautions (5.6)].

2.2 Geriatric or Debilitated Patients

The total dose of eszopiclone tablets should not exceed 2 mg in elderly or debilitated patients.

2.3 Patients with Severe Hepatic Impairment, or Taking Potent CYP3A4 Inhibitors

In patients with severe hepatic impairment, or in patients coadministered eszopiclone tablets with potent CYP3A4 inhibitors, the total dose of eszopiclone tablets should not exceed 2 mg [see Warnings and Precautions (5.7)].

2.4 Use with CNS Depressants

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

2.5 Administration with Food

Taking eszopiclone tablets with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of eszopiclone tablets on sleep latency [see Clinical Pharmacology (12.3)].
Diltiazem Hydrochloride...

Diltiazem Hydrochloride

Primary Hyperaldosteronism

Spironolactone tablets may be employed as an initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

Long Test

Spironolactone tablets are administered at a daily dosage of 400 mg for 3 to 4 weeks. Correction of hypokalemia and of hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.

Short Test

Spironolactone tablets are administered at a daily dosage of 400 mg for 4 days. If serum potassium increases during spironolactone tablet administration but drops when spironolactone tablets are discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.

After the diagnosis of hyperaldosteronism has been established by more definitive testing procedures, spironolactone tablets may be administered in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone tablets may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

Edema in Adults (Congestive Heart Failure, Hepatic Cirrhosis or Nephrotic Syndrome)

An initial daily dosage of 100 mg of spironolactone tablets administered in either single or divided doses is recommended, but may range from 25 mg to 200 mg daily. When given as the sole agent for diuresis, spironolactone tablets should be continued for at least 5 days at the initial dosage level, after which it may be adjusted to the optimal therapeutic or maintenance level administered in either single or divided daily doses. If, after 5 days, an adequate diuretic response to spironolactone tablets has not occurred, a second diuretic that acts more proximally in the renal tubule may be added to the regimen. Because of the additive effect of spironolactone tablets when administered concurrently with such diuretics, an enhanced diuresis usually begins on the first day of combined treatment; combined therapy is indicated when more rapid diuresis is desired. The dosage of spironolactone tablets should remain unchanged when other diuretic therapy is added.

Essential Hypertension

For adults, an initial daily dosage of 50 mg to 100 mg of spironolactone tablets administered in either single or divided doses is recommended. Spironolactone tablets may also be given with diuretics that act more proximally in the renal tubule or with other antihypertensive agents. Treatment with spironolactone tablets should be continued for at least 2 weeks, since the maximum response may not occur before this time. Subsequently, dosage should be adjusted according to the response of the patient.

Hypokalemia

Spironolactone tablets in a dosage ranging from 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia, when oral potassium supplements or other potassium-sparing regimens are considered inappropriate.

Severe Heart Failure in Conjunction with Standard Therapy (NYHA Class III to IV)

Treatment should be initiated with spironolactone tablets 25 mg once daily if the patient's serum potassium is ≤ 5 mEq/L and the patient's serum creatinine is ≤ 2.5 mg/dL. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily as clinically indicated. Patients who do not tolerate 25 mg once daily may have their dosage reduced to 25 mg every other day. See WARNINGS: Hyperkalemia In Patients With Severe Heart Failure for advice on monitoring serum potassium and serum creatinine.
Spectinomycin

Spectinomycin

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)].
Tacrolimus

Tacrolimus

NOTE: Anaphylactic reactions have occurred with injectables containing castor oil derivatives. See WARNINGS.

Tacrolimus Capsules
Summary of Initial Oral Dosage Recommendations and Observed Whole Blood Trough Concentrations * Note: two divided doses, q12h † In a second smaller study, the initial dose of tacrolimus was 0.15 to 0.2 mg/kg/day and observed tacrolimus concentrations were 6 to 16 ng/mL during month 1 to 3 and 5 to 12 ng/mL during month 4 to 12 (see CLINICAL STUDIES).
Patient Population

Recommended Initial Oral Dose*

Typical Whole Blood Trough Concentrations

Adult kidney transplant patients In combination with azathioprine

0.2 mg/kg/day

month 1 to 3: 7 to 20 ng/mLmonth 4 to 12: 5 to 15 ng/mL

In combination with MMF/IL-2 receptor antagonist†

0.1 mg/kg/day

month 1 to 12: 4 to 11 ng/mL

Adult liver transplant patients

0.10 to 0.15 mg/kg/day

month 1 to 12: 5 to 20 ng/mL

Pediatric liver transplant patients

0.15 to 0.20 mg/kg/day

month 1 to 12: 5 to 20 ng/mL

Liver Transplantation

It is recommended that patients initiate oral therapy with tacrolimus capsules if possible. If IV therapy is necessary, conversion from IV to oral tacrolimus is recommended as soon as oral therapy can be tolerated. This usually occurs within 2 to 3 days. The initial dose of tacrolimus should be administered no sooner than 6 hours after transplantation. In a patient receiving an IV infusion, the first dose of oral therapy should be given 8 to 12 hours after discontinuing the IV infusion. The recommended starting oral dose of tacrolimus capsules is 0.10 to 0.15 mg/kg/day administered in two divided daily doses every 12 hours. Coadministered grapefruit juice has been reported to increase tacrolimus blood trough concentrations in liver transplant patients. (See Drugs that May Alter Tacrolimus Concentrations.)

Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower tacrolimus dosages may be sufficient as maintenance therapy. Adjunct therapy with adrenal corticosteroids is recommended early post transplant.

Dosage and typical tacrolimus whole blood trough concentrations are shown in the table above; blood concentration details are described in Blood Concentration Monitoring: Liver Transplantation below.

Kidney Transplantation

The recommended starting oral dose of tacrolimus (administered every 12 hours in two divided doses) is 0.2 mg/kg/day when used in combination with azathioprine or 0.1 mg/kg/day when used in combination with MMF and IL-2 receptor antagonist (see CLINICAL STUDIES). The initial dose of tacrolimus may be administered within 24 hours of transplantation, but should be delayed until renal function has recovered (as indicated for example by a serum creatinine ≤ 4 mg/dL). Black patients may require higher doses to achieve comparable blood concentrations. Dosage and typical tacrolimus whole blood trough concentrations are shown in the table above; blood concentration details are described in Blood Concentration Monitoring: Kidney Transplantation below.

The data in kidney transplant patients indicate that the Black patients required a higher dose to attain comparable trough concentrations compared to Caucasian patients.

Time After Transplant

Caucasian n = 114

Black n = 56

Dose (mg/kg)

Trough Concentrations (ng/mL)

Dose (mg/kg)

Trough Concentrations (ng/mL)

Day 7

0.18

12

0.23

10.9

Month 1

0.17

12.8

0.26

12.9

Month 6

0.14

11.8

0.24

11.5

Month 12

0.13

10.1

0.19

11

Pediatric Patients

Pediatric liver transplantation patients without preexisting renal or hepatic dysfunction have required and tolerated higher doses than adults to achieve similar blood concentrations. Therefore, it is recommended that therapy be initiated in pediatric patients at a starting IV dose of 0.03 to 0.05 mg/kg/day and a starting oral dose of 0.15 to 0.20 mg/kg/day. Dose adjustments may be required. Experience in pediatric kidney transplantation patients is limited.

Patients with Hepatic or Renal Dysfunction

Due to the reduced clearance and prolonged half-life, patients with severe hepatic impairment (Pugh ≥ 10) may require lower doses of tacrolimus. Close monitoring of blood concentrations is warranted.

Due to the potential for nephrotoxicity, patients with renal or hepatic impairment should receive doses at the lowest value of the recommended IV and oral dosing ranges. Further reductions in dose below these ranges may be required. Tacrolimus therapy usually should be delayed up to 48 hours or longer in patients with postoperative oliguria.

Conversion from One Immunosuppressive Regimen to Another

Tacrolimus capsules should not be used simultaneously with cyclosporine. Tacrolimus or cyclosporine should be discontinued at least 24 hours before initiating the other. In the presence of elevated tacrolimus or cyclosporine concentrations, dosing with the other drug usually should be further delayed.

Blood Concentration Monitoring

Monitoring of tacrolimus blood concentrations in conjunction with other laboratory and clinical parameters is considered an essential aid to patient management for the evaluation of rejection, toxicity, dose adjustments and compliance. Factors influencing frequency of monitoring include but are not limited to hepatic or renal dysfunction, the addition or discontinuation of potentially interacting drugs and the post transplant time. Blood concentration monitoring is not a replacement for renal and liver function monitoring and tissue biopsies.

Two methods have been used for the assay of tacrolimus, a microparticle enzyme immunoassay (MEIA) and ELISA. Both methods have the same monoclonal antibody for tacrolimus. Comparison of the concentrations in published literature to patient concentrations using the current assays must be made with detailed knowledge of the assay methods and biological matrices employed. Whole blood is the matrix of choice and specimens should be collected into tubes containing ethylene diamine tetraacetic acid (EDTA) anti-coagulant. Heparin anti-coagulation is not recommended because of the tendency to form clots on storage. Samples which are not analyzed immediately should be stored at room temperature or in a refrigerator and assayed within 7 days; if samples are to be kept longer they should be deep frozen at -20° C for up to 12 months.

Liver Transplantation

Although there is a lack of direct correlation between tacrolimus concentrations and drug efficacy, data from Phase II and III studies of liver transplant patients have shown an increasing incidence of adverse events with increasing trough blood concentrations. Most patients are stable when trough whole blood concentrations are maintained between 5 to 20 ng/mL. Long-term post transplant patients often are maintained at the low end of this target range.

Data from the U.S. clinical trial show that tacrolimus whole blood concentrations, as measured by ELISA, were most variable during the first week post transplantation. After this early period, the median trough blood concentrations, measured at intervals from the second week to one year post transplantation, ranged from 9.8 ng/mL to 19.4 ng/mL.

Therapeutic Drug Monitoring, 1995, Volume 17, Number 6 contains a consensus document and several position papers regarding the therapeutic monitoring of tacrolimus from the 1995 International Consensus Conference on Immunosuppressive Drugs. Refer to these manuscripts for further discussions of tacrolimus monitoring.

Kidney Transplantation

Data from a Phase 3 study of tacrolimus in conjunction with azathioprine indicate that trough concentrations of tacrolimus in whole blood, as measured by IMx® were most variable during the first week of dosing. During the first 3 months of that trial, 80% of the patients maintained trough concentrations between 7 to 20 ng/mL, and then between 5 to 15 ng/mL, through one year.

In a separate clinical trial of tacrolimus in conjunction with MMF and daclizumab, approximately 80% of patients maintained tacrolimus whole blood concentrations between 4 to 11 ng/mL through one year post transplant.

In another clinical trial of tacrolimus in conjunction with MMF and basiliximab, approximately 80% of patients maintained tacrolimus whole trough blood concentrations between 6 to 16 ng/mL during month 1 to 3 and, then, between 5 to 12 ng/mL from month 4 through one year.

The relative risks of toxicity and efficacy failure are related to tacrolimus whole blood trough concentrations. Therefore, monitoring of whole blood trough concentrations is recommended to assist in the clinical evaluation of toxicity and efficacy failure.
Nabumetone

Nabumetone

Optimal dosage should be established by individual titration of the components (see BOXED WARNING).

Edema in Adults (Congestive Heart Failure, Hepatic Cirrhosis or Nephrotic Syndrome)

The usual maintenance dose of spironolactone and hydrochlorothiazide tablets is 100 mg each of spironolactone and hydrochlorothiazide daily, administered in a single-dose or in divided doses, but may range from 25 mg to 200 mg of each component daily depending on the response to the initial titration. In some instances it may be desirable to administer separate tablets of either spironolactone or hydrochlorothiazide in addition to spironolactone and hydrochlorothiazide tablets in order to provide optimal individual therapy.

The onset of diuresis with spironolactone and hydrochlorothiazide tablets occurs promptly and, due to prolonged effect of the spironolactone component, persists for 2 to 3 days after spironolactone and hydrochlorothiazide tablets are discontinued.

Essential Hypertension

Although the dosage will vary depending on the results of titration of the individual ingredients, many patients will be found to have an optimal response to 50 mg to 100 mg each of spironolactone and hydrochlorothiazide daily, given in a single-dose or in divided doses.

Concurrent potassium supplementation is not recommended when spironolactone and hydrochlorothiazide tablets are used in the long-term management of hypertension or in the treatment of most edematous conditions, since the spironolactone content of spironolactone and hydrochlorothiazide tablets is usually sufficient to minimize loss induced by the hydrochlorothiazide component.
6 Liver

6 Liver

While the recommended usual adult dose is 15 mg before retiring, 7.5 mg may be sufficient for some patients, and others may need 30 mg. In transient insomnia, a 7.5 mg dose may be sufficient to improve sleep latency. In elderly or debilitated patients, it is recommended that therapy be initiated with 7.5 mg until individual responses are determined.
Cerebraplex

Cerebraplex

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 is 1 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.
Nadolol

Nadolol

DOSAGE MUST BE INDIVIDUALIZED. NADOLOL TABLETS MAY BE ADMINISTERED WITHOUT REGARD TO MEALS.

Angina Pectoris

The usual initial dose is 40 mg nadolol once daily. Dosage may be gradually increased in 40 mg to 80 mg increments at 3 to 7 day intervals until optimum clinical response is obtained or there is pronounced slowing of the heart rate. The usual maintenance dose is 40 mg or 80 mg administered once daily. Doses up to 160 mg or 240 mg administered once daily may be needed.

The usefulness and safety in angina pectoris of dosages exceeding 240 mg per day have not been established. If treatment is to be discontinued, reduce the dosage gradually over a period of 1 to 2 weeks (see WARNINGS).

Hypertension

The usual initial dose is 40 mg nadolol once daily, whether it is used alone or in addition to diuretic therapy. Dosage may be gradually increased in 40 mg to 80 mg increments until optimum blood pressure reduction is achieved. The usual maintenance dose is 40 mg or 80 mg administered once daily. Doses up to 240 mg or 320 mg administered once daily may be needed.

Dosage Adjustment in Renal Failure

Absorbed nadolol is excreted principally by the kidneys and, although nonrenal elimination does occur, dosage adjustments are necessary in patients with renal impairment. The following dose intervals are recommended:
Creatinine Clearance (mL/min/1.73m2) Dosage Interval (hours)
> 50

24

31 to 50

24 to 36

10 to 30

24 to 48

< 10

40 to 60
Pentoxifylline

Pentoxifylline

The usual dosage of pentoxifylline in extended-release tablet form is one tablet (400 mg) three times a day with meals.

While the effect of pentoxifylline may be seen within 2 to 4 weeks, it is recommended that treatment be continued for at least 8 weeks. Efficacy has been demonstrated in double-blind clinical studies of 6 months duration.

Digestive and central nervous system side effects are dose related. If patients develop these effects it is recommended that the dosage be lowered to one tablet twice a day (800 mg/day). If side effects persist at this lower dosage, the administration of pentoxifylline should be discontinued.
Premier Value Chest And...

Premier Value Chest And Sinus Congestion Relief

The dose of amantadine hydrochloride capsules may need reduction in patients with congestive heart failure, peripheral edema, orthostatic hypotension, or impaired renal function (see Dosage for Impaired Renal Function).

Dosage for Prophylaxis and Treatment of Uncomplicated Influenza A Virus Illness

Adult

The adult daily dosage of amantadine hydrochloride capsules is 200 mg; two 100 mg capsules as a single daily dose. The daily dosage may be split into one capsule of 100 mg twice a day. If central nervous system effects develop in once-a-day dosage, a split dosage schedule may reduce such complaints. In persons 65 years of age or older, the daily dosage of amantadine hydrochloride capsules is 100 mg.

A 100 mg daily dose has also been shown in experimental challenge studies to be effective as prophylaxis in healthy adults who are not at high risk for influenza-related complications. However, it has not been demonstrated that a 100 mg daily dose is as effective as a 200 mg daily dose for prophylaxis, nor has the 100 mg daily dose been studied in the treatment of acute influenza illness. In recent clinical trials, the incidence of central nervous system (CNS) side effects associated with the 100 mg daily dose was at or near the level of placebo. The 100 mg dose is recommended for persons who have demonstrated intolerance to 200 mg of amantadine hydrochloride daily because of CNS or other toxicities.

Pediatric Patients

1 yr. to 9 yrs. of age

The total daily dose should be calculated on the basis of 2 to 4 mg/lb/day (4.4 to 8.8 mg/kg/day), but not to exceed 150 mg per day.

9 yrs. to 12 yrs. of age

The total daily dose is 200 mg given as one capsule of 100 mg twice a day. The 100 mg daily dose has not been studied in this pediatric population. Therefore, there are no data which demonstrate that this dose is as effective as or is safer than the 200 mg daily dose in this patient population.

Prophylactic dosing should be started in anticipation of an influenza A outbreak and before or after contact with individuals with influenza A virus respiratory tract illness.

Amantadine hydrochloride capsules should be continued daily for at least 10 days following a known exposure. If amantadine is used chemoprophylactically in conjunction with inactivated influenza A virus vaccine until protective antibody responses develop, then it should be administered for 2 to 4 weeks after the vaccine has been given. When inactivated influenza A virus vaccine is unavailable or contraindicated, amantadine hydrochloride capsules should be administered for the duration of known influenza A in the community because of repeated and unknown exposure.

Treatment of influenza A virus illness should be started as soon as possible, preferably within 24 to 48 hours after onset of signs and symptoms, and should be continued for 24 to 48 hours after the disappearance of signs and symptoms.

Dosage for Parkinsonism

Adult

The usual dose of amantadine hydrochloride capsules is 100 mg twice a day when used alone. Amantadine has an onset of action usually within 48 hours.

The initial dose of amantadine hydrochloride capsules is 100 mg daily for patients with serious associated medical illnesses or who are receiving high doses of other antiparkinson drugs. After one to several weeks at 100 mg once daily, the dose may be increased to 100 mg twice daily, if necessary.

Occasionally, patients whose responses are not optimal with amantadine hydrochloride capsules at 200 mg daily may benefit from an increase up to 400 mg daily in divided doses. However, such patients should be supervised closely by their physicians.

Patients initially deriving benefit from amantadine hydrochloride capsules not uncommonly experience a fall-off of effectiveness after a few months. Benefit may be regained by increasing the dose to 300 mg daily. Alternatively, temporary discontinuation of amantadine hydrochloride capsules for several weeks, followed by reinitiation of the drug, may result in regaining benefit in some patients. A decision to use other antiparkinson drugs may be necessary.

Dosage for Concomitant Therapy

Some patients who do not respond to anticholinergic antiparkinson drugs may respond to amantadine hydrochloride capsules. When amantadine hydrochloride capsules or anticholinergic antiparkinson drugs are each used with marginal benefit, concomitant use may produce additional benefit.

When amantadine and levodopa are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Amantadine hydrochloride capsules should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal benefit.

When amantadine is added to optimal well-tolerated doses of levodopa, additional benefit may result, including smoothing out the fluctuations in improvement which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of amantadine hydrochloride capsules.

Dosage for Drug Induced Extrapyramidal Reactions

Adult

The usual dose of amantadine hydrochloride capsules is 100 mg twice a day. Occasionally, patients whose responses are not optimal with amantadine hydrochloride capsules at 200 mg daily may benefit from an increase up to 300 mg daily in divided doses.

Dosage for Impaired Renal Function

Depending upon creatinine clearance, the following dosage adjustments are recommended:

CREATININE CLEARANCE

(mL/min/1.73m2)

AMANTADINE

HYDROCHLORIDE

CAPSULES DOSAGE

30 to 50

200 mg 1st day and 100 mg each day thereafter

15 to 29

200 mg 1st day followed by 100 mg on

alternate days

<15

200 mg every 7 days

The recommended dosage for patients on hemodialysis is 200 mg every 7 days.
Selsun Blue Normal To O...

Selsun Blue Normal To Oily

Serum concentrations should be monitored in changing from extended phenytoin sodium capsules, USP, 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 7 to 10 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 7 to 10 days.

Adult Dosage

Divided Daily Dosage

Patients 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 Dosage

In 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 Dose

Some 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 is divided into three doses (400 mg, 300 mg, 300 mg) and administered at 2 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).
Triamterene And Hydroch...

Triamterene And Hydrochlorothiazide

The usual dose of triamterene and hydrochlorothiazide capsules is one or two capsules given once daily, with appropriate monitoring of serum potassium and of the clinical effect. (See WARNINGS, Hyperkalemia.)
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).
Topiramate

Topiramate

2.1 Epilepsy

It is not necessary to monitor topiramate plasma concentrations to optimize topiramate 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

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 1000 mg/day) have not been shown to improve responses in dose response studies in adults with partial onset seizures. Daily doses above 1600 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 tablets 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.
Verapamil Hydrochloride...

Verapamil Hydrochloride

Essential Hypertension

The dose of verapamil hydrochloride extended-release capsules should be individualized by titration. The usual daily dose of extended-release verapamil hydrochloride capsules in clinical trials has been 240 mg given by mouth once daily in the morning. However, initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (e.g., elderly, small people, etc.). Upward titration should be based on therapeutic efficacy and safety evaluated approximately 24 hours after dosing. The antihypertensive effects of verapamil hydrochloride extended-release capsules are evident within the first week of therapy.

If adequate response is not obtained with 120 mg of verapamil hydrochloride extended-release capsules, the dose may be titrated upward in the following manner:
• 180 mg in the morning, • 240 mg in the morning, • 360 mg in the morning, • 480 mg in the morning.
Verapamil extended-release capsules are for once a day administration. When switching from immediate-release verapamil to verapamil hydrochloride extended-release capsules, the same total daily dose of verapamil hydrochloride extended-release capsules can be used.

As with immediate-release verapamil, dosages of verapamil hydrochloride extended-release capsules should be individualized and titration may be needed in some patients.

Sprinkling the Capsule Contents on Food

Verapamil hydrochloride extended-release bead filled capsules may also be administered by carefully opening the capsule and sprinkling the beads on a spoonful of applesauce. The applesauce should be swallowed immediately without chewing and followed with a glass of cool water to ensure complete swallowing of the beads. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing. Any bead/applesauce mixture should be used immediately and not stored for future use. Subdividing the contents of a verapamil hydrochloride extended-release capsule is not recommended.
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 mg 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) and 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.
Levetiracetam

Levetiracetam

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 one 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 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)].
Carisoprodol

Carisoprodol

The recommended dose of carisoprodol is 250 mg to 350 mg three times a day and at bedtime. The recommended maximum duration of carisoprodol use is up to two or three weeks.
Olanzapine

Olanzapine

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 mg 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 one week, since steady-state for olanzapine would not be achieved for approximately one 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 (5.14), 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

Pediatric dosing information in pediatric patients with schizophrenia is approved for Eli Lilly and Company’s olanzapine drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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 mg 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 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

Pediatric dosing information in pediatric patients with bipolar I disorder is approved for Eli Lilly and Company’s olanzapine drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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

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

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 mg to 12.5 mg and fluoxetine 20 mg to 50 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination in adult patients with a dose range of olanzapine 6 mg to 12 mg and fluoxetine 25 mg to 50 mg.

Safety and efficacy of olanzapine and fluoxetine in combination 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 olanzapine 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 Symbyax *** and the Combination of Olanzapine and Fluoxetine * Symbyax ** (olanzapine/fluoxetine HCl) is a fixed dose combination of olanzapine and fluoxetine. For Symbyax** (mg/day) Use in Combination Olanzapine(mg/day) Fluoxetine (mg/day)
3 mg olanzapine/25 mg fluoxetine

6 mg olanzapine/25 mg fluoxetine

12 mg olanzapine/25 mg fluoxetine

6 mg olanzapine/50 mg fluoxetine
12 mg olanzapine/50 mg fluoxetine
2.5

5

10 + 2.5

5
10 + 2.5
20

20

20

40+10
40+10
While there is no body of evidence to answer the question of how long a patient treated with olanzapine 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.

Safety of coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.

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

2.7 Olanzapine and Fluoxetine in Combination: Dosing in Special Populations

The starting dose of oral olanzapine 2.5 mg 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 and fluoxetine in combination have not been systematically studied in patients over 65 years of age or in patients < 18 years of age [see Warnings and Precautions (5.14), Drug Interactions (7), and Clinical Pharmacology (12.3)].
Loratadine

Loratadine

adults and children6 years and over 1 tablet daily; not morethan 1 tablet in 24 hours children under 6 years of age ask a doctor
consumers with liveror kidney disease
ask a doctor
Indomethacin

Indomethacin

Carefully consider the potential benefits and risks of indomethacin and other treatment options before deciding to use indomethacin. 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 indomethacin, the dose and frequency should be adjusted to suit an individual patient’s needs.

Indomethacin is available as 25 mg and 50 mg capsules.

Adverse reactions appear to correlate with the size of the dose of indomethacin in most patients but not all. Therefore, every effort should be made to determine the smallest effective dosage for the individual patient.

Pediatric Use

Indomethacin ordinarily should not be prescribed for pediatric patients 14 years of age and under (see WARNINGS).

Adult Use

Dosage Recommendations for Active Stages of the Following:

1. Moderate to severe rheumatoid arthritis including acute flares of chronic disease; moderate to severe ankylosing spondylitis; and moderate to severe osteoarthritis.

Suggested Dosage: Indomethacin capsules 25 mg b.i.d. or t.i.d. If this is well tolerated, increase the daily dosage by 25 mg or by 50 mg, if required by continuing symptoms, at weekly intervals until a satisfactory response is obtained or until a total daily dose of 150 mg to 200 mg is reached. DOSES ABOVE THIS AMOUNT GENERALLY DO NOT INCREASE THE EFFECTIVENESS OF THE DRUG.

In patients who have persistent night pain and/or morning stiffness, the giving of a large portion, up to a maximum of 100 mg, of the total daily dose at bedtime may be helpful in affording relief. The total daily dose should not exceed 200 mg. In acute flares of chronic rheumatoid arthritis, it may be necessary to increase the dosage by 25 mg or, if required, by 50 mg daily.

If minor adverse effects develop as the dosage is increased, reduce the dosage rapidly to a tolerated dose and OBSERVE THE PATIENT CLOSELY.

If severe adverse reactions occur, STOP THE DRUG. After the acute phase of the disease is under control, an attempt to reduce the daily dose should be made repeatedly until the patient is receiving the smallest effective dose or the drug is discontinued.

Careful instructions to, and observations of, the individual patient are essential to the prevention of serious, irreversible, including fatal, adverse reactions.

As advancing years appear to increase the possibility of adverse reactions, indomethacin should be used with greater care in the elderly (see PRECAUTIONS: Geriatric Use).

2. Acute painful shoulder (bursitis and/or tendinitis).

Initial Dose: 75 mg to 150 mg daily in 3 or 4 divided doses. The drug should be discontinued after the signs and symptoms of inflammation have been controlled for several days. The usual course of therapy is 7 to 14 days.

3. Acute gouty arthritis.

Suggested Dosage: Indomethacin capsules 50 mg t.i.d. until pain is tolerable. The dose should then be rapidly reduced to complete cessation of the drug. Definite relief of pain has been reported within 2 to 4 hours. Tenderness and heat usually subside in 24 to 36 hours, and swelling gradually disappears in 3 to 5 days.
Divalproex Sodium

Divalproex Sodium

2.1 Epilepsy

Divalproex sodium delayed-release capsules are administered orally. As divalproex sodium 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 capsules 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 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 capsules 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)]. 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 are 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 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 capsules should be initiated at the same daily dose and dosing schedule. After the patient is stabilized on divalproex sodium delayed-release capsules, a dosing schedule of 2 or 3 times a day may be elected in selected patients.

2.2 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 (5.13), 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 (5.7)].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.

Administration of Sprinkle Capsules

Divalproex sodium delayed-release capsules may be swallowed whole or may be administered by carefully opening the capsule and sprinkling the entire contents on a small amount (teaspoonful) of soft food such as applesauce or pudding. The drug/food mixture should be swallowed immediately (avoid chewing) and not stored for future use. Each capsule is oversized to allow ease of opening.
Zonisamide

Zonisamide

Zonisamide capsules are recommended as adjunctive therapy for the treatment of partial seizures in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established. Zonisamide capsules should be administered once or twice daily, using 25 mg, 50 mg or 100 mg capsules. Zonisamide capsules are given orally and can be taken with or without food. Capsules should be swallowed whole.

Adults Over Age 16

The prescriber should be aware that, because of the long half-life of zonisamide, up to 2 weeks may be required to achieve steady-state levels upon reaching a stable dose or following dosage adjustment. Although the regimen described below is one that has been shown to be tolerated, the prescriber may wish to prolong the duration of treatment at the lower doses in order to fully assess the effects of zonisamide at steady-state, noting that many of the side effects of zonisamide are more frequent at doses of 300 mg per day and above. Although there is some evidence of greater response at doses above 100 to 200 mg/day, the increase appears small and formal dose-response studies have not been conducted.

The initial dose of zonisamide capsules should be 100 mg daily. After 2 weeks, the dose may be increased to 200 mg/day for at least 2 weeks. It can be increased to 300 mg/day and 400 mg/day, with the dose stable for at least 2 weeks to achieve steady-state at each level. Evidence from controlled trials suggests that zonisamide capsule doses of 100 to 600 mg/day are effective, but there is no suggestion of increasing response above 400 mg/day (see CLINICAL PHARMACOLOGY: Clinical Studies). There is little experience with doses greater than 600 mg/day.

Patients with Renal or Hepatic Disease

Because zonisamide is metabolized in the liver and excreted by the kidneys, patients with renal or hepatic disease should be treated with caution, and might require slower titration and more frequent monitoring (see CLINICAL PHARMACOLOGY and PRECAUTIONS).
Amantadine Hydrochlorid...

Amantadine Hydrochloride

The dose of Amantadine Hydrochloride Capsules, USP may need reduction in patients with congestive heart failure, peripheral edema, orthostatic hypotension, or impaired renal function (see Dosage for Impaired Renal Function).

Dosage for Prophylaxis and Treatment of Uncomplicated Influenza A Virus Illness:

Adult: The adult daily dosage of Amantadine Hydrochloride Capsules, USP is 200 mg; two 100 mg capsules as a single daily dose. The daily dosage may be split into one capsule of 100 mg twice a day. If central nervous system effects develop in once-a-day dosage, a split dosage schedule may reduce such complaints. In persons 65 years of age or older, the daily dosage of Amantadine Hydrochloride Capsules, USP is 100 mg.

A 100 mg daily dose has also been shown in experimental challenge studies to be effective as prophylaxis in healthy adults who are not at high risk for influenza-related complications. However, it has not been demonstrated that a 100 mg daily dose is as effective as a 200 mg daily dose for prophylaxis, nor has the 100 mg daily dose been studied in the treatment of acute influenza illness. In recent clinical trials, the incidence of central nervous system (CNS) side effects associated with the 100 mg daily dose was at or near the level of placebo. The 100 mg dose is recommended for persons who have demonstrated intolerance to 200 mg of Amantadine Hydrochloride Capsules, USP daily because of CNS or other toxicities.

Pediatric Patients: 1 yr.-9 yrs. of age: The total daily dose should be calculated on the basis of 2 to 4 mg/lb/day (4.4 to 8.8 mg/kg/day), but not to exceed 150 mg per day.

9 yrs.-12 yrs. of age: The total daily dose is 200 mg given as one capsule of 100 mg twice a day. The 100 mg daily dose has not been studied in this pediatric population. Therefore, there are no data which demonstrate that this dose is as effective as or is safer than the 200 mg daily dose in this patient population.

Prophylactic dosing should be started in anticipation of an influenza A outbreak and before or after contact with individuals with influenza A virus respiratory tract illness.

Amantadine Hydrochloride Capsules, USP should be continued daily for at least 10 days following a known exposure. If Amantadine Hydrochloride Capsules, USP are used chemoprophylactically in conjunction with inactivated influenza A virus vaccine until protective antibody responses develop, then it should be administered for 2 to 4 weeks after the vaccine has been given. When inactivated influenza A virus vaccine is unavailable or contraindicated, Amantadine Hydrochloride Capsules, USP should be administered for the duration of known influenza A in the community because of repeated and unknown exposure.

Treatment of influenza A virus illness should be started as soon as possible, preferably within 24 to 48 hours after onset of signs and symptoms, and should be continued for 24 to 48 hours after the disappearance of signs and symptoms.

Dosage for Parkinsonism:

Adult: The usual dose of Amantadine Hydrochloride Capsules, USP is 100 mg twice a day when used alone. Amantadine Hydrochloride Capsules, USP have an onset of action usually within 48 hours.

The initial dose of Amantadine Hydrochloride Capsules, USP is 100 mg daily for patients with serious associated medical illnesses or who are receiving high doses of other antiparkinson drugs. After one to several weeks at 100 mg once daily, the dose may be increased to 100 mg twice daily, if necessary.

Occasionally, patients whose responses are not optimal with Amantadine Hydrochloride Capsules, USP at 200 mg daily may benefit from an increase up to 400 mg daily in divided doses. However, such patients should be supervised closely by their physicians.

Patients initially deriving benefit from Amantadine Hydrochloride Capsules, USP not uncommonly experience a fall-off of effectiveness after a few months. Benefit may be regained by increasing the dose to 300 mg daily. Alternatively, temporary discontinuation of Amantadine Hydrochloride Capsules, USP for several weeks, followed by reinitiation of the drug, may result in regaining benefit in some patients. A decision to use other antiparkinson drugs may be necessary.

Dosage for Concomitant Therapy: Some patients who do not respond to anticholinergic antiparkinson drugs may respond to Amantadine Hydrochloride Capsules, USP. When Amantadine Hydrochloride Capsules, USP or anticholinergic antiparkinson drugs are each used with marginal benefit, concomitant use may produce additional benefit.

When Amantadine Hydrochloride Capsules, USP and levodopa are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Amantadine Hydrochloride Capsules, USP should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal benefit.

When Amantadine Hydrochloride Capsules, USP are added to optimal well-tolerated doses of levodopa, additional benefit may result, including smoothing out the fluctuations in improvement which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of Amantadine Hydrochloride Capsules, USP.

Dosage for Drug-Induced Extrapyramidal Reactions:

Adult: The usual dose of Amantadine Hydrochloride Capsules, USP is 100 mg twice a day. Occasionally, patients whose responses are not optimal with Amantadine Hydrochloride Capsules, USP at 200 mg daily may benefit from an increase up to 300 mg daily in divided doses.

Dosage for Impaired Renal Function:

Depending upon creatinine clearance, the following dosage adjustments are recommended:
CREATININE CLEARANCE AMANTADINE HYDROCHLORIDE (mL/min/1.73 m2) CAPSULES, USP DOSAGE 30-50 200 mg 1st day and 100 mg each day thereafter 15-29 200 mg 1st day followed by 100 mg on alternate days <15 200 mg every 7 days
The recommended dosage for patients on hemodialysis is 200 mg every 7 days.
Alprazolam

Alprazolam

Essential Hypertension

The dose of verapamil hydrochloride extended-release tablets should be individualized by titration and the drug should be administered with food. Initiate therapy with 180 mg of verapamil hydrochloride extended-release tablets given in the morning. Lower initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (e.g., the elderly or small people). Upward titration should be based on therapeutic efficacy and safety evaluated weekly and approximately 24 hours after the previous dose. The antihypertensive effects of verapamil hydrochloride extended-release tablets are evident within the first week of therapy.

If adequate response is not obtained with 180 mg of verapamil hydrochloride extended-release tablets, the dose may be titrated upward in the following manner:
• 240 mg each morning, • 180 mg each morning plus 180 mg each evening; or 240 mg each morning plus 120 mg each evening, • 240 mg every 12 hours.
When switching from verapamil hydrochloride immediate-release tablets to verapamil hydrochloride extended-release tablets, the total daily dose in milligrams may remain the same.
Mucinex Sinus-max Sever...

Mucinex Sinus-max Severe Congestion Relief

• do not take more than directed unless advised by your doctor • adults and children 17 years of age and older: • stir and dissolve the contents of one pouch (17 g) into any 4 to 8 ounces of beverage (cold, hot or room temperature) then drink • use once a day • use no more than 7 days • children 16 years of age or under: ask a doctor
Valproic Acid

Valproic Acid

THE CAPSULES SHOULD BE SWALLOWED WITHOUT CHEWING TO AVOID LOCAL IRRITATION OF THE MOUTH AND THROAT.

Valproic Acid Capsules, USP are administered orally. Valproic Acid Capsules, USP 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 Valproic Acid Capsules, USP dosage is titrated upward, concentrations of phenobarbital, carbamazepine, and/or phenytoin may be affected (see PRECAUTIONS -Drug Interactions).

Complex Partial Seizures

For adults and children 10 years of age or older.

Monotherapy (Initial Therapy)

Valproic Acid Capsules, USP 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 µg/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 µg/mL in females and 135 µg/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 -100 µg/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 Valproic Acid Capsules, USP 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

Valproic Acid Capsules, USP 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 µg/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 divalproex sodium tablets, no adjustment of carbamazepine or phenytoin dosage was needed (see CLINICAL STUDIES). However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs (see Drug Interactions), periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy (see PRECAUTIONS- Drug Interactions).

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 µg/mL. Some patients may be controlled with lower or higher serum concentrations (see CLINICAL PHARMACOLOGY).

As the Valproic Acid Capsules, USP dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected (see PRECAUTIONS).

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.

The following table is a guide for the initial daily dose of Valproic Acid Capsules, USP (15 mg/kg/day):
Weight Number of Capsules (Kg) (Lb) Total DailyDose (mg) Dose 1 Dose 2 Dose 3 10-24.9 22-54.9 250 0 0 1 25-39.9 55-87.9 500 1 0 1 40-59.9 88-131.9 750 1 1 1 60-74.9 132-164.9 1,000 1 1 2 75-89.9 165-197.9 1,250 2 1 2
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 events. 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).

Dose-Related Adverse Events

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 µg/mL (females) or ≥135 µg/mL (males) (see PRECAUTIONS). 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.
Sertraline Hydrochlorid...

Sertraline Hydrochloride

Sertraline tablets are available with each tablet containing sertraline hydrochloride equivalent to 25 mg, 50 mg or 100 mg of sertraline.

Initial Treatment

Dosage for Adults

Major Depressive Disorder and Obsessive-Compulsive Disorder

Sertraline tablet treatment should be administered at a dose of 50 mg once daily.

Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder

Sertraline tablet 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 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 tablets, dose changes should not occur at intervals of less than one week.

Premenstrual Dysphoric Disorder

Sertraline tablet 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 PHARMACOLOGY: Clinical Trials). 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 3 days should be utilized at the beginning of each luteal phase dosing period.

Sertraline tablets should be administered once daily, either in the morning or evening.

Dosage for Pediatric Population (Children and Adolescents)

Obsessive-Compulsive Disorder

Sertraline tablet 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 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, dose changes should not occur at intervals of less than one week.

Sertraline 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 tablets 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 PHARMACOLOGY: Clinical Trials). It is not known whether the dose of sertraline 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 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 PHARMACOLOGY: Clinical Trials). It is not known whether the dose of sertraline 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 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 PHARMACOLOGY: Clinical Trials). 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 tablets for periods of up to 28 weeks in patients with OCD and panic disorder who have responded while taking sertraline 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 PHARMACOLOGY: Clinical Trials). It is not known whether the dose of sertraline 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 in long-term use, that is, for more than three 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 vs. 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 Patients to or from a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with sertraline tablets. In addition, at least 14 days should be allowed after stopping sertraline tablets before starting an MAOI (see CONTRAINDICATIONS and 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 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 during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering sertraline in the third trimester.

Discontinuation of Treatment with Sertraline

Symptoms associated with discontinuation of sertraline 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.
Galantamine

Galantamine

2.2 Galantamine Tablets

The dosage of galantamine tablets shown to be effective in controlled clinical trials is 16-32 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 16-24 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.

2.3Hepatic Impairment

Galantamine plasma concentrations may be increased in patients with moderate to severe hepatic impairment. In patients with moderately impaired hepatic function (Child-Pugh score of 7 to 9), the total daily 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.

2.4Renal Impairment

For patients with moderate renal impairment the dosage should generally not exceed 16 mg/day. In patients with severe renal impairment (creatinine clearance < 9 mL/min), the use of galantamine tablets is not recommended.
Metoprolol Tartrate

Metoprolol Tartrate

Hypertension

Individualize the dosage of metoprolol tartrate tablets. Metoprolol tartrate tablets should be taken with or immediately following meals.

The usual initial dosage of metoprolol tartrate tablets is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. Increase the dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after one week of therapy. The effective dosage range of metoprolol tartrate tablets is 100 mg to 450 mg per day. Dosages above 450 mg per day have not been studied. While once daily dosing is effective and can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period, and larger or more frequent daily doses may be required. This can be evaluated by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. Beta1 selectivity diminishes as the dose of metoprolol is increased.

Angina Pectoris

The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately following meals.

The usual initial dosage of metoprolol tartrate tablets is 100 mg daily, given in two divided doses. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range of metoprolol tartrate tablets is 100 mg to 400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, gradually decrease the dosage over a period of 1 to 2 weeks (see WARNINGS).

Myocardial Infarction

Early Treatment

During the early phase of definite or suspected acute myocardial infarction, initiate treatment with metoprolol tartrate tablets as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized.

Begin treatment in this early phase with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; give the injections at approximately 2 minute intervals. During the intravenous administration of metoprolol, monitor blood pressure, heart rate, and electrocardiogram.

In patients who tolerate the full intravenous dose (15 mg), initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose and continue for 48 hours. Thereafter, the maintenance dosage is 100 mg twice daily (see Late Treatment below).

Start patients who appear not to tolerate the full intravenous dose on metoprolol tartrate tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. In patients with severe intolerance, discontinue metoprolol tartrate tablets (see WARNINGS).

Late Treatment

Start patients with contraindications to treatment during the early phase of suspected or definite myocardial infarction, patients who appear not to tolerate the full early treatment, and patients in whom the physician wishes to delay therapy for any other reason on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Continue therapy for at least 3 months. Although the efficacy of metoprolol beyond 3 months has not been conclusively established, data from studies with other beta-blockers suggest that treatment should be continued for 1 to 3 years.

Special Populations

Pediatric Patients

No pediatric studies have been performed. The safety and efficacy of metoprolol in pediatric patients have not been established.

Renal Impairment

No dose adjustment of metoprolol tartrate tablets is required in patients with renal impairment.

Hepatic Impairment

Metoprolol blood levels are likely to increase substantially in patients with hepatic impairment. Therefore, metoprolol tartrate tablets should be initiated at low doses with cautious gradual dose titration according to clinical response.

Geriatric Patients (> 65 Years)

In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Method of Administration

For oral treatment, the tablets should be swallowed unchewed with a glass of water. Metoprolol tartrate tablets should always be taken in standardized relation with meals. If the physician asks the patient to take metoprolol tartrate tablets either before breakfast or with breakfast, then the patient should continue taking metoprolol tartrate tablets with the same schedule during the course of therapy.
Metoprolol Succinate

Metoprolol Succinate

Metoprolol succinate is an extended-release tablet intended for once daily administration. For treatment of hypertension and angina, when switching from immediate-release metoprolol to metoprolol succinate extended-release tablets, use the same total daily dose of metoprolol succinate extended-release tablets. Individualize the dosage of metoprolol succinate extended-release tablets. Titration may be needed in some patients.

Metoprolol succinate extended-release tablets are scored and can be divided; however, do not crush or chew the whole or half tablet.

2.1Hypertension

Adults

The usual initial dosage is 25 mg to 100 mg daily in a single dose. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after one week of therapy. Dosages above 400 mg per day have not been studied.

Pediatric Hypertensive Patients ≥ 6 Years of Age

A pediatric clinical hypertension study in patients 6 to 16 years of age did not meet its primary endpoint (dose-response for reduction in SBP); however some other endpoints demonstrated effectiveness [see Use in Specific Populations (8.4)]. If selected for treatment, the recommended starting dose of metoprolol succinate extended-release tablets is 1 mg/kg once daily, but the maximum initial dose should not exceed 50 mg once daily. Dosage should be adjusted according to blood pressure response. Doses above 2 mg/kg (or in excess of 200 mg) once daily have not been studied in pediatric patients [see Clinical Pharmacology (12.3)].

Metoprolol succinate extended-release tablets are not recommended in pediatric patients < 6 years of age [see Use in Specific Populations (8.4)].

2.2Angina Pectoris

Individualize the dosage of metoprolol succinate extended-release tablets. The usual initial dosage is 100 mg daily, given in a single dose. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is a pronounced slowing of the heart rate. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, reduce the dosage gradually over a period of 1 to 2 weeks [see Warnings and Precautions (5)].

2.3Heart Failure

Dosage must be individualized and closely monitored during up-titration. Prior to initiation of metoprolol succinate extended-release tablets, stabilize the dose of other heart failure drug therapy. The recommended starting dose of metoprolol succinate extended-release tablets is 25 mg once daily for 2 weeks in patients with NYHA Class II heart failure and 12.5 mg once daily in patients with more severe heart failure. Double the dose every 2 weeks to the highest dosage level tolerated by the patient or up to 200 mg of metoprolol succinate extended-release tablets. Initial difficulty with titration should not preclude later attempts to introduce metoprolol succinate extended-release tablets. If patients experience symptomatic bradycardia, reduce the dose of metoprolol succinate extended-release tablets. If transient worsening of heart failure occurs, consider treating with increased doses of diuretics, lowering the dose of metoprolol succinate extended-release tablets or temporarily discontinuing it. The dose of metoprolol succinate extended-release tablets should not be increased until symptoms of worsening heart failure have been stabilized.
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 mg 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/1.73m2, 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 are not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2 [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 6 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 one 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)].
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 mg to 2 mg

4 mg to 8 mg

4 mg to 16 mg

Schizophrenia: adolescents (2.2)

0.5 mg

0.5 mg to 1 mg

3 mg

1 mg to 6 mg

Bipolar mania: adults (2.2)

2 mg to 3 mg

1 mg

1 mg to 6 mg

1 mg to 6 mg

Bipolar mania: children and adolescents (2.2)

0.5 mg

0.5 mg to 1mg

1 mg to 2.5 mg

1 mg 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 weight greater than or equal to 20 kg)

0.5 mg 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/day. May increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg/day, as tolerated, to a recommended dose of 4 to 8 mg/day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 to 16 mg/day. However, doses above 6 mg/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/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/day, as tolerated, to a recommended dose of 3 mg/day. Although efficacy has been demonstrated in studies of adolescent patients with schizophrenia at doses between 1 and 6 mg/day, no additional benefit was observed above 3 mg/day, and higher doses were associated with more adverse events. Doses higher than 6 mg/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 2 to 8 mg/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 Dose

Adults

The initial dose range is 2 to 3 mg/day. The dose may be adjusted at intervals of 24 hours or greater, in increments of 1 mg/day. The effective dose range is 1 to 6 mg/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 to 6 mg/day [see Clinical Studies (14.2, 14.3)]. Risperidone tablet doses higher than 6 mg/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 or 1 mg/day, as tolerated, to the recommended target dose of 1 to 2.5 mg/day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 and 6 mg/day, no additional benefit was observed above 2.5 mg/day, and higher doses were associated with more adverse events. Doses higher than 6 mg/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 reevaluate 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/day. For patients with body weight greater than or equal to 20 kg, initiate dosing at 0.5 mg/day. After a minimum of 4 days, the dose may be increased to the recommended dose of 0.5 mg/day for patients less than 20 kg and 1 mg/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/day for patients less than 20 kg, or increments of 0.5 mg/day for patients greater than or equal to 20 kg. The effective dose range is 0.5 to 3 mg/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 reevaluate 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 coadministered 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 tablet dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1)]. Similar effect may be expected with coadministration of risperidone tablets with other enzyme inducers (e.g., phenytoin, rifampin and phenobarbital).

When fluoxetine or paroxetine are coadministered with risperidone tablets, the dose of risperidone tablets should be reduced. The risperidone tablet dose should not exceed 8 mg/day in adults when coadministered with these drugs. When initiating therapy, risperidone tablets should be titrated slowly. It may be necessary to increase the risperidone tablet dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1)].
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 mg to 2 mg

4 mg to 8 mg

4 mg to 16 mg

Schizophrenia- adolescents (2.1)

0.5 mg

0.5 mg to 1 mg

3 mg

1 mg to 6 mg

Bipolar mania- adults (2.2)

2 mg to 3 mg

1 mg

1 mg to 6 mg

1 mg to 6 mg

Bipolar mania- children and adolescents (2.2)

0.5 mg

0.5 mg to 1 mg

1 mg to 2.5 mg

1 mg 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 weight greater than or equal to 20 kg)

0.5 mg 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 orally disintegrating 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 mg to 2 mg per day, as tolerated, to a recommended dose of 4 mg 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 orally disintegrating tablets, the effectiveness of risperidone 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 orally disintegrating 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 orally disintegrating tablets, or treating patients with concomitant antipsychotics.

2.2 Bipolar Mania

Usual Dose

Adults

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 orally disintegrating tablet 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 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 orally disintegrating 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 orally disintegrating tablets in such longer term treatment (i.e., beyond 3 weeks). The physician who elects to use risperidone orally disintegrating tablets for extended periods should periodically reevaluate 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 orally disintegrating tablets should be individualized according to the response and tolerability of the patient. The total daily dose of risperidone orally disintegrating 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 4 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 orally disintegrating tablets for extended periods should periodically reevaluate 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 orally disintegrating tablets are coadministered with enzyme inducers (e.g., carbamazepine), the dose of risperidone should be increased up to double the patient’s usual dose. It may be necessary to decrease the risperidone dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1)]. Similar effect may be expected with coadministration of risperidone orally disintegrating tablets with other enzyme inducers (e.g., phenytoin, rifampin and phenobarbital).

When fluoxetine or paroxetine is coadministered with risperidone orally disintegrating tablets, the dose of risperidone should be reduced. The risperidone dose should not exceed 8 mg per day in adults when coadministered with these drugs. When initiating therapy, risperidone orally disintegrating tablets should be titrated slowly. It may be necessary to increase the risperidone dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1)].

2.7 Directions for Use of Risperidone Orally Disintegrating Tablets

Tablet Accessing

Risperidone Orally Disintegrating Tablets 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg

Risperidone orally disintegrating tablets 0.5 mg is supplied in bottles containing 28 and 30 tablets, and risperidone orally disintegrating tablets, 0.25 mg, 1 mg, 2 mg, 3 mg and 4 mg are supplied in bottles containing 28 tablets.

Tablet Administration

Using dry hands, remove the tablet from the bottle and immediately place the entire risperidone orally disintegrating tablet on the tongue. The risperidone orally disintegrating tablet should be consumed immediately. Risperidone orally disintegrating tablets disintegrate in the mouth within seconds and can be swallowed subsequently with or without liquid. Patients should not attempt to split or to chew the tablet.
Venlafaxine Hydrochlori...

Venlafaxine Hydrochloride

Initial Treatment

The recommended starting dose for venlafaxine tablets is 75 mg/day, administered in two or three divided doses, taken with food. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided doses (see PRECAUTIONS: General: Use in Patients with Concomitant Illness).

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to venlafaxine tablets, 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 tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering venlafaxine tablets in the third trimester.

Dosage for 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 to 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.

Dosage for 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 to normals (see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose be reduced by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% in patients undergoing hemodialysis. Since there was much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Dosage for Elderly Patients

No dose adjustment is recommended for elderly patients on the basis of age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

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. 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 mg/day, 150 mg/day, 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 tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine tablets 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). Based on these limited data, it is not known whether or not the dose of venlafaxine tablets/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.

Discontinuing Venlafaxine Tablets

Symptoms associated with discontinuation of venlafaxine tablets, 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.
Ranitidine Hydrochlorid...

Ranitidine Hydrochloride

Active Duodenal Ulcer

The current recommended adult oral dosage of ranitidine for duodenal ulcer is 150 mg twice daily. An alternative dosage of 300 mg 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 PHARMACOLOGY: Clinical Trials: Active Duodenal Ulcer). Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in US 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 at bedtime.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome)

The current recommended adult oral dosage is 150 mg twice a day. 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 twice a day.

Maintenance of Healing of Gastric Ulcers

The current recommended adult oral dosage is 150 mg at bedtime.

GERD

The current recommended adult oral dosage is 150 mg twice a day.

Erosive Esophagitis

The current recommended adult oral dosage is 150 mg four times a day.

Maintenance of Healing of Erosive Esophagitis

The current recommended adult oral dosage is 150 mg twice a day.

Pediatric Use

The safety and effectiveness of ranitidine has 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 per day, usually given as two 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 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).
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 nine or fewer recurrences per year, an alternative dose is 500 mg once daily.

In HIV-infected patients with a CD4+ cell count ≥ 100 cells/mm3, 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 nine 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 three 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 (five valacyclovir tablets for 25 mg/mL suspension; ten 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 three 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 m2.
Table 1. Valacyclovir Dosage Recommendations for Adults with Renal Impairment
Indications

Normal Dosage Regimen(Creatinine Clearance ≥ 50 mL/min)

Creatinine Clearance (mL/min)

30 to 49

10 to 29

< 10

Cold sores (Herpes labialis) Do not exceed 1 day of treatment.

Two 2 gram doses taken 12 hours apart

Two 1 gram doses taken 12 hours apart

Two 500 mg doses taken 12 hours apart

500 mg single dose

Genital herpes:    Initial episode

1 gram every

12 hours

no reduction

1 gram every

24 hours

500 mg every

24 hours

Genital herpes:    Recurrent episode

500 mg every

12 hours

no reduction

500 mg every

24 hours

500 mg every

24 hours

Genital herpes:     Suppressive Therapy

      Immunocompetent patients

1 gram every 24 hours

no reduction

500 mg every 24 hours

500 mg every 24 hours

      Alternate dose for immunocompetent patients with ≤ 9 recurrences/year

500 mg every 24 hours

no reduction

500 mg every 48 hours

500 mg every 48 hours

      HIV-infected patients

500 mg every 12 hours

no reduction

500 mg every 24 hours

500 mg every 24 hours

Herpes zoster

1 gram every

8 hours

1 gram every

12 hours

1 gram every

24 hours

500 mg every

24 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.
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 strains [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 strains [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 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 levofloxacin therapy should only be used when the benefit outweighs the risk. 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 and ≥ 6 months of age Þß Pediatric patients < 50 kg and ≥ 6 months of ageÞß 500 mgsee Table 2 below (2.2)
60ß
60ß

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 * Due to Bacillus anthracis [see Indications and Usage (1.13)] † 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 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 therapy should only be used when the benefit outweighs the risk. Type of Infection* Dose Freq. Once Every Duration†
Inhalational Anthrax (post-exposure)‡§      Pediatric patients > 50 kg and ≥ 6 months of age

    Pediatric patients < 50 kg and ≥ 6 months of age

  500 mg

8 mg/kg(not to exceed
250 mg per dose)
24 hr

12 hr

60 days§

60 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 in Normal Renal Function Every 24 hours Creatinine Clearance 20 to 49 mL/min
Creatinine Clearance
10 to 19 mL/min Hemodialysis or Chronic Ambulatory Peritoneal 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 2 hours before or 2 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)].
Paroxetine Hydrochlorid...

Paroxetine Hydrochloride

Major Depressive Disorder

Usual Initial Dosage

Paroxetine hydrochloride extended-release tablets should be administered as a single daily dose, usually in the morning, with or without food. The recommended initial dose is 25 mg/day. Patients were dosed in a range of 25 mg to 62.5 mg/day in the clinical trials demonstrating the effectiveness of paroxetine hydrochloride extended-release tablets in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, the full effect may be delayed. Some patients not responding to a 25 mg dose may benefit from dose increases, in 12.5 mg/day increments, up to a maximum of 62.5 mg/day. Dose changes should occur at intervals of at least one week.

Patients should be cautioned that paroxetine hydrochloride extended-release tablets should not be chewed or crushed and should be swallowed whole.

Maintenance Therapy

There is no body of evidence available to answer the question of how long the patient treated with paroxetine hydrochloride extended-release tablets should remain on it. It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Whether the dose of an antidepressant needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Systematic evaluation of the efficacy of immediate-release paroxetine hydrochloride has shown that efficacy is maintained for periods of up to one year with doses that averaged about 30 mg, which corresponds to a 37.5 mg dose of paroxetine hydrochloride extended-release tablets, based on relative bioavailability considerations (see CLINICAL PHARMACOLOGY).

Panic Disorder

Usual Initial Dosage

Paroxetine hydrochloride extended-release tablets should be administered as a single daily dose, usually in the morning. Patients should be started on 12.5 mg/day. Dose changes should occur in 12.5 mg/day increments and at intervals of at least one week. Patients were dosed in a range of 12.5 to 75 mg/day in the clinical trials demonstrating the effectiveness of paroxetine hydrochloride extended-release tablets. The maximum dosage should not exceed 75 mg/day.

Patients should be cautioned that paroxetine hydrochloride extended-release tablets should not be chewed or crushed and should be swallowed whole.

Maintenance Therapy

Long-term maintenance of efficacy with the immediate-release formulation of paroxetine was demonstrated in a 3 month relapse prevention trial. In this trial, patients with panic disorder assigned to immediate-release paroxetine demonstrated a lower relapse rate compared to patients on placebo. Panic disorder is a chronic condition and it is reasonable to consider continuation for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment.

Social Anxiety Disorder

Usual Initial Dosage

Paroxetine hydrochloride extended-release tablets should be administered as a single daily dose, usually in the morning, with or without food. The recommended initial dose is 12.5 mg/day. Patients were dosed in a range of 12.5 mg to 37.5 mg/day in the clinical trial demonstrating the effectiveness of paroxetine hydrochloride extended-release tablets in the treatment of social anxiety disorder. If the dose is increased, this should occur at intervals of at least one week, in increments of 12.5 mg/day, up to a maximum of 37.5 mg/day.

Patients should be cautioned that paroxetine hydrochloride extended-release tablets should not be chewed or crushed and should be swallowed whole.

Maintenance Therapy

There is no body of evidence available to answer the question of how long the patient treated with paroxetine hydrochloride extended-release tablets should remain on it. Although the efficacy of paroxetine hydrochloride extended-release tablets beyond 12 weeks of dosing has not been demonstrated in controlled clinical trials, social anxiety disorder is recognized as a chronic condition and it is reasonable to consider continuation of treatment for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment.

Premenstrual Dysphoric Disorder

Usual Initial Dosage

Paroxetine hydrochloride extended-release tablets should be administered as a single daily dose, usually in the morning, with or without food. Paroxetine hydrochloride extended-release tablets may be administered either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment. The recommended initial dose is 12.5 mg/day. In clinical trials, both 12.5 mg/day and 25 mg/day were shown to be effective. Dose changes should occur at intervals of at least one week.

Patients should be cautioned that paroxetine hydrochloride extended-release tablets should not be chewed or crushed and should be swallowed whole.

Maintenance/Continuation Therapy

The effectiveness of paroxetine hydrochloride extended-release tablets for a period exceeding three menstrual cycles has not been systematically evaluated in controlled trials. However, women commonly report that symptoms worsen with age until relieved by the onset of menopause. Therefore, it is reasonable to consider continuation of a responding patient. Patients should be periodically reassessed to determine the need for continued treatment.

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to paroxetine hydrochloride extended-release tablets and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding (see WARNINGS: Usage in Pregnancy). When treating pregnant women with paroxetine during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering paroxetine in the third trimester.

Dosage for Elderly or Debilitated Patients and Patients with Severe Renal or Hepatic Impairment

The recommended initial dose of paroxetine hydrochloride extended-release tablets is 12.5 mg/day for elderly patients, debilitated patients and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 50 mg/day.

Switching Patients to or From a Monoamine Oxidase Inhibitor Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with paroxetine hydrochloride extended-release tablets. Conversely, at least 14 days should be allowed after stopping paroxetine hydrochloride extended-release tablets before starting an MAOI.

Use of Paroxetine Hydrochloride Extended-release Tablets with Reversible MAOIs Such as Linezolid or Methylene Blue

Do not start paroxetine hydrochloride extended-release tablets in a patient who is being treated with linezolid or methylene blue because there is increased risk of serotonin syndrome or NMS-like reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered (see CONTRAINDICATIONS). In some cases, a patient receiving therapy with paroxetine hydrochloride extended-release tablets may require urgent treatment with linezolid or methylene blue. If acceptable alternatives to linezolid or methylene blue treatment are not available and the potential benefits of linezolid or methylene blue treatment are judged to outweigh the risks of serotonin syndrome or NMS-like reactions in a particular patient, paroxetine hydrochloride extended-release tablets should be stopped promptly, and linezolid or methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome or NMS-like reactions for 2 weeks or until 24 hours after the last dose of linezolid or methylene blue, whichever comes first. Therapy with paroxetine hydrochloride extended-release tablets may be resumed 24 hours after the last dose of linezolid or methylene blue (see WARNINGS).

Discontinuation of Treatment with Paroxetine Hydrochloride Extended-Release Tablets

Symptoms associated with discontinuation of immediate-release paroxetine hydrochloride or paroxetine hydrochloride extended-release tablets have been reported (see PRECAUTIONS: General: Discontinuation of Treatment with Paroxetine Hydrochloride Extended-release Tablets). Patients should be monitored for these symptoms when discontinuing treatment, regardless of the indication for which paroxetine hydrochloride extended-release tablets are being prescribed. 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.
Proderm

Proderm

Shake can well and hold approximately 12 inches from area to betreated, press valve and coat rapidly. Apply three times daily to areas prone to or exhibiting evidence oftissue breakdown. PRODERM serves as its own protective barrier; therefore, additionalbandaging is not required.
Ondansetron

Ondansetron

Prevention of Nausea and Vomiting Associated with Highly Emetogenic Cancer Chemotherapy

The recommended adult oral dosage of ondansetron hydrochloride 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 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 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 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 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 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 Use

There is no experience with the use of ondansetron tablets 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 16 mg given as two 8 mg ondansetron tablets one hour before induction of anesthesia.

Pediatric Use

There is no experience with the use of ondansetron tablets 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.
Atorvastatin Calcium

Atorvastatin Calcium

2.1 Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

The recommended starting dose of atorvastatin calcium tablets is 10 mg or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin calcium tablets is 10 mg to 80 mg once daily. Atorvastatin calcium tablets can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin calcium tablets should be individualized according to patient characteristics such as goal of therapy and response (see current NCEP Guidelines). After initiation and/or upon titration of atorvastatin calcium tablets, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

2.2 Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 Years of Age)

The recommended starting dose of atorvastatin calcium tablets is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy [see current NCEP Pediatric Panel Guidelines, Clinical Pharmacology (12) and Indications and Usage (1.2)]. Adjustments should be made at intervals of 4 weeks or more.

2.3 Homozygous Familial Hypercholesterolemia

The dosage of atorvastatin calcium tablets in patients with homozygous FH is 10 mg to 80 mg daily. Atorvastatin calcium 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.

2.4 Concomitant Lipid-lowering Therapy

Atorvastatin calcium tablets may be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].

2.5 Dosage in Patients with Renal Impairment

Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin calcium tablets; thus, dosage adjustment in patients with renal dysfunction is not necessary [see Warnings and Precautions, Skeletal Muscle (5.1), Clinical Pharmacology, Pharmacokinetics (12.3)].

2.6 Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole or Certain Protease Inhibitors

In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), therapy with atorvastatin calcium tablets should be avoided. In patients with HIV taking lopinavir plus ritonavir, caution should be used when prescribing atorvastatin calcium tablets and the lowest dose necessary employed. In patients taking clarithromycin, itraconazole or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, therapy with atorvastatin calcium tablets should be limited to 20 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed. In patients with HIV taking nelfinavir, therapy with atorvastatin calcium tablets should be limited to 40 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].
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.
Methotrexate

Methotrexate

Neoplastic Diseases

Oral administration in tablet form is often preferred when low doses are being administered since absorption is rapid and effective serum levels are obtained.

Choriocarcinoma and Similar Trophoblastic Diseases

Methotrexate is administered orally or intramuscularly in doses of 15 mg to 30 mg daily for a 5-day course. Such courses are usually repeated for 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside. The effectiveness of therapy is ordinarily evaluated by 24 hour quantitative analysis of urinary chorionic gonadotropin (hCG), which should return to normal or less than 50 IU/24 hr usually after the third or fourth course and usually be followed by a complete resolution of measurable lesions in 4 to 6 weeks. One to two courses of methotrexate after normalization of hCG is usually recommended. Before each course of the drug careful clinical assessment is essential. Cyclic combination therapy of methotrexate with other antitumor drugs has been reported as being useful.

Since hydatidiform mole may precede choriocarcinoma, prophylactic chemotherapy with methotrexate has been recommended.

Chorioadenoma destruens is considered to be an invasive form of hydatidiform mole. Methotrexate is administered in these disease states in doses similar to those recommended for choriocarcinoma.

Leukemia

Acute lymphoblastic leukemia in pediatric patients and young adolescents is the most responsive to present day chemotherapy. In young adults and older patients, clinical remission is more difficult to obtain and early relapse is more common.

Methotrexate alone or in combination with steroids was used initially for induction of remission in acute lymphoblastic leukemias. More recently corticosteroid therapy, in combination with other antileukemic drugs or in cyclic combinations with methotrexate included, has appeared to produce rapid and effective remissions. When used for induction, methotrexate in doses of 3.3 mg/m2 in combination with 60 mg/m2 of prednisone, given daily, produced remissions in 50% of patients treated, usually within a period of 4 to 6 weeks. Methotrexate in combination with other agents appears to be the drug of choice for securing maintenance of drug-induced remissions. When remission is achieved and supportive care has produced general clinical improvement, maintenance therapy is initiated, as follows: Methotrexate is administered 2 times weekly either by mouth or intramuscularly in total weekly doses of 30 mg/m2. It has also been given in doses of 2.5 mg/kg intravenously every 14 days. If and when relapse does occur, reinduction of remission can again usually be obtained by repeating the initial induction regimen.

A variety of combination chemotherapy regimens have been used for both induction and maintenance therapy in acute lymphoblastic leukemia. The physician should be familiar with the new advances in antileukemic therapy.

Lymphomas

In Burkitt’s tumor, Stages I-II, methotrexate has produced prolonged remissions in some cases. Recommended dosage is 10 to 25 mg/day orally for 4 to 8 days. In Stage III, methotrexate is commonly given concomitantly with other antitumor agents. Treatment in all stages usually consists of several courses of the drug interposed with 7 to 10 day rest periods. Lymphosarcomas in Stage III may respond to combined drug therapy with methotrexate given in doses of 0.625 to 2.5 mg/kg daily.

Mycosis Fungoides (cutaneous T cell lymphoma)

Therapy with methotrexate as a single agent appears to produce clinical responses in up to 50% of patients treated. Dosage in early stages is usually 5 mg to 50 mg once weekly. Dose reduction or cessation is guided by patient response and hematologic monitoring. Methotrexate has also been administered twice weekly in doses ranging from 15 mg to 37.5 mg in patients who have responded poorly to weekly therapy.

Psoriasis, Rheumatoid Arthritis, and Juvenile Rheumatoid Arthritis

Adult Rheumatoid Arthritis

Recommended Starting Dosage Schedules
1. Single oral doses of 7.5 mg once weekly. 2. Divided oral dosages of 2.5 mg at 12 hour intervals for three doses given as a course once weekly.
Polyarticular-Course Juvenile Rheumatoid Arthritis

The recommended starting dose is 10 mg/m2 given once weekly.

For either adult RA or polyarticular-course JRA dosages may be adjusted gradually to achieve an optimal response. Limited experience shows a significant increase in the incidence and severity of serious toxic reactions, especially bone marrow suppression, at doses greater than 20 mg/wk in adults. Although there is experience with doses up to 30 mg/m2/wk in children, there are too few published data to assess how doses over 20 mg/m2/wk might affect the risk of serious toxicity in children. Experience does suggest, however, that children receiving 20 to 30 mg/m2/wk (0.65 to 1.0 mg/kg/wk) may have better absorption and fewer gastrointestinal side effects if methotrexate is administered either intramuscularly or subcutaneously.

Therapeutic response usually begins within 3 to 6 weeks and the patient may continue to improve for another 12 weeks or more.

The optimal duration of therapy is unknown. Limited data available from long-term studies in adults indicate that the initial clinical improvement is maintained for at least 2 years with continued therapy. When methotrexate is discontinued, the arthritis usually worsens within 3 to 6 weeks.

The patient should be fully informed of the risks involved and should be under constant supervision of the physician. (See PRECAUTIONS: Information for Patients.) Assessment of hematologic, hepatic, renal, and pulmonary function should be made by history, physical examination, and laboratory tests before beginning, periodically during, and before reinstituting methotrexate therapy. (See PRECAUTIONS.) Appropriate steps should be taken to avoid conception during methotrexate therapy. (See PRECAUTIONS and CONTRAINDICATIONS.)

All schedules should be continually tailored to the individual patient. An initial test dose may be given prior to the regular dosing schedule to detect any extreme sensitivity to adverse effects. (See ADVERSE REACTIONS.) Maximal myelosuppression usually occurs in 7 to 10 days.

Psoriasis

Recommended Starting Dose Schedule
1. Weekly single oral, IM or IV dose schedule: 10 mg to 25 mg per week until adequate response is achieved. 2. Divided oral dose schedule: 2.5 mg at 12 hour intervals for three doses.
Dosages in each schedule may be gradually adjusted to achieve optimal clinical response; 30 mg/week should not ordinarily be exceeded.

Once optimal clinical response has been achieved, each dosage schedule should be reduced to the lowest possible amount of drug and to the longest possible rest period. The use of methotrexate may permit the return to conventional topical therapy, which should be encouraged.
Milk Of Magnesia

Milk Of Magnesia

There is no fixed dosage regimen for the management of diabetes mellitus with glipizide tablets or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient’s blood glucose must also 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 may also be of value in monitoring the patient’s response to therapy.

Short-term administration of glipizide tablets may be sufficient during periods of transient loss of control in patients usually controlled well on diet.

In general, glipizide tablets should be given approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia.

Initial Dose

The recommended starting dose is 5 mg, given before breakfast. Geriatric patients or those with liver disease may be started on 2.5 mg.

Titration

Dosage adjustments should ordinarily be in increments of 2.5 mg to 5 mg, as determined by blood glucose response. At least several days should elapse between titration steps. If response to a single dose is not satisfactory, dividing that dose may prove effective. The maximum recommended once daily dose is 15 mg. Doses above 15 mg should ordinarily be divided and given before meals of adequate caloric content. The maximum recommended total daily dose is 40 mg.

Maintenance

Some patients may be effectively controlled on a once a day regimen, while others show better response with divided dosing. Total daily doses above 15 mg should ordinarily be divided. Total daily doses above 30 mg have been safely given on a b.i.d. basis to long-term patients.

In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS section).

Patients Receiving Insulin

As with other sulfonylurea-class hypoglycemics, many stable non-insulin-dependent diabetic patients receiving insulin may be safely placed on glipizide tablets. When transferring patients from insulin to glipizide tablets, the following general guidelines should be considered:
For patients whose daily insulin requirement is 20 units or less, insulin may be discontinued and glipizide tablet therapy may begin at usual dosages. Several days should elapse between glipizide titration steps. For patients whose daily insulin requirement is greater than 20 units, the insulin dose should be reduced by 50% and glipizide tablet therapy may begin at usual dosages. Subsequent reductions in insulin dosage should depend on individual patient response. Several days should elapse between glipizide titration steps.
During the insulin withdrawal period, the patient should test urine samples for sugar and ketone bodies at least 3 times daily. Patients should be instructed to contact the prescriber immediately if these tests are abnormal. In some cases, especially when patient has been receiving greater than 40 units of insulin daily, it may be advisable to consider hospitalization during the transition period.

Patients Receiving Other Oral Hypoglycemic Agents

As with other sulfonylurea-class hypoglycemics, no transition period is necessary when transferring patients to glipizide tablets. Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to glipizide tablets due to potential overlapping of drug effect.
Phenytoin

Phenytoin

When given in equal doses, phenytoin chewable tablets yield higher plasma levels than Dilantin Kapseals®*. For this reason serum concentrations should be monitored and care should be taken when switching a patient from the sodium salt to the free acid form.

Dilantin Kapseals®* is formulated with the sodium salt of phenytoin. The free acid form of phenytoin is used in Dilantin-125® Suspensions* and phenytoin chewable tablets. 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

Not for once-a-day dosing.

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 7 to 10 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 7 to 10 days.

Phenytoin chewable tablets can be either chewed thoroughly before being swallowed or swallowed whole.

Adult Dosage

Patients who have received no previous treatment may be started on two phenytoin chewable tablets 3 times daily, and the dose is then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be six to eight phenytoin chewable tablets daily; an increase to twelve phenytoin chewable tablets daily may be made, if necessary.

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 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). If the daily dosage cannot be divided equally, the larger dose should be given before retiring.
Bumetanide

Bumetanide

Dosage should be individualized with careful monitoring of patient response.

Oral Administration

The usual total daily dosage of bumetanide tablets is 0.5 mg to 2 mg and in most patients is given as a single dose.

If the diuretic response to an initial dose of bumetanide tablets is not adequate, in view of its rapid onset and short duration of action, a second or third dose may be given at 4 to 5 hour intervals up to a maximum daily dose of 10 mg. An intermittent dose schedule, whereby bumetanide tablets is given on alternate days or for 3 to 4 days with rest periods of 1 to 2 days in between, is recommended as the safest and most effective method for the continued control of edema. In patients with hepatic failure, the dosage should be kept to a minimum, and if necessary, dosage increased very carefully.

Because cross-sensitivity with furosemide has rarely been observed, bumetanide tablets can be substituted at approximately a 1:40 ratio of bumetanide tablets to furosemide in patients allergic to furosemide.

Parenteral Administration: Bumetanide injection may be administered parenterally (IV or IM) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical.

Parenteral treatment should be terminated and oral treatment instituted as soon as possible.
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 mg 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).
Clonidine Hydrochloride...

Clonidine Hydrochloride

Adults

The dose of clonidine hydrochloride tablets must be adjusted according to the patient's individual blood pressure response. The following is a general guide to its administration.

Initial Dose

0.1 mg tablet twice daily (morning and bedtime). Elderly patients may benefit from a lower initial dose.

Maintenance Dose

Further increments of 0.1 mg per day may be made at weekly intervals if necessary until the desired response is achieved. Taking the larger portion of the oral daily dose at bedtime may minimize transient adjustment effects of dry mouth and drowsiness. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day given in divided doses. Studies have indicated that 2.4 mg is the maximum effective daily dose, but doses as high as this have rarely been employed.

Renal Impairment

Patients with renal impairment may benefit from a lower initial dose. Patients should be carefully monitored. Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.
Chlorpromazine Hydrochl...

Chlorpromazine Hydrochloride

DOSAGE AND ADMINISTRATION–ADULTS

Adjust dosage to individual and the severity of his condition, recognizing that the milligram for milligram potency relationship among all dosage forms has not been precisely established clinically. It is important to increase dosage until symptoms are controlled. Dosage should be increased more gradually in debilitated or emaciated patients. In continued therapy, gradually reduce dosage to the lowest effective maintenance level, after symptoms have been controlled for a reasonable period.

The 100 mg and 200 mg tablets are for use in severe neuropsychiatric conditions.

Elderly Patients – In general, dosages in the lower range are sufficient for most elderly patients. Since they appear to be more susceptible to hypotension and neuromuscular reactions, such patients should be observed closely. Dosage should be tailored to the individual, response carefully monitored, and dosage adjusted accordingly. Dosage should be increased more gradually in elderly patients.

Psychotic Disorders – Increase dosage gradually until symptoms are controlled. Maximum improvement may not be seen for weeks or even months. Continue optimum dosage for 2 weeks; then gradually reduce dosage to the lowest effective maintenance level. Daily dosage of 200 mg is not unusual. Some patients require higher dosages (e.g., 800 mg daily is not uncommon in discharged mental patients).

Hospitalized Patients:Acute Schizophrenic or Manic States – It is recommended that initial treatment be with chlorpromazine HCI injection until patient is controlled. Usually patient becomes quiet and co-operative within 24 to 48 hours and oral doses may be substituted and increased until the patient is calm. 500 mg a day is generally sufficient. While gradual increases to 2,000 mg a day or more may be necessary, there is usually little therapeutic gain to be achieved by exceeding 1,000 mg a day for extended periods. In general, dosage levels should be lower in the elderly, the emaciated and the debilitated.

Less Acutely Disturbed – 25 mg t.i.d. Increase gradually until effective dose is reached – usually 400 mg daily.

Outpatients – 10 mg t.i.d. or q.i.d., or 25 mg b.i.d. or t.i.d.

More Severe Cases – 25 mg t.i.d. After 1 or 2 days, daily dosage may be increased by 20 to 50 mg at semi-weekly intervals until patient becomes calm and cooperative.

Prompt Control of Severe Symptoms – Initial treatment should be with intramuscular chlorpromazine. Subsequent doses should be oral, 25 to 50 mg t.i.d.

Nausea and Vomiting– 10 to 25 mg q4 to 6h, p.r.n., increased, if necessary.

Presurgical Apprehension– 25 to 50 mg, 2 to 3 hours before the operation.

Intractable Hiccups– 25 to 50 mg t.i.d. or q.i.d. If symptoms persist for 2 to 3 days, parenteral therapy is indicated.

Acute Intermittent Porphyria– 25 to 50 mg t.i.d. or q.i.d. Can usually be discontinued after several weeks, but maintenance therapy may be necessary for some patients.

DOSAGE AND ADMINISTRATION – PEDIATRIC PATIENTS (6 months to 12 years of age)

Chlorpromazine should generally not be used in pediatric patients under 6 months of age except where potentially lifesaving. It should not be used in conditions for which specific pediatric dosages have not been established.

Severe Behavioral Problems

Outpatients – Select route of administration according to severity of patient's condition and increase dosage gradually as required. Oral: ¼ mg/lb body weight q4 to 6h, p.r.n. (e.g., for 40 lb child – 10 mg q4 to 6h).

Hospitalized Patients – As with outpatients, start with low doses and increase dosage gradually. In severe behavior disorders higher dosages (50 to 100 mg daily and in older children, 200 mg daily or more) may be necessary. There is little evidence that behavior improvement in severely disturbed mentally retarded patients is further enhanced by doses beyond 500 mg per day.

Nausea and Vomiting– Dosage and frequency of administration should be adjusted according to the severity of the symptoms and response of the patient. The duration of activity following intramuscular administration may last up to 12 hours. Subsequent doses may be given by the same route if necessary. Oral: ¼ mg/lb body weight (e.g., 40 lb child – 10 mg q4 to 6h).

Presurgical Apprehension–¼ mg/lb body weight orally 2 to 3 hours before operation.
Allopurinol

Allopurinol

The dosage of allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The average is 200 to 300 mg/day for patients with mild gout and 400 to 600 mg/day for those with moderately severe tophaceous gout. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Dosage requirements in excess of 300 mg should be administered in divided doses. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily. To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage.

Normal serum urate levels are usually achieved in 1 to 3 weeks. The upper limit of normal is about 7 mg/dL for men and postmenopausal women and 6 mg/dL for premenopausal women. Too much reliance should not be placed on a single uric acid determination since, for technical reasons, estimation of uric acid may be difficult. By selecting the appropriate dosage and, in certain patients, using uricosuric agents concurrently, it is possible to reduce serum uric acid to normal or, if desired, to as low as 2 to 3 mg/dL and keep it there indefinitely.

While adjusting the dosage of allopurinol in patients who are being treated with colchicine and/or anti-inflammatory agents, it is wise to continue the latter therapy until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months.

In transferring a patient from a uricosuric agent to allopurinol, the dose of the uricosuric agent should be gradually reduced over a period of several weeks and the dose of allopurinol gradually increased to the required dose needed to maintain a normal serum uric acid level.

It should also be noted that allopurinol is generally better tolerated if taken following meals. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.

Since allopurinol and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of allopurinol should consequently be reduced. With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of allopurinol is suitable. When the creatine clearance is less than 10 mL/min, the daily dosage should not exceed 100 mg. With extreme renal impairment (creatinine clearance less than 3 mL/min) the interval between doses may also need to be lengthened.

The correct size and frequency of dosage for maintaining the serum uric acid just within the normal range is best determined by using the serum uric acid level as an index.

For the prevention of uric acid nephropathy during the vigorous therapy of neoplastic disease, treatment with 600 to 800 mg daily for 2 or 3 days is advisable together with a high fluid intake. Otherwise similar considerations to the above recommendations for treating patients with gout govern the regulation of dosage for maintenance purposes in secondary hyperuricemia.

The dose of allopurinol recommended for management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 to 300 mg/day in divided doses or as the single equivalent. This dose may be adjusted up or down depending upon the resultant control of the hyperuricosuria based upon subsequent 24 hour urinary urate determinations. Clinical experience suggests that patients with recurrent calcium oxalate stones may also benefit from dietary changes such as the reduction of animal protein, sodium, refined sugars, oxalate-rich foods, and excessive calcium intake, as well as an increase in oral fluids and dietary fiber.

Children, 6 to 10 years of age, with secondary hyperuricemia associated with malignancies may be given 300 mg allopurinol daily while those under 6 years are generally given 150 mg daily. The response is evaluated after approximately 48 hours of therapy and a dosage adjustment is made if necessary.
Chlorthalidone

Chlorthalidone

Therapy should be initiated with the lowest possible dose. This dose should be titrated according to individual patient response to gain maximal therapeutic benefit while maintaining lowest dosage possible. A single dose given in the morning with food is recommended; divided daily doses are unnecessary.

Hypertension

Initiation: Therapy, in most patients, should be initiated with a single daily dose of 25 mg. If the response is insufficient after a suitable trial, the dosage may be increased to a single daily dose of 50 mg. If additional control is required, the dosage of chlorthalidone may be increased to 100 mg once daily or a second antihypertensive drug (step 2 therapy) may be added. Dosage above 100 mg daily usually does not increase effectiveness. Increases in serum uric acid and decreases in serum potassium are dose-related over the 25 to 100 mg/day range.

Maintenance: Maintenance doses may be lower than initial doses and should be adjusted according to individual patient response. Effectiveness is well sustained during continued use.

Edema

Initiation: Adults, initially 50 to 100 mg daily, or 100 mg on alternate days. Some patients may require 150 to 200 mg at these intervals or up to 200 mg daily. Dosages above this level, however, do not usually produce a greater response.

Maintenance: Maintenance doses may often be lower than initial doses and should be adjusted according to individual patient response. Effectiveness is well sustained during continued use.
Diphenoxylate Hydrochlo...

Diphenoxylate Hydrochloride And Atropine Sulfate

DO NOT EXCEED RECOMMENDED DOSAGE.

Adults

The recommended initial dosage is two tablets four times daily (20 mg per day). Most patients will require this dosage until initial control has been achieved, after which the dosage may be reduced to meet individual requirements. Control may often be maintained with as little as 5 mg (two tablets) daily.

Clinical improvement of acute diarrhea is usually observed within 48 hours. If clinical improvement of chronic diarrhea after treatment with a maximum daily dose of 20 mg of diphenoxylate hydrochloride is not observed within 10 days, symptoms are unlikely to be controlled by further administration.

Children

Diphenoxylate hydrochloride and atropine sulfate is not recommended in children under 2 years of age and should be used with special caution in young children (see WARNINGS and PRECAUTIONS). The nutritional status and degree of dehydration must be considered. In children under 13 years of age, use oral solution. Do not use tablets for this age group.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
Amiodarone Hydrochlorid...

Amiodarone Hydrochloride

2.1 General Dosing Information

The patient should be placed on a standard cholesterol-lowering diet before receiving pravastatin sodium tablets and should continue on this diet during treatment with pravastatin sodium tablets [see NCEP Treatment Guidelines for details on dietary therapy].

2.2 Adult Patients

The recommended starting dose is 40 mg once daily. If a daily dose of 40 mg does not achieve desired cholesterol levels, 80 mg once daily is recommended. In patients with significant renal impairment, a starting dose of 10 mg daily is recommended. Pravastatin sodium tablets can be administered orally as a single dose at any time of the day, with or without food. Since the maximal effect of a given dose is seen within 4 weeks, periodic lipid determinations should be performed at this time and dosage adjusted according to the patient’s response to therapy and established treatment guidelines.

2.3 Pediatric Patients

Children (Ages 8 to 13 Years, Inclusive)

The recommended dose is 20 mg once daily in children 8 to 13 years of age. Doses greater than 20 mg have not been studied in this patient population.

Adolescents (Ages 14 to 18 Years)

The recommended starting dose is 40 mg once daily in adolescents 14 to 18 years of age. Doses greater than 40 mg have not been studied in this patient population.

Children and adolescents treated with pravastatin should be reevaluated in adulthood and appropriate changes made to their cholesterol-lowering regimen to achieve adult goals for LDL-C [see Indications and Usage (1.2)].

2.4 Concomitant Lipid-Altering Therapy

Pravastatin sodium tablets may be used with bile acid resins. When administering a bile-acid-binding resin (e.g., cholestyramine, colestipol) and pravastatin, pravastatin sodium tablets should be given either 1 hour or more before or at least 4 hours following the resin [see Clinical Pharmacology (12.3)].

2.5 Dosage in Patients Taking Cyclosporine

In patients taking immunosuppressive drugs such as cyclosporine concomitantly with pravastatin, therapy should begin with 10 mg of pravastatin sodium once-a-day at bedtime and titration to higher doses should be done with caution. Most patients treated with this combination received a maximum pravastatin sodium dose of 20 mg/day. In patients taking cyclosporine, therapy should be limited to 20 mg of pravastatin sodium once daily [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].

2.6 Dosage in Patients Taking Clarithromycin

In patients taking clarithromycin, therapy should be limited to 40 mg of pravastatin sodium once daily [see Drug Interactions (7.2)].
Magnesium Sulfate

Magnesium Sulfate

Carefully consider the potential benefits and risks of sulindac tablets and other treatment options before deciding to use sulindac 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 sulindac tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

Sulindac tablets should be administered orally twice a day with food. The maximum dosage is 400 mg per day. Dosages above 400 mg per day are not recommended.

In osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, the recommended starting dosage is 150 mg twice a day. The dosage may be lowered or raised depending on the response.

A prompt response (within one week) can be expected in about one-half of patients with osteoarthritis, ankylosing spondylitis, and rheumatoid arthritis. Others may require longer to respond.

In acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis) and acute gouty arthritis, the recommended dosage is 200 mg twice a day. After a satisfactory response has been achieved, the dosage may be reduced according to the response. In acute painful shoulder, therapy for 7 to 14 days is usually adequate. In acute gouty arthritis, therapy for 7 days is usually adequate.
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.
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 for the tablet dosage form 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

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.
Omeprazole

Omeprazole

Omeprazole delayed-release capsules should be taken before eating. In the clinical trials, antacids were used concomitantly with omeprazole delayed-release capsules.

Patients should be informed that the omeprazole delayed-release capsules 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 4 weeks. Some patients may require an additional 4 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 3 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 [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 delayed-release capsules 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.
Non-drowsy Sinus Conges...

Non-drowsy Sinus Congestion And Pain

(See table below.)

Monitoring of blood levels has increased the efficacy and safety of anticonvulsants (see PRECAUTIONS, Laboratory Tests). Dosage should be adjusted to the needs of the individual patient. A low initial daily dosage with a gradual increase is advised. As soon as adequate control is achieved, the dosage may be reduced very gradually to the minimum effective level. Medication should be taken with meals.

Conversion of patients from oral carbamazepine tablets to carbamazepine suspension: Patients should be converted by administering the same number of mg per day in smaller, more frequent doses (i.e., b.i.d. tablets to t.i.d. suspension).

Epilepsy

(See INDICATIONS AND USAGE.)

Adults and Children Over 12 Years of Age

Initial: 200 mg b.i.d. Increase at weekly intervals by adding up to 200 mg/day using a t.i.d. or q.i.d. regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily in children 12 to 15 years of age, and 1200 mg daily in patients above 15 years of age. Doses up to 1600 mg daily have been used in adults in rare instances. Maintenance: Adjust dosage to the minimum effective level, usually 800 to 1200 mg daily.

Children 6 to 12 Years of Age

Initial: 100 mg b.i.d. Increase at weekly intervals by adding up to 100 mg/day using a t.i.d. or q.i.d. regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily. Maintenance: Adjust dosage to the minimum effective level, usually 400 to 800 mg daily.

Children Under 6 Years of Age

Initial: 10 to 20 mg/kg/day b.i.d. or t.i.d. Increase weekly to achieve optimal clinical response administered t.i.d. or q.i.d. Maintenance: Ordinarily, optimal clinical response is achieved at daily doses below 35 mg/kg. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the therapeutic range. No recommendation regarding the safety of carbamazepine for use at doses above 35 mg/kg/24 hours can be made.

Combination Therapy

Carbamazepine tablets and Carbamazepine tablets (chewable) may be used alone or with other anticonvulsants. When added to existing anticonvulsant therapy, the drug should be added gradually while the other anticonvulsants are maintained or gradually decreased, except phenytoin, which may have to be increased (see PRECAUTIONS, Drug Interactions, and Usage in Pregnancy, Teratogenic Effects, Pregnancy Category D).

Trigeminal Neuralgia

(See INDICATIONS AND USAGE.)

Initial: On the first day, 100 mg b.i.d. for a total daily dose of 200 mg. This daily dose may be increased by up to 200 mg/day using increments of 100 mg every 12 hours only as needed to achieve freedom from pain. Do not exceed 1200 mg daily. Maintenance: Control of pain can be maintained in most patients with 400 to 800 mg daily. However, some patients may be maintained on as little as 200 mg daily, while others may require as much as 1200 mg daily. At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or even to discontinue the drug.
Dosage Information * Tablet = Chewable or conventional tablets
Initial Dose

Subsequent Dose

Maximum Daily Dose

Indication

Tablet*

Epilepsy

Under 6 yr

10 to 20 mg/kg/day b.i.d. or t.i.d.

Increase weekly to achieve optimal clinical response, t.i.d. or q.i.d.

35 mg/kg/24 hr (see DOSAGE AND ADMINISTRATIONsection above)

6 to 12 yr

100 mg b.i.d. (200 mg/day)

Add up to 100 mg/day at weekly intervals, t.i.d. or q.i.d.

1000 mg/24 hr

Over 12 yr

200 mg b.i.d. (400 mg/day)

Add up to 200 mg/day at weekly intervals, t.i.d. or q.i.d.

1000 mg/24 hr (12 to 15 yr) 1200 mg/24 hr (> 15 yr) 1600 mg/24 hr (adults, in rare instances)

Trigeminal Neuralgia

100 mg b.i.d. (200 mg/day)

Add up to 200 mg/day in increments of 100 mg every 12 hr

1200 mg/24 hr
Buspirone Hydrochloride...

Buspirone Hydrochloride

The recommended initial dose is 15 mg daily (7.5 mg b.i.d.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day, as needed. The maximum daily dosage should not exceed 60 mg per day. In clinical trials allowing dose titration, divided doses of 20 mg to 30 mg per day were commonly employed.

The bioavailability of buspirone is increased when given with food as compared to the fasted state (see CLINICAL PHARMACOLOGY). Consequently, patients should take buspirone in a consistent manner with regard to the timing of dosing; either always with or always without food.

When buspirone is to be given with a potent inhibitor of CYP3A4 the dosage recommendations described in the PRECAUTIONS: Drug Interactions section should be followed.
Paricalcitol

Paricalcitol

The dose of prazosin hydrochloride capsules should be adjusted according to the patient’s individual blood pressure response. The following is a guide to its administration:

Initial Dose

1 mg two or three times a day (see WARNINGS).

Maintenance Dose

Dosage may be slowly increased to a total daily dose of 20 mg given in divided doses. The therapeutic dosages most commonly employed have ranged from 6 mg to 15 mg daily given in divided doses. Doses higher than 20 mg usually do not increase efficacy, however a few patients may benefit from further increases up to a daily dose of 40 mg given in divided doses. After initial titration some patients can be maintained adequately on a twice daily dosage regimen.

Use With Other Drugs

When adding a diuretic or other antihypertensive agent, the dose of prazosin hydrochloride capsules should be reduced to 1 mg or 2 mg three times a day and retitration then carried out.

Concomitant administration of prazosin hydrochloride capsules with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking prazosin hydrochloride capsules.
Relax-tone

Relax-tone

Dosage of thiothixene capsules should be individually adjusted depending on the chronicity and severity of the symptoms of schizophrenia. In general, small doses should be used initially and gradually increased to the optimal effective level, based on patient response.

Some patients have been successfully maintained on once a day thiothixene capsule therapy.

The use of thiothixene capsules in children under 12 years of age is not recommended because safe conditions for its use have not been established.

In milder conditions, an initial dose of 2 mg three times daily is recommended. If indicated, a subsequent increase to 15 mg/day total daily dose is often effective.

In more severe conditions, an initial dose of 5 mg twice daily is recommended.

The usual optimal dose is 20 mg to 30 mg daily. If indicated, an increase to 60 mg/day total daily dose is often effective. Exceeding a total daily dose of 60 mg rarely increases the beneficial response.
Cough Control

Cough Control

Rifampin can be administered by the oral route (see INDICATIONS AND USAGE). See CLINICAL PHARMACOLOGY for dosing information in patients with renal failure.

Tuberculosis

Adults: 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, orally.

Pediatric Patients: 10 to 20 mg/kg, not to exceed 600 mg/day, orally.

It is recommended that oral rifampin capsule be administered once daily, either 1 hour before or 2 hours after a meal with a full glass of water.

Rifampin is indicated in the treatment of all forms of tuberculosis. A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide (e.g., RIFATER® (Sanofi-aventis U.S. LLC)) is recommended in the initial phase of short-course therapy which is usually continued for 2 months. The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Centers for Disease Control and Prevention recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered.

Following the initial phase, treatment should be continued with rifampin and isoniazid (e.g., RIFAMATE® (Sanofi-aventis U.S. LLC)) for at least 4 months. Treatment should be continued for longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is HIV positive.

Meningococcal Carriers

Adults: For adults, it is recommended that 600 mg rifampin be administered twice daily for two days.

Pediatric Patients: Pediatric patients 1 month of age or older: 10 mg/kg (not to exceed 600 mg per dose) every 12 hours for two days.

Pediatric patients under 1 month of age: 5 mg/kg every 12 hours for two days.

Preparation of Extemporaneous Oral Suspension

For pediatric and adult patients in whom capsule swallowing is difficult or where lower doses are needed, a liquid suspension may be prepared as follows:

Rifampin 1% w/v suspension (10 mg/mL) can be compounded using one of four syrups-Simple Syrup (Syrup NF), Simple Syrup (Humco Laboratories), Syrpalta® Syrup (Emerson Laboratories) or Raspberry Syrup (Humco Laboratories).
• Empty the contents of four Rifampin 300 mg capsules or eight Rifampin 150 mg capsules onto a piece of weighing paper. • If necessary, gently crush the capsule contents with a spatula to produce a fine powder. • Transfer the rifampin powder blend to a 4-ounce amber glass or plastic (high density polyethylene [HDPE], polypropylene, or polycarbonate) prescription bottle. • Rinse the paper and spatula with 20 mL of one of the above mentioned syrups, and add the rinse to the bottle. Shake vigorously. • Add 100 mL of syrup to the bottle and shake vigorously.
This compounding procedure results in a 1% w/v suspension containing 10 mg rifampin/mL. Stability studies indicate that the suspension is stable when stored at room temperature (25 ± 3° C) or in a refrigerator (2 to 8° C) for four weeks. This extemporaneously prepared suspension must be shaken well prior to administration.
Aptiom

Aptiom

Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who require doses greater than 4 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects.

Anxiety Disorders and Transient Symptoms of Anxiety

Treatment for patients with anxiety should be initiated with a dose of 0.25 mg to 0.5 mg given three times daily. The dose may be increased to achieve a maximum therapeutic effect, at intervals of 3 to 4 days, to a maximum daily dose of 4 mg, given in divided doses. The lowest possible effective dose should be employed and the need for continued treatment reassessed frequently. The risk of dependence may increase with dose and duration of treatment.

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 3 days. Some patients may require an even slower dosage reduction.

Panic Disorder

The successful treatment of many panic disorder patients has required the use of alprazolam at doses greater than 4 mg daily. In controlled trials conducted to establish the efficacy of alprazolam in panic disorder, doses in the range of 1 mg to 10 mg daily were used. The mean dosage employed was approximately 5 mg to 6 mg daily. Among the approximately 1,700 patients participating in the panic disorder development program, about 300 received alprazolam in dosages of greater than 7 mg/day, including approximately 100 patients who received maximum dosages of greater than 9 mg/day. Occasional patients required as much as 10 mg a day to achieve a successful response.

Dose Titration

Treatment may be initiated with a dose of 0.5 mg three times 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 per day. Slower titration to the dose levels greater than 4 mg/day may be advisable to allow full expression of the pharmacodynamic effect of alprazolam. To lessen the possibility of interdose symptoms, the times of administration should be distributed as evenly as possible throughout the waking hours, that is, on a three or four times per day schedule.

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

For patients receiving doses greater than 4 mg/day, periodic reassessment and consideration of dosage reduction is advised. In a controlled post-marketing dose-response study, patients treated with doses of alprazolam greater than 4 mg/day for 3 months were able to taper to 50% of their total maintenance dose without apparent loss of clinical benefit. Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided. (See WARNINGS, PRECAUTIONS, DRUG ABUSE AND DEPENDENCE.)

The necessary duration of treatment for panic disorder patients responding to alprazolam is unknown. 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, 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 3 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 post-marketing 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 3 days, with the understanding that some patients may benefit from an even more gradual discontinuation. Some patients may prove resistant to all discontinuation regimens.

Dosing in Special Populations

In elderly patients, in patients with advanced liver disease or in patients with debilitating disease, the usual starting dose is 0.25 mg, given two or three times daily. This may be gradually increased if needed and tolerated. The elderly may be especially sensitive to the effects of benzodiazepines. If side effects occur at the recommended starting dose, the dose may be lowered.
Mucus Relief Dm

Mucus Relief Dm

Duodenal Ulcer

Acute Therapy

The recommended adult oral dosage for active duodenal ulcer is 40 mg once a day at bedtime. Most patients heal within 4 weeks; there is rarely reason to use famotidine tablets at full dosage for longer than 6 to 8 weeks. A regimen of 20 mg b.i.d. is also effective.

Maintenance Therapy

The recommended adult oral dose is 20 mg once a day at bedtime.

Benign Gastric Ulcer

Acute Therapy

The recommended adult oral dosage for active benign gastric ulcer is 40 mg once a day at bedtime.

Gastroesophageal Reflux Disease (GERD)

The recommended oral dosage for treatment of adult patients with symptoms of GERD is 20 mg b.i.d. for up to 6 weeks. The recommended oral dosage for the treatment of adult patients with esophagitis including erosions and ulcerations and accompanying symptoms due to GERD is 20 mg or 40 mg b.i.d. for up to 12 weeks (see CLINICAL PHARMACOLOGY IN ADULTS: Clinical Studies).

Dosage for Pediatric Patients < 1 Year of Age

Gastroesophageal Reflux Disease (GERD)

(See PRECAUTIONS: Pediatric Patients < 1 Year of Age.)

The studies described in PRECAUTIONS: Pediatric Patients < 1 Year of Age suggest the following starting doses in pediatric patients < 1 year of age: Gastroesophageal Reflux Disease (GERD) - 0.5 mg/kg/dose of famotidine oral suspension for the treatment of GERD for up to 8 weeks once daily in patients < 3 months of age and 0.5 mg/kg/dose twice daily in patients 3 months to < 1 year of age. Patients should also be receiving conservative measures (e.g., thickened feedings). The use of intravenous famotidine in pediatric patients < 1 year of age with GERD has not been adequately studied.

Dosage for Pediatric Patients 1 to 16 Years of Age

(See PRECAUTIONS: Pediatric Patients 1 to 16 Years of Age.)

The studies described in PRECAUTIONS: Pediatric Patients 1 to 16 Years of Age suggest the following starting doses in pediatric patients 1 to 16 years of age:
Peptic ulcer - 0.5 mg/kg/day p.o. at bedtime or divided b.i.d. up to 40 mg/day. Gastroesophageal Reflux Disease with or without esophagitis including erosions and ulcerations - 1 mg/kg/day p.o. divided b.i.d. up to 40 mg b.i.d.
While published uncontrolled studies suggest effectiveness of famotidine in the treatment of gastroesophageal reflux disease and peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Published uncontrolled clinical studies in pediatric patients 1 to 16 years of age have employed doses up to 1 mg/kg/day for peptic ulcer and 2 mg/kg/day for GERD with or without esophagitis including erosions and ulcerations.

Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas)

The dosage of famotidine tablets in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose for pathological hypersecretory conditions is 20 mg q6h. In some patients, a higher starting dose may be required. Doses should be adjusted to individual patient needs and should continue as long as clinically indicated. Doses up to 160 mg q6h have been administered to some adult patients with severe Zollinger-Ellison Syndrome.

Concomitant Use of Antacids

Antacids may be given concomitantly if needed.

Dosage Adjustment for Patients with Moderate or Severe Renal Insufficiency

In adult patients with moderate (creatinine clearance < 50 mL/min) or severe (creatinine clearance < 10 mL/min) renal insufficiency, the elimination half-life of famotidine is increased. For patients with severe renal insufficiency, it may exceed 20 hours, reaching approximately 24 hours in anuric patients. Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of famotidine tablets may be reduced to half the dose or the dosing interval may be prolonged to 36 to 48 hours as indicated by the patient's clinical response.

Based on the comparison of pharmacokinetic parameters for famotidine tablets in adults and pediatric patients, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered.

HOW SUPPLIED:

Famotidine Tablets, USP are available containing either 20 mg of famotidine, USP.

The 20 mg tablets are yellow film-coated, round, unscored tablets debossed with M over F1 on one side of the tablet and blank on the other side. They are available as follows:

NDC 51079-966-20 – Unit dose blister packages of 100 (10 cards of 10 tablets each).NDC 51079-966-19 – Robot Ready blister packages of 25 (25 cards of 1 tablet each).

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]Protect from light.

Manufactured by:Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.

Distributed by:Mylan Institutional Inc. Rockford, IL 61103 U.S.A.

S-121784/15
Fenofibric Acid

Fenofibric Acid

2.1 General Considerations

Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibric acid delayed-release capsules as monotherapy or coadministered with a statin, and should continue this diet during treatment. Fenofibric acid delayed-release capsules can be taken without regard to meals. Patients should be advised to swallow fenofibric acid delayed-release capsules whole. Do not open, crush, dissolve or chew capsules. Serum lipids should be monitored periodically.

2.2 Coadministration Therapy with Statins for the Treatment of Mixed Dyslipidemia

Fenofibric acid delayed-release capsules 135 mg may be coadministered with an HMG-CoA reductase inhibitor (statin) in patients with mixed dyslipidemia. For convenience, the daily dose of fenofibric acid delayed-release capsules may be taken at the same time as a statin, according to the dosing recommendations for each medication. Coadministration with the maximum dose of a statin has not been evaluated in clinical studies and should be avoided unless the benefits are expected to outweigh the risks.

2.3 Severe Hypertriglyceridemia

The initial dose of fenofibric acid delayed-release capsules is 45 mg to 135 mg once daily. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 135 mg once daily.

2.4 Primary Hypercholesterolemia or Mixed Dyslipidemia

The dose of fenofibric acid delayed-release capsules is 135 mg once daily.

2.5 Impaired Renal Function

Treatment with fenofibric acid delayed-release capsules should be initiated at a dose of 45 mg once daily in patients with mild to moderate renal impairment and should only be increased after evaluation of the effects on renal function and lipid levels at this dose. The use of fenofibric acid delayed-release capsules should be avoided in patients with severely impaired renal function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.6 Geriatric Patients

Dose selection for the elderly should be made on the basis of renal function [see Use in Specific Populations (8.5)].
Cetirizine Hydrochlorid...

Cetirizine Hydrochloride

adults and children6 years and over

one 10 mg tablet once daily; do not take more than one 10 mg tablet in 24 hours. A 5 mg product may be appropriate for less severe symptoms.

adults 65 yearsand over

ask a doctor

children under6 years of age

ask a doctor

consumers with liveror kidney disease

ask a doctor
Fexofenadine Hydrochlor...

Fexofenadine Hydrochloride

adults and children 12 years of age and over

take one 60 mg tablet with water every 12 hours; do not take more than 2 tablets in 24 hours

children under 12 years of age

do not use

adults 65 years of age and older

ask a doctor

consumers with kidney disease

ask a doctor

Directions - 180 mg (24 Hour Relief)

adults and children 12 years of age and over

take one 180 mg tablet with water once a day; do not take more than 1 tablet in 24 hours

children under 12 years of age

do not use

adults 65 years of age and older

ask a doctor

consumers with kidney disease

ask a doctor
Entacapone

Entacapone

The recommended dose of Entacapone Tablets 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 trials, 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 dyskinesias 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 trials, 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 the neuroleptic malignant syndrome (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 have not been systematically evaluated, it seems prudent to withdraw patients slowly if the decision to discontinue treatment is made.
Diazepam

Diazepam

Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In such cases dosage should be increased cautiously to avoid adverse effects.
ADULTS: USUAL DAILY DOSE: Management of Anxiety Disorders and Reliefof Symptoms of Anxiety Depending upon severity of symptoms - 2mgto 10 mg, 2 or 4 times daily Symptomatic Relief in Acute AlcoholWithdrawal 10 mg, 3 or 4 times during the first 24 hours,reducing to 5 mg, 3 or 4 times daily as needed Adjunctively for Relief of Skeletal MuscleSpasm 2 mg to 10 mg, 3 or 4 times daily Adjunctively in Convulsive Disorders 2 mg to 10 mg, 2 to 4 times daily Geriatric Patients, or in the presence ofdebilitating disease 2 mg to 2.5 mg, 1 or 2 times daily initially;increase gradually as needed and tolerated PEDIATRIC PATIENTS: Because of varied responses to CNS-actingdrugs, initiate therapy with lowest dose and increase as required. Not for use in pediatric patients under 6 months 1 mg to 2.5 mg, 3 or 4 times daily initially;increase gradually as needed and tolerated
Hydrocodone Bitartrate ...

Hydrocodone Bitartrate And Acetaminophen

(For children’s dosage and administration, see below.) Dosage should be increased more gradually in debilitated or emaciated patients.

Elderly Patients

In general, dosages in the lower range are sufficient for most elderly patients. Since they appear to be more susceptible to hypotension and neuromuscular reactions, such patients should be observed closely. Dosage should be tailored to the individual, response carefully monitored and dosage adjusted accordingly. Dosage should be increased more gradually in elderly patients.

1. To Control Severe Nausea and Vomiting

Adjust dosage to the response of the individual. Begin with the lowest recommended dosage.

Oral Dosage - Tablets

Usually one 5 mg or 10 mg tablet 3 or 4 times daily. Daily dosages above 40 mg should be used only in resistant cases.

2. In Adult Psychiatric Disorders

Adjust dosage to the response of the individual and according to the severity of the condition. Begin with the lowest recommended dose. Although response ordinarily is seen within a day or 2, longer treatment is usually required before maximal improvement is seen.

Oral Dosage

Non-Psychotic Anxiety

Usual dosage is 5 mg 3 or 4 times daily. Do not administer in doses of more than 20 mg per day or for longer than 12 weeks.

Psychotic Disorders including Schizophrenia

In relatively mild conditions, as seen in private psychiatric practice or in outpatient clinics, dosage is 5 mg or 10 mg 3 or 4 times daily.

In moderate to severe conditions, for hospitalized or adequately supervised patients, usual starting dosage is 10 mg 3 or 4 times daily. Increase dosage gradually until symptoms are controlled or side effects become bothersome. When dosage is increased by small increments every 2 or 3 days, side effects either do not occur or are easily controlled. Some patients respond satisfactorily on 50 mg to 75 mg daily.

In more severe disturbances, optimum dosage is usually 100 mg to 150 mg daily.
Cold And Flu

Cold And Flu

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 vs. 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 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.

An additional dose of montelukast 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 15 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.

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 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.
Oxybutynin Chloride

Oxybutynin Chloride

Oxybutynin chloride extended-release tablets must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed.

Oxybutynin chloride extended-release tablets may be administered with or without food.

2.1 Adults

The recommended starting dose of oxybutynin chloride extended-release tablets is 5 mg or 10 mg once daily at approximately the same time each day. Dosage may be adjusted in 5 mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 30 mg/day). In general, dosage adjustment may proceed at approximately weekly intervals.

2.2 Pediatric Patients Aged 6 Years of Age and Older

The recommended starting dose of oxybutynin chloride extended-release tablets is 5 mg once daily at approximately the same time each day. Dosage may be adjusted in 5 mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 20 mg/day).
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 mg 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 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, 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 monotherapy does not result in adequate glycemic control, a thiazolidinedione may be added. If thiazolidinedione monotherapy does not provide adequate control, repaglinide may be added. The starting dose and dose adjustments for repaglinide combination therapy is the same as for repaglinide 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.
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 6 months.

Retreatment of Paget’s Disease

Retreatment with alendronate sodium tablets may be considered, following a 6-month post-treatment evaluation period in patients who have relapsed, based on increases in serum alkaline phosphatase, which should be measured periodically. Retreatment 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 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, a alendronate sodium tablet should be swallowed with a full glass of water (6 to 8 oz). 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 are 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.
Abacavir Sulfate

Abacavir Sulfate

• 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

The recommended oral dose of abacavir oral solution in HIV-1-infected pediatric patients aged 3 months and older is 8 mg/kg twice daily (up to a maximum of 300 mg twice daily) in combination with other antiretroviral agents.

Abacavir is also available as a 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 Tablets in Pediatric Patients
Weight (kg)

Dosage Regimen Using Scored Tablet

Total Daily Dose

AM Dose

PM Dose

14 to 21

½ tablet (150 mg)

½ tablet (150 mg)

300 mg

> 21 to < 30

½ tablet (150 mg)

1 tablet (300 mg)

450 mg

≥ 30

1 tablet (300 mg)

1 tablet (300 mg)

600 mg

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 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.
Mycophenolic Acid

Mycophenolic Acid

2.1 Dosage in Adult Kidney Transplant Patients

The recommended dose of mycophenolic acid delayed-release tablets is 720 mg administered twice daily (1440 mg total daily dose).

2.2 Dosage in Pediatric Kidney Transplant Patients

The recommended dose of mycophenolic acid delayed-release tablets in conversion (at least 6 months post-transplant) pediatric patients age 5 years and older is 400 mg/m2 body surface area (BSA) administered twice daily (up to a maximum dose of 720 mg administered twice daily).

2.3 Administration

Mycophenolic acid delayed-release tablets should be taken on an empty stomach, one hour before or 2 hours after food intake [see Clinical Pharmacology (12.3)].

Mycophenolic acid delayed-release tablets should not be crushed, chewed, or cut prior to ingesting. The tablets should be swallowed whole in order to maintain the integrity of the enteric coating.

Pediatric patients with a BSA of 1.19 to 1.58 m2 may be dosed either with three mycophenolic acid delayed-release 180 mg tablets, or one 180 mg tablet plus one 360 mg tablet twice daily (1080 mg daily dose). Patients with a BSA of > 1.58 m2 may be dosed either with four mycophenolic acid delayed-release 180 mg tablets, or two mycophenolic acid delayed-release 360 mg tablets twice daily (1440 mg daily dose). Pediatric doses for patients with BSA < 1.19 m2 cannot be accurately administered using currently available formulations of mycophenolic acid delayed-release tablets.
Atorvastatin Calcium

Atorvastatin Calcium

2.1 Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

The recommended starting dose of atorvastatin calcium tablets is 10 mg or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin calcium tablets is 10 mg to 80 mg once daily. Atorvastatin calcium tablets can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin calcium tablets should be individualized according to patient characteristics such as goal of therapy and response (see current NCEP Guidelines). After initiation and/or upon titration of atorvastatin calcium tablets, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

2.2 Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 Years of Age)

The recommended starting dose of atorvastatin calcium tablets is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy [see current NCEP Pediatric Panel Guidelines, Clinical Pharmacology (12), and Indications and Usage (1.2)]. Adjustments should be made at intervals of 4 weeks or more.

2.3 Homozygous Familial Hypercholesterolemia

The dosage of atorvastatin calcium tablets in patients with homozygous FH is 10 mg to 80 mg daily. Atorvastatin calcium 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.

2.4 Concomitant Lipid-lowering Therapy

Atorvastatin calcium tablets may be used with bile acid resins. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].

2.5 Dosage in Patients with Renal Impairment

Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin calcium tablets; thus, dosage adjustment in patients with renal dysfunction is not necessary [see Warnings and Precautions, Skeletal Muscle (5.1), Clinical Pharmacology, Pharmacokinetics (12.3)].

2.6 Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors

In patients taking cyclosporine or the HIV protease inhibitors (tipranavir plus ritonavir) or the hepatitis C protease inhibitor (telaprevir), therapy with atorvastatin calcium tablets should be avoided. In patients with HIV taking lopinavir plus ritonavir, caution should be used when prescribing atorvastatin calcium tablets and the lowest dose necessary employed. In patients taking clarithromycin, itraconazole, or in patients with HIV taking a combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, therapy with atorvastatin calcium tablets should be limited to 20 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, therapy with atorvastatin calcium tablets should be limited to 40 mg, and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin calcium tablets is employed [see Warnings and Precautions, Skeletal Muscle (5.1), Drug Interactions (7)].
Tolterodine Tartrate

Tolterodine Tartrate

2.1 Dosing Information

The recommended dose of tolterodine tartrate extended-release capsules is 4 mg once daily with water and swallowed whole. The dose may be lowered to 2 mg daily based on individual response and tolerability; however, limited efficacy data are available for tolterodine tartrate extended-release capsules 2 mg [see Clinical Studies (14)].

2.2 Dosage Adjustment in Specific Populations

For patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10 to 30 mL/min), the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr < 10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [see Warnings and Precautions (5.6), Use in Specific Populations (8.6, 8.7)].

2.3 Dosage Adjustment in Presence of Concomitant Drugs

For patients who are taking drugs that are potent inhibitors of CYP3A4 [e.g., ketoconazole, clarithromycin, ritonavir], the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily [see Drug Interactions (7.2)].
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 tablets 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 mg 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 tablets 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 tablets 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 I.V. beta-blocker or clinical estimate that there is a contraindication, the I.V. 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 7 days (if the I.V. dosing is excluded).

Although the demonstration of efficacy of atenolol is based entirely on data from the first 7 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 1 to 3 years if there are no contraindications.

Atenolol tablets are 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/1.73m2) Atenolol Elimination Half-Life (hrs) Maximum Dosage
15 to 35

16 to 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 tablets therapy is planned, it should be achieved gradually and patients should be carefully observed and advised to limit physical activity to a minimum.
Benazepril Hydrochlorid...

Benazepril Hydrochloride

Hypertension

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. Dosage adjustment should be based on measurement of peak (2 to 6 hours after dosing) and trough responses. If a once daily regimen does not give adequate trough response, an increase in dosage or divided administration should be considered. If blood pressure is not controlled with benazepril hydrochloride tablets alone, a diuretic can be added.

Total daily doses above 80 mg have not been evaluated.

Concomitant administration of benazepril hydrochloride 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 benazepril hydrochloride tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with benazepril hydrochloride tablets (see WARNINGS). Then, if blood pressure is not controlled with benazepril hydrochloride tablets alone, diuretic therapy should be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg benazepril hydrochloride tablets should be used to avoid excessive hypotension.

Pediatrics

In children, doses of benazepril hydrochloride tablets between 0.1 and 0.6 mg/kg once daily have been studied, and doses greater than 0.1 mg/kg were shown to reduce blood pressure (see CLINICAL PHARMACOLOGY: Pharmacodynamics). Based on this, the recommended starting dose of benazepril hydrochloride tablets is 0.2 mg/kg once per day as monotherapy. Doses above 0.6 mg/kg (or in excess of 40 mg daily) have not been studied in pediatric patients.

For pediatric patients who cannot swallow tablets, or for whom the calculated dosage (mg/kg) does not correspond to the available tablet strengths for benazepril hydrochloride tablets, follow the suspension preparation instructions below to administer benazepril hydrochloride as a suspension.

Treatment with benazepril hydrochloride tablets is not advised for children below the age of 6 years (see PRECAUTIONS: Pediatric Use) and in pediatric patients with glomerular filtration rate < 30 mL, as there are insufficient data available to support a dosing recommendation in these groups.

For Hypertensive Patients with Renal Impairment

For patients with a creatinine clearance < 30 mL/min/1.73 m2 (serum creatinine > 3 mg/dL), the recommended initial dose is 5 mg benazepril hydrochloride tablets once daily. Dosage may be titrated upward until blood pressure is controlled or to a maximum total daily dose of 40 mg (see WARNINGS).

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 2 minutes. Allow the suspension to stand for a minimum of one 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.
Azathioprine

Azathioprine

TPMT TESTING CANNOT SUBSTITUTE FOR COMPLETE BLOOD COUNT (CBC) MONITORING IN PATIENTS RECEIVING AZATHIOPRINE TABLETS. TPMT genotyping or phenotyping can be used to identify patients with absent or reduced TPMT activity. Patients with low or absent TPMT activity are at an increased risk of developing severe, life threatening myelotoxicity from azathioprine tablets if conventional doses are given. Physicians may consider alternative therapies for patients who have low or absent TPMT activity (homozygous for nonfunctional alleles). Azathioprine tablets should be administered with caution to patients having one nonfunctional allele (heterozygous) who are at risk for reduced TPMT activity that may lead to toxicity if conventional doses are given. Dosage reduction is recommended in patients with reduced TPMT activity. Early drug discontinuation may be considered in patients with abnormal CBC results that do not respond to dose reduction.

Renal Homotransplantation

The dose of azathioprine tablets required to prevent rejection and minimize toxicity will vary with individual patients; this necessitates careful management. The initial dose is usually 3 to 5 mg/kg daily, beginning at the time of transplant. Azathioprine tablets are usually given as a single daily dose on the day of, and in a minority of cases 1 to 3 days before, transplantation. Azathioprine tablets are often initiated with the intravenous administration of the sodium salt, with subsequent use of tablets (at the same dose level) after the postoperative period. Intravenous administration of the sodium salt is indicated only in patients unable to tolerate oral medications. Dose reduction to maintenance levels of 1 to 3 mg/kg daily is usually possible. The dose of azathioprine tablets should not be increased to toxic levels because of threatened rejection. Discontinuation may be necessary for severe hematologic or other toxicity, even if rejection of the homograft may be a consequence of drug withdrawal.

Rheumatoid Arthritis

Azathioprine tablets are usually given on a daily basis. The initial dose should be approximately 1 mg/kg (50 mg to 100 mg) given as a single dose or on a twice daily schedule. The dose may be increased, beginning at 6 to 8 weeks and thereafter by steps at 4-week intervals, if there are no serious toxicities and if initial response is unsatisfactory. Dose increments should be 0.5 mg/kg daily, up to a maximum dose of 2.5 mg/kg per day. Therapeutic response occurs after several weeks of treatment, usually 6 to 8; an adequate trial should be a minimum of 12 weeks. Patients not improved after 12 weeks can be considered refractory. Azathioprine tablets may be continued long-term in patients with clinical response, but patients should be monitored carefully, and gradual dosage reduction should be attempted to reduce risk of toxicities.

Maintenance therapy should be at the lowest effective dose, and the dose given can be lowered decrementally with changes of 0.5 mg/kg or approximately 25 mg daily every 4 weeks while other therapy is kept constant. The optimum duration of maintenance azathioprine tablets has not been determined. Azathioprine tablets can be discontinued abruptly, but delayed effects are possible.

Use in Renal Dysfunction

Relatively oliguric patients, especially those with tubular necrosis in the immediate postcadaveric transplant period, may have delayed clearance of azathioprine tablets or its metabolites, may be particularly sensitive to this drug, and are usually given lower doses.
Dandruff

Dandruff

The optimum daily dosage of carbidopa and levodopa tablets must be determined by careful titration in each patient. Carbidopa and levodopa tablets are available in a 1:4 ratio of carbidopa to levodopa (carbidopa and levodopa tablets 25 mg/100 mg) as well as 1:10 ratio (carbidopa and levodopa tablets 25 mg/250 mg and carbidopa and levodopa tablets 10 mg/100 mg). Tablets of the two ratios may be given separately or combined as needed to provide the optimum dosage.

Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 mg to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.

Usual Initial Dosage

Dosage is best initiated with one tablet of carbidopa and levodopa 25 mg/100 mg 3 times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of carbidopa and levodopa 25 mg/100 mg a day is reached.

If carbidopa and levodopa 10 mg/100 mg is used, dosage may be initiated with one tablet 3 or 4 times a day. However, this will not provide an adequate amount of carbidopa for many patients. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (two tablets q.i.d.) is reached.

How to Transfer Patients from Levodopa

Levodopa must be discontinued at least 12 hours before starting carbidopa and levodopa tablets. A daily dosage of carbidopa and levodopa should be chosen that will provide approximately 25% of the previous levodopa dosage. Patients who are taking less than 1500 mg of levodopa a day should be started on one tablet of carbidopa and levodopa 25 mg/100 mg 3 or 4 times a day. The suggested starting dosage for most patients taking more than 1500 mg of levodopa is one tablet of carbidopa and levodopa 25 mg/250 mg 3 or 4 times a day.

Maintenance

Therapy should be individualized and adjusted according to the desired therapeutic response. At least 70 mg to 100 mg of carbidopa per day should be provided. When a greater proportion of carbidopa is required, one tablet of carbidopa and levodopa 25 mg/100 mg may be substituted for each tablet of carbidopa and levodopa 10 mg/100 mg. When more levodopa is required, carbidopa and levodopa 25 mg/250 mg should be substituted for carbidopa and levodopa 25 mg/100 mg or carbidopa and levodopa 10 mg/100 mg. If necessary, the dosage of carbidopa and levodopa 25 mg/250 mg may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.

Because both therapeutic and adverse responses occur more rapidly with carbidopa and levodopa than with levodopa alone, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly with carbidopa and levodopa than with levodopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.

Addition of Other Antiparkinsonian Medications

Standard drugs for Parkinson's disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa tablets are being administered, although dosage adjustments may be required.

Interruption of Therapy

Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa and levodopa. Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa and levodopa is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)

If general anesthesia is required, carbidopa and levodopa tablets may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS and the usual daily dosage may be administered as soon as the patient is able to take oral medication.
Bupropion Hydrochloride...

Bupropion Hydrochloride

General Dosing Considerations

It is particularly important to administer bupropion hydrochloride tablets in a manner most likely to minimize the risk of seizure (see WARNINGS). Increases in dose should not exceed 100 mg/day in a 3-day period. Gradual escalation in dosage is also important if agitation, motor restlessness, and insomnia, often seen during the initial days of treatment, are to be minimized. If necessary, these effects may be managed by temporary reduction of dose or the short-term administration of an intermediate to long-acting sedative hypnotic. A sedative hypnotic usually is not required beyond the first week of treatment. Insomnia may also be minimized by avoiding bedtime doses. If distressing, untoward effects supervene, dose escalation should be stopped.

No single-dose of bupropion hydrochloride tablets should exceed 150 mg. Bupropion hydrochloride tablets should be administered 3 times daily, preferably with at least 6 hours between successive doses.

Usual Dosage for Adults

The usual adult dose is 300 mg/day, given 3 times daily. Dosing should begin at 200 mg/day, given as 100 mg twice daily. Based on clinical response, this dose may be increased to 300 mg/day, given as 100 mg 3 times daily, no sooner than 3 days after beginning therapy (see Table 3).
Table 3. Dosing Regimen
TreatmentDay

TotalDaily Dose

TabletStrength

Number of Tablets

Morning

Midday

Evening

1

200 mg

100 mg

1

0

1

4

300 mg

100 mg

1

1

1

Increasing the Dosage Above 300 mg/day

As with other antidepressants, the full antidepressant effect of bupropion hydrochloride tablets may not be evident until 4 weeks of treatment or longer. An increase in dosage, up to a maximum of 450 mg/day, given in divided doses of not more than 150 mg each, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg/day. Dosing above 300 mg/day may be accomplished using the 75 mg or 100 mg tablets. The 100 mg tablet must be administered 4 times daily with at least 4 hours between successive doses, in order not to exceed the limit of 150 mg in a single-dose. Bupropion hydrochloride tablets should be discontinued in patients who do not demonstrate an adequate response after an appropriate period of treatment at 450 mg/day.

Maintenance Treatment

The lowest dose that maintains remission is recommended. Although it is not known how long the patient should remain on bupropion hydrochloride tablets, it is generally recognized that acute episodes of depression require several months or longer of antidepressant drug treatment.

Dosage Adjustment for Patients with Impaired Hepatic Function

Bupropion hydrochloride tablets should be used with extreme caution in patients with severe hepatic cirrhosis. The dose should not exceed 75 mg once a day in these patients. Bupropion hydrochloride tablets should be used with caution in patients with hepatic impairment (including mild to moderate hepatic cirrhosis) and a reduced frequency and/or dose should be considered in patients with mild to moderate hepatic cirrhosis (see CLINICAL PHARMACOLOGY, WARNINGS and PRECAUTIONS).

Dosage Adjustment for Patients with Impaired Renal Function

Bupropion hydrochloride tablets should be used with caution in patients with renal impairment and a reduced frequency and/or dose should be considered (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with bupropion hydrochloride tablets. Conversely, at least 14 days should be allowed after stopping bupropion hydrochloride tablets before starting an MAOI antidepressant (see CONTRAINDICATIONS and DRUG INTERACTIONS).

Use of Bupropion Hydrochloride Tablets with Reversible MAOIs such as Linezolid or Methylene Blue

Do not start bupropion hydrochloride tablets in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered (see CONTRAINDICATIONS and DRUG INTERACTIONS).

In some cases, a patient already receiving therapy with bupropion hydrochloride 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 hypertensive reactions in a particular patient, bupropion hydrochloride tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with bupropion hydrochloride tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

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 bupropion hydrochloride tablets is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use (see CONTRAINDICATIONS and DRUG INTERACTIONS).
Bupropion Hydrochloride...

Bupropion Hydrochloride

2.1 General Instructions for Use

To minimize the risk of seizure, increase the dose gradually [see Warnings and Precautions (5.3)]. Bupropion hydrochloride extended-release tablets (SR) should be swallowed whole and not crushed, divided, or chewed. Bupropion hydrochloride extended-release tablets (SR) may be taken with or without food.

The usual adult target dose for bupropion hydrochloride extended-release tablets (SR)is 300 mg per day, given as 150 mg twice daily. Initiate dosing with 150 mg per day given as a single daily dose in the morning. After 3 days of dosing, the dose may be increased to the 300 mg per day target dose, given as 150 mg twice daily. There should be an interval of at least 8 hours between successive doses. A maximum of 400 mg per day, given as 200 mg twice daily, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg per day. To avoid high peak concentrations of bupropion and/or its metabolites, do not exceed 200 mg in any single dose.

It is generally agreed that acute episodes of depression require several months or longer of antidepressant drug treatment beyond the response in the acute episode. It is unknown whether the dose of bupropion hydrochloride extended-release tablets (SR) needed for maintenance treatment is identical to the dose that provided an initial response. Periodically reassess the need for maintenance treatment and the appropriate dose for such treatment.

2.2 Dose Adjustment in Patients with Hepatic Impairment

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of bupropion hydrochloride extended-release tablets (SR) is 100 mg per day or 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.3 Dose Adjustment in Patients with Renal Impairment

Consider reducing the dose and/or frequency of bupropion hydrochloride extended-release tablets (SR) in patients with renal impairment (Glomerular Filtration Rate < 90 mL/min) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.4 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with bupropion hydrochloride extended-release tablets (SR). Conversely, at least 14 days should be allowed after stopping bupropion hydrochloride extended-release tablets (SR) before starting an MAOI antidepressant [see Contraindications (4) and Drug Interactions (7.6)].

2.5 Use of Bupropion Hydrochloride Extended-release Tablets (SR) with Reversible MAOIs Such as Linezolid or Methylene Blue

Do not start bupropion hydrochloride extended-release tablets (SR) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered [see Contraindications (4) and Drug Interactions (7.6)].

In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release tablets (SR) 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 hypertensive reactions in a particular patient, bupropion hydrochloride extended-release tablets (SR) should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with bupropion hydrochloride extended-release tablets (SR) may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

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 bupropion hydrochloride extended-release tablets (SR) is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see Contraindications (4) and Drug Interactions (7.6)].
Neutrogena Complete Acn...

Neutrogena Complete Acne Therapy Solution

The initial recommended dose of tolterodine tartrate tablets is 2 mg twice daily. The dose may be lowered to 1 mg twice daily based on individual response and tolerability. For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose of tolterodine tartrate tablets is 1 mg twice daily (see PRECAUTIONS: General, PRECAUTIONS: Reduced Hepatic and Renal Function, and PRECAUTIONS: Drug Interactions).
Sertraline Hydrochlorid...

Sertraline Hydrochloride

Initial Treatment

Dosage for Adults

Major Depressive Disorder and Obsessive-Compulsive Disorder

Sertraline tablet treatment should be administered at a dose of 50 mg once daily.

Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder

Sertraline tablet 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 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, dose changes should not occur at intervals of less than one week.

Premenstrual Dysphoric Disorder

Sertraline tablet 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 PHARMACOLOGY: Clinical Trials). 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 3 days should be utilized at the beginning of each luteal phase dosing period.

Sertraline tablets should be administered once daily, either in the morning or evening.

Dosage for Pediatric Population (Children and Adolescents)

Obsessive-Compulsive Disorder

Sertraline tablet 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 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, dose changes should not occur at intervals of less than one week.

Sertraline 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 tablets 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 PHARMACOLOGY: Clinical Trials). It is not known whether the dose of sertraline 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 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 PHARMACOLOGY: Clinical Trials). It is not known whether the dose of sertraline 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 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 PHARMACOLOGY: Clinical Trials). 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 tablets for periods of up to 28 weeks in patients with OCD and panic disorder who have responded while taking sertraline 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 PHARMACOLOGY: Clinical Trials). It is not known whether the dose of sertraline 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 in long-term use, that is, for more than three 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 vs. 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 Patients 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 tablets. Conversely, at least 14 days should be allowed after stopping sertraline tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Sertraline Tablets with other MAOIs such as Linezolid or Methylene Blue

Do not start sertraline 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 tablet 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 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 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 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 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 during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Discontinuation of Treatment with Sertraline Tablets

Symptoms associated with discontinuation of sertraline 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.
Captopril

Captopril

Captopril tablets should be taken one hour before meals. Dosage must be individualized.

Hypertension

Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure elevation, salt restriction, and other clinical circumstances. If possible, discontinue the patient's previous antihypertensive drug regimen for one week before starting captopril tablets.

The initial dose of captopril tablets is 25 mg bid or tid. If satisfactory reduction of blood pressure has not been achieved after 1 or 2 weeks, the dose may be increased to 50 mg bid or tid. Concomitant sodium restriction may be beneficial when captopril tablets are used alone.

The dose of captopril tablets in hypertension usually does not exceed 50 mg tid. Therefore, if the blood pressure has not been satisfactorily controlled after 1 to 2 weeks at this dose, (and the patient is not already receiving a diuretic), a modest dose of a thiazide-type diuretic (e.g., hydrochlorothiazide, 25 mg daily), should be added. The diuretic dose may be increased at 1- to 2-week intervals until its highest usual antihypertensive dose is reached.

If captopril tablets are being started in a patient already receiving a diuretic, captopril tablet therapy should be initiated under close medical supervision (see WARNINGS and PRECAUTIONS: Drug Interactions regarding hypotension), with dosage and titration of captopril as noted above.

If further blood pressure reduction is required, the dose of captopril tablets may be increased to 100 mg bid or tid and then, if necessary, to 150 mg bid or tid (while continuing the diuretic). The usual dose range is 25 mg to 150 mg bid or tid. A maximum daily dose of 450 mg captopril tablets should not be exceeded.

For patients with severe hypertension (e.g., accelerated or malignant hypertension), when temporary discontinuation of current antihypertensive therapy is not practical or desirable, or when prompt titration to more normotensive blood pressure levels is indicated, diuretic should be continued but other current antihypertensive medication stopped and captopril tablet dosage promptly initiated at 25 mg bid or tid, under close medical supervision.

When necessitated by the patient’s clinical condition, the daily dose of captopril tablets may be increased every 24 hours or less under continuous medical supervision until a satisfactory blood pressure response is obtained or the maximum dose of captopril tablets is reached. In this regimen, addition of a more potent diuretic, e.g., furosemide, may also be indicated.

Beta-blockers may also be used in conjunction with captopril tablet therapy (see PRECAUTIONS: Drug Interactions), but the effects of the two drugs are less than additive.

Heart Failure

Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe salt/volume depletion. In patients with either normal or low blood pressure, who have been vigorously treated with diuretics and who may be hyponatremic and/or hypovolemic, a starting dose of 6.25 mg or 12.5 mg tid may minimize the magnitude or duration of the hypotensive effect (see WARNINGS: Hypotension); for these patients, titration to the usual daily dosage can then occur within the next several days.

For most patients the usual initial daily dosage is 25 mg tid. After a dose of 50 mg tid is reached, further increases in dosage should be delayed, where possible, for at least 2 weeks to determine if a satisfactory response occurs. Most patients studied have had a satisfactory clinical improvement at 50 mg or 100 mg tid. A maximum daily dose of 450 mg of captopril tablets should not be exceeded.

Captopril tablets should generally be used in conjunction with a diuretic and digitalis. Captopril tablet therapy must be initiated under very close medical supervision.

Left Ventricular Dysfunction After Myocardial Infarction

The recommended dose for long-term use in patients following a myocardial infarction is a target maintenance dose of 50 mg tid.

Therapy may be initiated as early as 3 days following a myocardial infarction. After a single dose of 6.25 mg, captopril tablet therapy should be initiated at 12.5 mg tid. Captopril tablets should then be increased to 25 mg tid during the next several days and to a target dose of 50 mg tid over the next several weeks as tolerated (see CLINICAL PHARMACOLOGY).

Captopril tablets may be used in patients treated with other post-myocardial infarction therapies, e.g., thrombolytics, aspirin, beta-blockers.

Diabetic Nephropathy

The recommended dose of captopril tablets for long-term use to treat diabetic nephropathy is 25 mg tid.

Other antihypertensives such as diuretics, beta-blockers, centrally acting agents or vasodilators may be used in conjunction with captopril tablets if additional therapy is required to further lower blood pressure.

Dosage Adjustment in Renal Impairment

Because captopril is excreted primarily by the kidneys, excretion rates are reduced in patients with impaired renal function. These patients will take longer to reach steady-state captopril levels and will reach higher steady-state levels for a given daily dose than patients with normal renal function. Therefore, these patients may respond to smaller or less frequent doses.

Accordingly, for patients with significant renal impairment, initial daily dosage of captopril tablets should be reduced, and smaller increments utilized for titration, which should be quite slow (1- to 2-week intervals). After the desired therapeutic effect has been achieved, the dose should be slowly back-titrated to determine the minimal effective dose. When concomitant diuretic therapy is required, a loop diuretic (e.g., furosemide), rather than a thiazide diuretic, is preferred in patients with severe renal impairment (see WARNINGS: Anaphylactoid Reactions During Membrane Exposure and PRECAUTIONS: Hemodialysis).
Carbidopa And Levodopa

Carbidopa And Levodopa

Carbidopa and levodopa extended-release tablets contain carbidopa and levodopa in a 1:4 ratio as either the 50 mg/200 mg tablet or the 25 mg/100 mg tablet. The daily dosage of carbidopa and levodopa extended-release tablets must be determined by careful titration. Patients should be monitored closely during the dose adjustment period, particularly with regard to appearance or worsening of involuntary movements, dyskinesias or nausea. Carbidopa and levodopa extended-release tablets should not be chewed or crushed.

Standard drugs for Parkinson’s disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa extended-release tablets are being administered, although their dosage may have to be adjusted.

Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, carbidopa and levodopa extended-release tablets can be given to patients receiving supplemental pyridoxine (vitamin B6).

Initial Dosage

Patients Currently Treated with Conventional Carbidopa-Levodopa Preparations

Studies show that peripheral dopa-decarboxylase is saturated by the bioavailable carbidopa at doses of 70 mg a day and greater. Because the bioavailabilities of carbidopa and levodopa in carbidopa and levodopa immediate-release tablets and carbidopa and levodopa extended-release tablets are different, appropriate adjustments should be made, as shown in Table 2.
Table 2: Approximate Bioavailabilities at Steady-State* * This table is only a guide to bioavailabilities since other factors such as food, drugs, and inter-patient variabilities may affect the bioavailability of carbidopa and levodopa. † The extent of availability of levodopa from carbidopa and levodopa extended-release tablets was about 70% to 75% relative to intravenous levodopa or standard carbidopa and levodopa immediate-release tablets in the elderly. ‡ The extent of availability of levodopa from carbidopa and levodopa immediate-release tablets was 99% relative to intravenous levodopa in the healthy elderly.
Tablet

Amount of Levodopa (mg) in Each Tablet

Approximate Bioavailability

Approximate Amount of Bioavailable Levodopa (mg) in Each Tablet

Carbidopa and LevodopaExtended-release Tablets50 mg/200 mg

200

0.70 to 0.75†

140 to 150

Carbidopa and LevodopaImmediate-release Tablets25 mg/100 mg

100

0.99‡

99

Dosage with carbidopa and levodopa extended-release tablets should be substituted at an amount that provides approximately 10% more levodopa per day, although this may need to be increased to a dosage that provides up to 30% more levodopa per day depending on clinical response (see DOSAGE AND ADMINISTRATION: Titration with Carbidopa and Levodopa Extended-release Tablets). The interval between doses of carbidopa and levodopa extended-release tablets should be 4 to 8 hours during the waking day (see CLINICAL PHARMACOLOGY: Pharmacodynamics).

A guideline for initiation of carbidopa and levodopa extended-release tablets is shown in Table 3.
Table 3: Guidelines for Initial Conversion from Carbidopa and Levodopa Immediate-release Tablets to Carbidopa and Levodopa Extended-release Tablets * For dosing ranges not shown in the table see DOSAGE AND ADMINISTRATION: Initial Dosage: Patients Currently Treated with Conventional Carbidopa and Levodopa Preparations.
Carbidopa and Levodopa Immediate-release Tablets

Carbidopa and Levodopa Extended-release Tablets

Total Daily Dose* Levodopa (mg)

Suggested Dosage Regimen

300–400

200 mg b.i.d.

500–600

300 mg b.i.d. or200 mg t.i.d.

700–800

A total of 800 mg in 3 or more divided doses (e.g., 300 mg a.m., 300 mg early p.m. and 200 mg later p.m.)

900–1000

A total of 1000 mg in 3 or more divided doses (e.g., 400 mg a.m., 400 mg early p.m., and 200 mg later p.m.)

Patients Currently Treated with Levodopa Without a Decarboxylase Inhibitor

Levodopa must be discontinued at least 12 hours before therapy with carbidopa and levodopa extended-release tablets is started. Carbidopa and levodopa extended-release tablets should be substituted at a dosage that will provide approximately 25% of the previous levodopa dosage. In patients with mild to moderate disease, the initial dose is usually one tablet of 50 mg/200 mg carbidopa and levodopa extended-release tablets b.i.d.

Patients Not Receiving Levodopa

In patients with mild to moderate disease, the initial recommended dose is one tablet of 50 mg/200 mg carbidopa and levodopa extended-release tablets b.i.d. Initial dosage should not be given at intervals of less than 6 hours.

Titration with Carbidopa and Levodopa Extended-release Tablets

Following initiation of therapy, doses and dosing intervals may be increased or decreased depending upon therapeutic response. Most patients have been adequately treated with doses of carbidopa and levodopa extended-release tablets that provide 400 mg to 1600 mg of levodopa per day, administered as divided doses at intervals ranging from 4 to 8 hours during the waking day. Higher doses of carbidopa and levodopa extended-release tablets (2400 mg or more of levodopa per day) and shorter intervals (less than 4 hours) have been used, but are not usually recommended.

When doses of carbidopa and levodopa extended-release tablets are given at intervals of less than 4 hours, and/or if the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day.

An interval of at least 3 days between dosage adjustments is recommended.

Maintenance

Because Parkinson's disease is progressive, periodic clinical evaluations are recommended; adjustment of the dosage regimen of carbidopa and levodopa extended-release tablets may be required.

Addition of Other Antiparkinson Medications

Anticholinergic agents, dopamine agonists, and amantadine can be given with carbidopa and levodopa extended-release tablets. Dosage adjustment of carbidopa and levodopa extended-release tablets may be necessary when these agents are added.

A dose of carbidopa and levodopa immediate-release tablets 25 mg/100 mg or 10 mg/100 mg (one half or a whole tablet) can be added to the dosage regimen of carbidopa and levodopa extended-release tablets in selected patients with advanced disease who need additional immediate-release levodopa for a brief time during daytime hours.

Interruption of Therapy

Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa and levodopa immediate-release tablets or carbidopa and levodopa extended-release tablets.

Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa and levodopa extended-release tablets is required, especially if the patient is receiving neuroleptics (see WARNINGS).

If general anesthesia is required, carbidopa and levodopa extended-release tablets may be continued as long as the patient is permitted to take oral medication. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual dosage should be administered as soon as the patient is able to take oral medication.
Ciprofloxacin

Ciprofloxacin

Adults

Ciprofloxacin tablets should be administered orally to adults as described in the Dosage Guidelines table.

The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient’s host-defense mechanisms, and the status of renal function and hepatic function.

The duration of treatment depends upon the severity of infection. The usual duration is 7 to 14 days; however, for severe and complicated infections more prolonged therapy may be required. Ciprofloxacin should be administered at least 2 hours before or 6 hours after magnesium/aluminum antacids, polymeric phosphate binders (e.g., 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.
ADULT DOSAGE GUIDELINES * 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). † used in conjunction with metronidazole ‡ Drug administration should begin as soon as possible after suspected or confirmed exposure. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit. 6 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX: Additional Information.
Infection

Severity

Dose

Frequency

Usual Durations*

Urinary Tract

Acute Uncomplicated

250 mg

q 12 h

3 Days

Mild/Moderate

250 mg

q 12 h

7 to 14 Days

Severe/Complicated

500 mg

q 12 h

7 to 14 Days

Chronic Bacterial Prostatitis

Mild/Moderate

500 mg

q 12 h

28 Days

Lower Respiratory Tract

Mild/Moderate

500 mg

q 12 h

7 to 14 Days

Severe/Complicated

750 mg

q 12 h

7 to 14 Days

Acute Sinusitis

Mild/Moderate

500 mg

q 12 h

10 Days

Skin and Skin Structure

Mild/Moderate

500 mg

q 12 h

7 to 14 Days

Severe/Complicated

750 mg

q 12 h

7 to 14 Days

Bone and Joint

Mild/Moderate

500 mg

q 12 h

≥ 4 to 6 Weeks

Severe/Complicated

750 mg

q 12 h

≥ 4 to 6 Weeks

Intra-Abdominal†

Complicated

500 mg

q 12 h

7 to 14 Days

Infectious Diarrhea

Mild/Moderate/Severe

500 mg

q 12 h

5 to 7 Days

Typhoid Fever

Mild/Moderate

500 mg

q 12 h

10 Days

Urethral and Cervical Gonococcal Infections

Uncomplicated

250 mg

Single Dose

Single Dose

Inhalational Anthrax (post-exposure)‡

500 mg

q 12 h

60 Days

Conversion of I.V. to Oral Dosing in Adults

Patients whose therapy is started with ciprofloxacin I.V. may be switched to ciprofloxacin tablets when clinically indicated at the discretion of the physician. (See CLINICAL PHARMACOLOGY and table below for the equivalent dosing regimens.)
Equivalent AUC Dosing Regimens
Ciprofloxacin Oral Dosage

Equivalent Ciprofloxacin I.V. Dosage

250 mg Tablet q 12 h

200 mg I.V. q 12 h

500 mg Tablet q 12 h

400 mg I.V. q 12 h

750 mg Tablet q 12 h

400 mg I.V. q 8 h

Adults with Impaired Renal Function

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. The following table provides dosage guidelines for use in patients with renal impairment:
RECOMMENDED STARTING AND MAINTENANCE DOSES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION
Creatinine Clearance (mL/min)

Dose

> 50

See Usual Dosage.

30 to 50

250 mg to 500 mg q 12 h

5 to 29

250 mg to 500 mg q 18 h

Patients on hemodialysis orPeritoneal dialysis

250 mg to 500 mg q 24 h(after dialysis)

When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance.

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.

Pediatrics

Ciprofloxacin tablets should be administered orally as described in the Dosage Guidelines table. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed. (See ADVERSE REACTIONS and CLINICAL STUDIES.)

Dosing and initial route of therapy (i.e., I.V. or oral) for complicated urinary tract infection or pyelonephritis should be determined by the severity of the infection. In the clinical trial, pediatric patients with moderate to severe infection were initiated on 6 to 10 mg/kg I.V. every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician.
PEDIATRIC DOSAGE GUIDELINES * The total duration of therapy for complicated urinary tract infection and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). † Drug administration should begin as soon as possible after suspected or confirmed exposure to Bacillus anthracis spores. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit. 6 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX IN ADULTS AND PEDIATRICS: Additional Information.
Infection

Route of Administration

Dose (mg/kg)

Frequency

Total Duration

Complicated Urinary Tract or Pyelonephritis

Intravenous

6 to 10 mg/kg (maximum 400 mg per dose; not to be exceeded even in patients weighing > 51 kg)

Every 8 hours

10 to 21 days*

(patients from 1 to 17 years of age)

Oral

10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceeded even in patients weighing > 51 kg)

Every 12 hours

Inhalational Anthrax (Post-Exposure)†

Intravenous

10 mg/kg (maximum 400 mg per dose)

Every 12 hours

60 days

Oral

15 mg/kg (maximum 500 mg per dose)

Every 12 hours

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

Chlordiazepoxide Hydrochloride

Because of the wide range of clinical indications for chlordiazepoxide HCl, the optimum dosage varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects.

ADULTS

USUAL DAILY DOSE

Relief of Mild and Moderate Anxiety Disorders and Symptoms of Anxiety

5 mg or 10 mg, 3 or 4 times daily

Relief of Severe Anxiety Disorders and Symptoms of Anxiety

20 mg or 25 mg, 3 or 4 times daily

Geriatric Patients, or in the presence of

debilitating disease.

5 mg, 2 to 4 times daily

Preoperative Apprehension and Anxiety

On days preceding surgery, 5 to 10 mg orally, 3 or 4 times daily. If used as preoperative medication, 50 to 100 mg IM* 1 hour prior to surgery.

PEDIATRIC PATIENTS

USUAL DAILY DOSE

Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required. Since clinical experience in pediatric patients under 6 years of age is limited, the use of the drug in this age group is not recommended.

5 mg, 2 to 4 times daily (may be increased in some pediatric patients to 10 mg, 2 to 3 times daily)

For the relief of withdrawal symptoms of acute alcoholism, the parenteral form* is usually used initially. If the drug is administered orally, the suggested initial dose is 50 to 100 mg, to be followed by repeated doses as needed until agitation is controlled — up to 300 mg per day. Dosage should then be reduced to maintenance levels.

*See package insert for Injectable Chlordiazepoxide HCl.
Menstrual Relief Maximu...

Menstrual Relief Maximum Strength

Trichomoniasis In the Female One-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 Male

Treatment should be individualized as it is for the female.

Amebiasis

Adults

For 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 patients

35 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 (approx. 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 Adjustments

Patients with Severe Hepatic Impairment

For patients with severe hepatic

impairment (Child-Pugh C), the dose of metronidazole should be reduced by 50% (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Patients Undergoing Hemodialysis:

Hemodialysis 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).
Clozapine

Clozapine

Switching from a Previous Antipsychotic Therapy to Clozapine

It is generally recommended that clozapine tablets should not be used in combination with other antipsychotics. When clozapine tablet therapy is to be initiated in a patient undergoing oral antipsychotic therapy, it is recommended that the dosage of other antipsychotics be reduced or discontinued by gradually tapering it downwards. Based on the clinical circumstances, the prescribing physician should judge whether or not to discontinue the other antipsychotic therapy before initiating treatment with clozapine tablets.

Treatment-Resistant Schizophrenia

Upon initiation of clozapine tablet therapy, up to a one week supply of additional clozapine tablets may be provided to the patient to be held for emergencies (e.g., weather, holidays).

Initial Treatment

It is recommended that treatment with clozapine tablets begin with one-half of a 25 mg tablet (12.5 mg) once or twice daily and then be continued with daily dosage increments of 25 to 50 mg/day, if well tolerated, to achieve a target dose of 300 to 450 mg/day by the end of 2 weeks. Subsequent dosage increments should be made no more than once or twice weekly, in increments not to exceed 100 mg. Cautious titration and a divided dosage schedule are necessary to minimize the risks of hypotension, seizure, and sedation.

In the multicenter study that provides primary support for the effectiveness of clozapine in patients resistant to standard drug treatment for schizophrenia, patients were titrated during the first 2 weeks up to a maximum dose of 500 mg/day, on a t.i.d. basis, and were then dosed in a total daily dose range of 100 to 900 mg/day, on a t.i.d. basis thereafter, with clinical response and adverse effects as guides to correct dosing.

Therapeutic Dose Adjustment

Daily dosing should continue on a divided basis as an effective and tolerable dose level is sought. While many patients may respond adequately at doses between 300 to 600 mg/day, it may be necessary to raise the dose to the 600 to 900 mg/day range to obtain an acceptable response. (Note: In the multicenter study providing the primary support for the superiority of clozapine tablets in treatment-resistant patients, the mean and median clozapine tablet doses were both approximately 600 mg/day.)

Because of the possibility of increased adverse reactions at higher doses, particularly seizures, patients should ordinarily be given adequate time to respond to a given dose level before escalation to a higher dose is contemplated. Clozapine tablets can cause EEG changes, including the occurrence of spike and wave complexes. It lowers the seizure threshold in a dose-dependent manner and may induce myoclonic jerks or generalized seizures. These symptoms may be likely to occur with rapid dose increase and in patients with preexisting epilepsy. In this case, the dose should be reduced and, if necessary, anticonvulsant treatment initiated.

Dosing should not exceed 900 mg/day.

Because of the significant risk of agranulocytosis and seizure, events which both present a continuing risk over time, the extended treatment of patients failing to show an acceptable level of clinical response should ordinarily be avoided.

Maintenance Treatment

While the maintenance effectiveness of clozapine in schizophrenia is still under study, the effectiveness of maintenance treatment is well established for many other drugs used to treat schizophrenia. It is recommended that responding patients be continued on clozapine tablets, but at the lowest level needed to maintain remission. Because of the significant risk associated with the use of clozapine tablets, patients should be periodically reassessed to determine the need for maintenance treatment.

Discontinuation of Treatment

In the event of planned termination of clozapine tablet therapy, gradual reduction in dose is recommended over a 1 to 2 week period. However, should a patient’s medical condition require abrupt discontinuation (e.g., leukopenia), the patient should be carefully observed for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound such as headache, nausea, vomiting, and diarrhea (see PRECAUTIONS).

Reinitiation of Treatment in Patients Previously Discontinued

When restarting patients who have had even a brief interval off clozapine tablets, i.e., 2 days or more since the last dose, it is recommended that treatment be reinitiated with one-half of a 25 mg tablet (12.5 mg) once or twice daily (see WARNINGS). If that dose is well tolerated, it may be feasible to titrate patients back to a therapeutic dose more quickly than is recommended for initial treatment. However, any patient who has previously experienced respiratory or cardiac arrest with initial dosing, but was then able to be successfully titrated to a therapeutic dose, should be retitrated with extreme caution after even 24 hours of discontinuation.

Certain additional precautions seem prudent when reinitiating treatment. The mechanisms underlying clozapine induced adverse reactions are unknown. It is conceivable, however, that reexposure of a patient might enhance the risk of an untoward event’s occurrence and increase its severity. Such phenomena, for example, occur when immune mediated mechanisms are responsible. Consequently, during the reinitiation of treatment, additional caution is advised. Patients discontinued for WBC counts below 2000/mm3 or an ANC below 1000/mm3 must not be restarted on clozapine tablets. (See WARNINGS.)

Reducing the Risk of Recurrent Suicidal Behavior in Patients with Schizophrenia or Schizoaffective Disorder

The dosage and administration recommendations outlined above regarding the use of clozapine tablets in patients with treatment-resistant schizophrenia should also be followed when treating patients with schizophrenia or schizoaffective disorder at risk for recurrent suicidal behavior.

The InterSePT study demonstrated the efficacy of clozapine in treatment of patients with schizophrenia or schizoaffective disorder at risk for recurrent suicidal behavior where the mean daily dose was about 300 mg (range 12.5 mg to 900 mg).

Patients previously treated with other antipsychotics were cross-titrated to clozapine tablets over a one-month interval; the dose of the previous antipsychotic was gradually decreased simultaneous with a gradual increase in clozapine tablet dose over the first month of the study. Patients on depot antipsychotic medication began clozapine tablets after one full dosing interval since the last injection.

Recommendations to Reduce the Risk of Recurrent Suicidal Behavior in Patients Who Otherwise Previously Responded to Treatment of Schizophrenia or Schizoaffective Disorder with Another Antipsychotic Medication

The results of the InterSePT study demonstrated that, for a 2-year treatment period, the probability of a suicide attempt or a hospitalization due to imminent suicide risk is stable at approximately 24% after one year of treatment with clozapine tablets (Figure 1 Clinical Trial Data Section). A course of treatment with clozapine tablets of at least 2 years is therefore recommended in order to maintain the reduction of risk for suicidal behavior. After 2 years, it is recommended that the patient’s risk of suicidal behavior be assessed. If the physician’s assessment indicates that a significant risk for suicidal behavior is still present, treatment with clozapine tablets should be continued. Thereafter, the decision to continue treatment with clozapine tablets should be revisited at regular intervals, based on thorough assessments of the patient’s risk for suicidal behavior during treatment. If the physician determines that the patient is no longer at risk for suicidal behavior, treatment with clozapine tablets may be discontinued (see recommendations above regarding discontinuation of treatment) and treatment of the underlying disorder with an antipsychotic medication to which the patient has previously responded may be resumed.
Cyclobenzaprine Hydroch...

Cyclobenzaprine Hydrochloride

For most patients, the recommended dose of cyclobenzaprine hydrochloride tablets is 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 2 or 3 weeks is 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).
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.
Desmopressin Acetate

Desmopressin Acetate

Central Diabetes Insipidus

The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients previously on intranasal desmopressin acetate therapy should begin tablet therapy twelve hours after the last intranasal dose. During the initial dose titration period, patients should be observed closely and appropriate safety parameters measured to assure adequate response. Patients should be monitored at regular intervals during the course of desmopressin acetate tablet therapy to assure adequate antidiuretic response. Modifications in dosage regimen should be implemented as necessary to assure adequate water turnover. Fluid restriction should be observed (see WARNINGS; PRECAUTIONS, Pediatric Use and Geriatric Use).

Adults and Children

It is recommended that patients be started on doses of 0.05 mg (½ of the 0.1 mg tablet) two times a day and individually adjusted to their optimum therapeutic dose. Most patients in clinical trials found that the optimal dosage range is 0.1 mg to 0.8 mg daily, administered in divided doses. Each dose should be separately adjusted for an adequate diurnal rhythm of water turnover. Total daily dosage should be increased or decreased in the range of 0.1 mg to 1.2 mg divided into two or three daily doses as needed to obtain adequate antidiuresis. See Pediatric Use subsection for special considerations when administering desmopressin acetate to pediatric diabetes insipidus patients.

Geriatric Use

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY, HumanPharmacokinetics; CONTRAINDICATIONS; and PRECAUTIONS, Geriatric Use).

Primary Nocturnal Enuresis

The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to response. Patients previously on intranasal desmopressin acetate therapy can begin tablet therapy the night following (24 hours after) the last intranasal dose. The recommended initial dose for patients age 6 years and older is 0.2 mg at bedtime. The dose may be titrated up to 0.6 mg to achieve the desired response. Fluid restriction should be observed, and fluid intake should be limited to a minimum from 1 hour before desmopressin administration, until the next morning, or at least 8 hours after administration (see WARNINGS and PRECAUTIONS, Pediatric Use and Geriatric Use).
Esmolol Hydrochloride

Esmolol Hydrochloride

2.1 Dosing Information

Tizanidine tablets may be prescribed with or without food. Once the formulation has been selected and the decision to take with or without food has been made, this regimen should not be altered.

Food has complex effects on tizanidine pharmacokinetics, which differ with the different formulations. Tizanidine capsules and tizanidine tablets are bioequivalent to each other under fasting conditions (more than 3 hours after a meal), but not under fed conditions (within 30 minutes of a meal). These pharmacokinetic differences may result in clinically significant differences when switching administration of tablet and capsules and when switching administration between the fed or fasted state. These changes may result in increased adverse events, or delayed or more rapid onset of activity, depending upon the nature of the switch. For this reason, the prescriber should be thoroughly familiar with the changes in kinetics associated with these different conditions [see Clinical Pharmacology (12.3)].

The recommended starting dose is 2 mg. Because the effect of tizanidine peaks at approximately 1 to 2 hours post-dose and dissipates between 3 to 6 hours post-dose, treatment can be repeated at 6 to 8 hour intervals, as needed, to a maximum of three doses in 24 hours.

Dosage can be gradually increased by 2 mg to 4 mg at each dose, with 1 to 4 days between dosage increases, until a satisfactory reduction of muscle tone is achieved. The total daily dose should not exceed 36 mg. Single doses greater than 16 mg have not been studied.

2.2 Dosing in Patients with Renal Impairment

Tizanidine tablets should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased [see Warnings and Precautions (5.7)].

2.3 Dosing in Patients with Hepatic Impairment

Tizanidine tablets should be used with caution in patients with any hepatic impairment. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. Monitoring of aminotransferase levels is recommended for baseline and one month after maximum dose is achieved, or if hepatic injury is suspected [see Use in Specific Populations (8.7)].

2.4 Drug Discontinuation

If therapy needs to be discontinued, particularly in patients who have been receiving high doses (20 mg to 36 mg daily) for long periods (9 weeks or more) or who may be on concomitant treatment with narcotics, the dose should be decreased slowly (2 mg to 4 mg per day) to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia [see Drug Abuse and Dependence (9.3)].
Advantage Multi For Dog...

Advantage Multi For Dogs

Oral Dosage

Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.

Initial Dosage for Adults

For outpatients 75 mg of amitriptyline HCl a day in divided doses is usually satisfactory. If necessary, this may be increased to a total of 150 mg per day. Increases are made preferably in the late afternoon and/or bedtime doses. A sedative effect may be apparent before the antidepressant effect is noted, but an adequate therapeutic effect may take as long as 30 days to develop.

An alternate method of initiating therapy in outpatients is to begin with 50 mg to 100 mg amitriptyline HCl at bedtime. This may be increased by 25 mg or 50 mg as necessary in the bedtime dose to a total of 150 mg per day.

Hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg a day if necessary. A small number of hospitalized patients may need as much as 300 mg a day.

Adolescent and Elderly Patients

In general, lower dosages are recommended for these patients. 10 mg three times a day with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages.

Maintenance

The usual maintenance dosage of amitriptyline HCl is 50 mg to 100 mg per day. In some patients 40 mg per day is sufficient. For maintenance therapy the total daily dosage may be given in a single dose preferably at bedtime. When satisfactory improvement has been reached, dosage should be reduced to the lowest amount that will maintain a relief of symptoms. It is appropriate to continue maintenance therapy 3 months or longer, to lessen the possibility of relapse.

Pediatric Use

In view of the lack of experience with the use of this drug in pediatric patients, it is not recommended at the present time for patients under 12 years of age.

Plasma Levels

Because of the wide variation in the absorption and distribution of tricyclic antidepressants in body fluids, it is difficult to directly correlate plasma levels and therapeutic effect. However, determination of plasma levels may be useful in identifying patients who appear to have toxic effects and may have excessively high levels, or those in whom lack of absorption or noncompliance is suspected. Because of increased intestinal transit time and decreased hepatic metabolism in elderly patients, plasma levels are generally higher for a given oral dose of amitriptyline hydrochloride than in younger patients. Elderly patients should be monitored carefully and quantitative serum levels obtained as clinically appropriate. Adjustments in dosage should be made according to the patient’s clinical response and not on the basis of plasma levels.**
Clonazepam

Clonazepam

Clonazepam is available as a tablet. The tablets should be administered with water by swallowing the tablet whole.

Seizure Disorders

Adults

The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 mg to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg.

The use of multiple anticonvulsants may result in an increase of depressant adverse effects. This should be considered before adding clonazepam to an existing anticonvulsant regimen.

Pediatric Patients

Clonazepam is administered orally. In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses. Dosage should be increased by no more than 0.25 mg to 0.5 mg every third day until a daily maintenance dose of 0.1 to 0.2 mg/kg of body weight has been reached, unless seizures are controlled or side effects preclude further increase. Whenever possible, the daily dose should be divided into three equal doses. If doses are not equally divided, the largest dose should be given before retiring.

Geriatric Patients

There is no clinical trial experience with clonazepam in seizure disorder patients 65 years of age and older. In general, elderly patients should be started on low doses of clonazepam and observed closely (see PRECAUTIONS: Geriatric Use).

Panic Disorder

Adults

The initial dose for adults with panic disorder is 0.25 mg bid. An increase to the target dose for most patients of 1 mg/day may be made after 3 days. The recommended dose of 1 mg/day is based on the results from a fixed dose study in which the optimal effect was seen at 1 mg/day. Higher doses of 2, 3 and 4 mg/day in that study were less effective than the 1 mg/day dose and were associated with more adverse effects. Nevertheless, it is possible that some individual patients may benefit from doses of up to a maximum dose of 4 mg/day, and in those instances, the dose may be increased in increments of 0.125 mg to 0.25 mg bid every 3 days until panic disorder is controlled or until side effects make further increases undesired. To reduce the inconvenience of somnolence, administration of one dose at bedtime may be desirable.

Treatment should be discontinued gradually, with a decrease of 0.125 mg bid every 3 days, until the drug is completely withdrawn.

There is no body of evidence available to answer the question of how long the patient treated with clonazepam should remain on it. Therefore, the physician who elects to use clonazepam for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Pediatric Patients

There is no clinical trial experience with clonazepam in panic disorder patients under 18 years of age.

Geriatric Patients

There is no clinical trial experience with clonazepam in panic disorder patients 65 years of age and older. In general, elderly patients should be started on low doses of clonazepam and observed closely (see PRECAUTIONS: Geriatric Use).
Acetaminophen And Codei...

Acetaminophen And Codeine Phosphate

Dosage should be adjusted according to severity of pain and response of the patient.

The usual adult dosage is:

Single Doses (range)

Maximum 24 Hour Dose

Codeine Phosphate

15 mg to 60 mg

360 mg

Acetaminophen

300 mg to 1000 mg

4000 mg

The usual dose of codeine phosphate in children is 0.5 mg/kg.

Doses may be repeated up to every 4 hours.

The prescriber must determine the number of tablets per dose, and the maximum number of tablets per 24 hours based upon the above dosage guidance. This information should be conveyed in the prescription.

It should be kept in mind, however, that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of undesirable side effects. Equivalently high doses in children would have similar effects.
Diltiazem Hydrochloride...

Diltiazem Hydrochloride

Exertional Angina Pectoris Due to Atherosclerotic Coronary Artery Disease or Angina Pectoris at Rest Due to Coronary Artery Spasm

Dosage must be adjusted to each patient's needs. Starting with 30 mg 4 times daily, before meals and at bedtime, dosage should be increased gradually (given in divided doses 3 or 4 times daily) at one-to two-day intervals until optimum response is obtained. Although individual patients may respond to any dosage level, the average optimum dosage range appears to be 180 to 360 mg/day. There are no available data concerning dosage requirements in patients with impaired renal or hepatic function. If the drug must be used in such patients, titration should be carried out with particular caution.

Concomitant Use with Other Cardiovascular Agents

1. Sublingual NTG may be taken as required to abort acute anginal attacks during diltiazem therapy.

2. Prophylactic Nitrate Therapy: Diltiazem may be safely coadministered with short- and long-acting nitrates, but there have been no controlled studies to evaluate the antianginal effectiveness of this combination.

3. Beta-blockers (See WARNINGS and PRECAUTIONS.)
Diclofenac Sodium

Diclofenac Sodium

Carefully consider the potential benefits and risks of diclofenac sodium delayed-release tablets and other treatment options before deciding to use diclofenac sodium delayed-release 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 diclofenac sodium delayed-release tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

For the relief of osteoarthritis, the recommended dosage is 100 to 150 mg/day in divided doses (50 mg b.i.d. or t.i.d., or 75 mg b.i.d.).

For the relief of rheumatoid arthritis, the recommended dosage is 150 to 200 mg/day in divided doses (50 mg t.i.d. or q.i.d., or 75 mg b.i.d.).

For the relief of ankylosing spondylitis, the recommended dosage is 100 to 125 mg/day, administered as 25 mg q.i.d., with an extra 25 mg dose at bedtime if necessary.

Different formulations of diclofenac are not necessarily bioequivalent even if the milligram strength is the same.
Dicyclomine Hydrochlori...

Dicyclomine Hydrochloride Capsule Dicyclomine Hydrochloride

Dosage must be adjusted to individual patient needs.

2.1 Oral Dosage and Administration in Adults

The recommended initial dose is 20 mg 4 times a day.

After one week treatment with the initial dose, the dose may be increased to 40 mg 4 times a day unless side effects limit dosage escalation.

If efficacy is not achieved within 2 weeks or side effects require doses below 80 mg per day, the drug should be discontinued. Documented safety data are not available for doses above 80 mg daily for periods longer than 2 weeks.
Diltiazem Hydrochloride...

Diltiazem Hydrochloride

Hypertensive or anginal patients who are treated with other formulations of diltiazem can safely be switched to diltiazem hydrochloride extended-release capsules (once-a-day dosage) at the nearest equivalent total daily dose. Subsequent titration to higher or lower doses may, however, be necessary and should be initiated as clinically indicated.

Studies have shown a slight increase in the rate of absorption of diltiazem hydrochloride extended-release capsules (once-a-day dosage), when ingested with a high fat breakfast; therefore, administration in the morning on an empty stomach is recommended.

Patients should be cautioned that the diltiazem hydrochloride extended-release capsules should not be opened, chewed or crushed and should be swallowed whole.

Dosage

Hypertension

Dosages must be adjusted to each patient's needs, starting with 180 mg or 240 mg once daily. Based on the antihypertensive effect, the dose may be adjusted as needed. Individual patients, particularly ≥ 60 years of age, may respond to a lower dose of 120 mg. The usual dosage range studied in clinical trials was 180 mg to 480 mg once daily.

Current clinical experience with the 540 mg dose is limited, the dose may be increased to 540 mg with little or no increased risk of adverse reactions. Doses should not exceed 540 mg once daily.

While a dose of diltiazem hydrochloride extended-release capsules given once daily may produce an antihypertensive effect similar to the same total daily dose given in divided doses, individual dose adjustment may be needed.

Angina

Dosages for the treatment of angina should be adjusted to each patient's needs, starting with a dose of 120 mg once daily, which may be titrated to doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7 to 14 day period.

Concomitant Use with Other Cardiovascular Agents

Sublingual Nitroglycerin

Sublingual nitroglycerin may be taken as required to abort acute anginal attacks during diltiazem therapy.

Prophylactic Nitrate Therapy

Diltiazem hydrochloride extended-release capsules (once-a-day dosage) may be safely coadministered with short- and long-acting nitrates.

Beta-Blockers

(See WARNINGS and PRECAUTIONS.)

Antihypertensives

Diltiazem has an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride or the concomitant antihypertensives may need to be adjusted when adding one to the other.
Nifedipine

Nifedipine

Dosage must be adjusted according to each patient’s needs. Therapy for either hypertension or angina should be initiated with 30 mg or 60 mg once daily. Nifedipine extended-release tablets should be swallowed whole and should not be bitten or divided. In general, titration should proceed over a 7 to 14 day period so that the physician can fully assess the response to each dose level and monitor blood pressure before proceeding to higher doses. Since steady-state plasma levels are achieved on the second day of dosing, titration may proceed more rapidly, if symptoms so warrant, provided the patient is assessed frequently. Titration to doses above 120 mg are not recommended.

Angina patients controlled on nifedipine immediate-release capsules alone or in combination with other antianginal medications may be safely switched to nifedipine extended-release tablets at the nearest equivalent total daily dose (e.g., 30 mg t.i.d. of nifedipine immediate-release capsules may be changed to 90 mg once daily of nifedipine extended-release tablets). Subsequent titration to higher or lower doses may be necessary and should be initiated as clinically warranted. Experience with doses greater than 90 mg in patients with angina is limited. Therefore, doses greater than 90 mg should be used with caution and only when clinically warranted.

Avoid coadministration of nifedipine with grapefruit juice (see CLINICAL PHARMACOLOGY and PRECAUTIONS: Other Interactions).

No “rebound effect” has been observed upon discontinuation of nifedipine extended-release tablets. However, if discontinuation of nifedipine is necessary, sound clinical practice suggests that the dosage should be decreased gradually with close physician supervision.

Care should be taken when dispensing nifedipine extended-release tablets to assure that the extended-release dosage form has been prescribed.

Coadministration with Other Antianginal Drugs

Sublingual nitroglycerin may be taken as required for the control of acute manifestations of angina, particularly during nifedipine titration. See PRECAUTIONS: Drug Interactions, for information on coadministration of nifedipine with beta-blockers or long-acting nitrates.
Diltiazem Hydrochloride...

Diltiazem Hydrochloride

Dosages must be adjusted to each patient's needs, starting with 60 to 120 mg twice daily. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, dosage adjustments should be scheduled accordingly. Although individual patients may respond to lower doses, the usual optimum dosage range in clinical trials was 240 to 360 mg/day.

Diltiazem hydrochloride extended-release capsules have an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride extended-release capsules or the concomitant antihypertensives may need to be adjusted when adding one to the other. See WARNINGS and PRECAUTIONS regarding use with beta-blockers.
Plasbumin

Plasbumin

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 mg 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 mg 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)].
Up And Up Antibiotic

Up And Up Antibiotic

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 is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Sucralfate

Sucralfate

Active Duodenal Ulcer

The recommended adult oral dosage for duodenal ulcer is 1 g four times per day on an empty stomach.

Antacids may be prescribed as needed for relief of pain but should not be taken within one-half hour before or after sucralfate.

While healing with sucralfate may occur during the first week or two, treatment should be continued for 4 to 8 weeks unless healing has been demonstrated by x-ray or endoscopic examination.

Maintenance Therapy

The recommended adult oral dosage is 1 g twice a day.

Elderly

In general, dose selection for an elderly patient 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 (see PRECAUTIONS, Geriatric Use).

Call your doctor for medical advice about side effects. You may report side effects to TEVA USA, PHARMACOVIGILANCE at tel: 1-888-838-2872, x6351 or drug.safety@tevapharm.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Metoclopramide

Metoclopramide

Therapy with metoclopramide tablets, USP should not exceed 12 weeks in duration.

For the Relief of Symptomatic Gastroesophageal Reflux

Administer from 10 mg to 15 mg of metoclopramide tablet, USP orally up to q.i.d. 30 minutes before each meal and at bedtime, depending upon symptoms being treated and clinical response (see CLINICAL PHARMACOLOGY and INDICATIONS AND USAGE). If symptoms occur only intermittently or at specific times of the day, use of metoclopramide in single doses up to 20 mg prior to the provoking situation may be preferred rather than continuous treatment. Occasionally, patients (such as elderly patients) who are more sensitive to the therapeutic or adverse effects of metoclopramide will require only 5 mg per dose.

Experience with esophageal erosions and ulcerations is limited, but healing has thus far been documented in one controlled trial using q.i.d. therapy at 15 mg/dose, and this regimen should be used when lesions are present, so long as it is tolerated (see ADVERSE REACTIONS). Because of the poor correlation between symptoms and endoscopic appearance of the esophagus, therapy directed at esophageal lesions is best guided by endoscopic evaluation.

Therapy longer than 12 weeks has not been evaluated and cannot be recommended.

For the Relief of Symptoms Associated With Diabetic Gastroparesis (Diabetic Gastric Stasis)

Administer 10 mg of metoclopramide 30 minutes before each meal and at bedtime for two to eight weeks, depending upon response and the likelihood of continued well-being upon drug discontinuation.

The initial route of administration should be determined by the severity of the presenting symptoms. If only the earliest manifestations of diabetic gastric stasis are present, oral administration of metoclopramide tablets, USP may be initiated. However, if severe symptoms are present, therapy should begin with metoclopramide injection (consult labeling of the injection prior to initiating parenteral administration).

Administration of metoclopramide injection up to 10 days may be required before symptoms subside, at which time oral administration may be instituted. Since diabetic gastric stasis is frequently recurrent, metoclopramide tablet, USP therapy should be reinstituted at the earliest manifestation.

Use in Patients With Renal or Hepatic Impairment

Since metoclopramide is excreted principally through the kidneys, in those patients whose creatinine clearance is below 40 mL/min, therapy should be initiated at approximately one-half the recommended dosage. Depending upon clinical efficacy and safety considerations, the dosage may be increased or decreased as appropriate.

See OVERDOSAGE section for information regarding dialysis.

Metoclopramide undergoes minimal hepatic metabolism, except for simple conjugation. Its safe use has been described in patients with advanced liver disease whose renal function was normal.
Doxazosin

Doxazosin

DOSAGE MUST BE INDIVIDUALIZED. The initial dosage of doxazosin tablets in patients with hypertension and/or BPH is 1 mg given once daily in the a.m. or p.m. This starting dose is intended to minimize the frequency of postural hypotension and first dose syncope associated with doxazosin tablets. Postural effects are most likely to occur between 2 and 6 hours after a dose. Therefore blood pressure measurements should be taken during this time period after the first dose and with each increase in dose. If doxazosin tablet administration is discontinued for several days, therapy should be restarted using the initial dosing regimen.

Concomitant administration of doxazosin tablets with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking doxazosin tablets.

Benign Prostatic Hyperplasia 1 mg to 8 mg Once Daily

The initial dosage of doxazosin tablets is 1 mg, given once daily in the a.m. or p.m. Depending on the individual patient's urodynamics and BPH symptomatology, dosage may then be increased to 2 mg and thereafter to 4 mg and 8 mg once daily, the maximum recommended dose for BPH. The recommended titration interval is 1 to 2 weeks. Blood pressure should be evaluated routinely in these patients.

Hypertension 1 mg to 16 mg Once Daily

The initial dosage of doxazosin tablets is 1 mg given once daily. Depending on the individual patient's standing blood pressure response (based on measurements taken at 2 to 6 hours post-dose and 24 hours post-dose), dosage may then be increased to 2 mg and thereafter if necessary to 4 mg, 8 mg and 16 mg to achieve the desired reduction in blood pressure. Increases in dose beyond 4 mg increase the likelihood of excessive postural effects including syncope, postural dizziness/vertigo and postural hypotension. At a titrated dose of 16 mg once daily the frequency of postural effects is about 12% compared to 3% for placebo.
Finasteride

Finasteride

The recommended dose is 5 mg orally once a day.

Finasteride tablets can be administered alone (see CLINICAL PHARMACOLOGY: Clinical Studies).

Finasteride tablets may be administered with or without meals.

No dosage adjustment is necessary for patients with renal impairment or for the elderly (see CLINICAL PHARMACOLOGY: Pharmacokinetics).
Escitalopram Oxalate

Escitalopram Oxalate

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 3 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 adult 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 reevaluate 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 reevaluate 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)].
Fluvoxamine Maleate

Fluvoxamine Maleate

2.1 Adults

The recommended starting dose for fluvoxamine maleate tablets in adult patients is 50 mg, administered as a single daily dose at bedtime. In the controlled clinical trials establishing the effectiveness of fluvoxamine in OCD, patients were titrated within a dose range of 100 to 300 mg/day. Consequently, the dose should be increased in 50 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved, not to exceed 300 mg per day. It is advisable that a total daily dose of more than 100 mg should be given in two divided doses. If the doses are not equal, the larger dose should be given at bedtime.

2.2 Pediatric Population (children and adolescents)

The recommended starting dose for fluvoxamine maleate tablets in pediatric populations (ages 8 to 17 years) is 25 mg, administered as a single daily dose at bedtime. In a controlled clinical trial establishing the effectiveness of fluvoxamine in OCD, pediatric patients (ages 8 to 17) were titrated within a dose range of 50 to 200 mg/day. Physicians should consider age and gender differences when dosing pediatric patients. The maximum dose in children up to age 11 should not exceed 200 mg/day. Therapeutic effect in female children may be achieved with lower doses. Dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit. The dose should be increased in 25 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved. It is advisable that a total daily dose of more then 50 mg should be given in two divided doses. If the two divided doses are not equal, the larger dose should be given at bedtime.

2.3 Elderly or Hepatically Impaired Patients

Elderly patients and those with hepatic impairment have been observed to have a decreased clearance of fluvoxamine maleate. Consequently, it may be appropriate to modify the initial dose and the subsequent dose titration for these patient groups.

2.4 Pregnant Women during the Third Trimester

Neonates exposed to fluvoxamine maleate tablets and other SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding and may be at risk for persistent pulmonary hypertension of the newborn (PPHN) (see Use in Specific Populations [8.1]). When treating pregnant women with fluvoxamine maleate tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering fluvoxamine maleate tablets in the third trimester.

2.5 Switching Patients to or from a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with fluvoxamine maleate tablets. Similarly, at least 14 days should be allowed after stopping fluvoxamine maleate tablets before starting an MAOI.

2.7 Discontinuation of Treatment with Fluvoxamine Maleate Tablets

Symptoms associated with discontinuation of other SSRIs or SNRIs have been reported (see Warnings and Precautions [5.9]). 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.
Fluphenazine Hydrochlor...

Fluphenazine Hydrochloride

Depending on the severity and duration of symptoms, total daily dosage for adult psychotic patients may range initially from 2.5 mg to 10 mg and should be divided and given at 6 to 8 hour intervals.

The smallest amount that will produce the desired results must be carefully determined for each individual, since optimal dosage levels of this potent drug vary from patient to patient. In general, the oral dose has been found to be approximately 2 to 3 times the parenteral dose of fluphenazine. Treatment is best instituted with a low initial dosage, which may be increased, if necessary, until the desired clinical effects are achieved. Therapeutic effect is often achieved with doses under 20 mg daily. Patients remaining severely disturbed or inadequately controlled may require upward titration of dosage. Daily doses up to 40 mg may be necessary; controlled clinical studies have not been performed to demonstrate safety of prolonged administration of such doses.

When symptoms are controlled, dosage can generally be reduced gradually to daily maintenance doses of 1 mg to 5 mg, often given as a single daily dose. Continued treatment is needed to achieve maximum therapeutic benefits; further adjustments in dosage may be necessary during the course of therapy to meet the patient’s requirements.

For psychotic patients who have been stabilized on a fixed daily dosage of orally administered fluphenazine hydrochloride dosage forms, conversion to the long-acting fluphenazine decanoate may be indicated (see package insert for conversion information).

For geriatric patients, the suggested starting dose is 1 mg to 2.5 mg daily, adjusted according to the response of the patient.
Folic Acid

Folic Acid

Oral administration is preferred. Although most patients with malabsorption cannot absorb food folates, they are able to absorb folic acid given orally. Parenteral administration is not advocated but may be necessary in some individuals (e.g., patients receiving parenteral or enteral alimentation). Doses greater than 0.1 mg should not be used unless anemia due to vitamin B12 deficiency has been ruled out or is being adequately treated with a cobalamin. Daily doses greater than 1 mg do not enhance the hematologic effect, and most of the excess is excreted unchanged in the urine.

The usual therapeutic dosage in adults and children (regardless of age) is up to 1 mg daily. Resistant cases may require larger doses.

When clinical symptoms have subsided and the blood picture has become normal, a daily maintenance level should be used, i.e., 0.1 mg for infants and up to 0.3 mg for children under 4 years of age, 0.4 mg for adults and children 4 or more years of age, and 0.8 mg for pregnant and lactating women, but never less than 0.1 mg/day. Patients should be kept under close supervision and adjustment of the maintenance level made if relapse appears imminent.

In the presence of alcoholism, hemolytic anemia, anticonvulsant therapy, or chronic infection, the maintenance level may need to be increased.
Fenofibrate

Fenofibrate

2.1 General Considerations

Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate tablets and should continue this diet during treatment with fenofibrate tablets. Fenofibrate tablets can be given without regard to meals.

The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy. Physical exercise can be an important ancillary measure. Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy, thiazide diuretics and beta-blockers, are sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia. In such cases, discontinuation of the specific etiologic agent may obviate the need for specific drug therapy of hypertriglyceridemia.

Lipid levels should be monitored periodically and consideration should be given to reducing the dosage of fenofibrate tablets if lipid levels fall significantly below the targeted range.

Therapy should be withdrawn in patients who do not have an adequate response after 2 months of treatment with the maximum recommended dose of 145 mg once daily.

2.2 Primary Hypercholesterolemia or Mixed Dyslipidemia

The initial dose of fenofibrate tablets is 145 mg once daily.

2.3 Severe Hypertriglyceridemia

The initial dose is 48 mg to 145 mg per day. Dosage should be individualized according to patient response and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 145 mg once daily.

2.4 Impaired Renal Function

Treatment with fenofibrate tablets should be initiated at a dose of 48 mg per day in patients having mild to moderately impaired renal function and increased only after evaluation of the effects on renal function and lipid levels at this dose. The use of fenofibrate tablets should be avoided in patients with severe renal impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.5 Geriatric Patients

Dose selection for the elderly should be made on the basis of renal function [see Use in Specific Populations (8.5)].
Doxepin Hydrochloride

Doxepin Hydrochloride

For most patients with illness of mild to moderate severity, a starting daily dose of 75 mg is recommended. Dosage may subsequently be increased or decreased at appropriate intervals and according to individual response. The usual optimum dose range is 75 mg/day to 150 mg/day.

In more severely ill patients higher doses may be required with subsequent gradual increase to 300 mg/day if necessary. Additional therapeutic effect is rarely to be obtained by exceeding a dose of 300 mg/day.

In patients with very mild symptomatology or emotional symptoms accompanying organic disease, lower doses may suffice. Some of these patients have been controlled on doses as low as 25 to 50 mg/day.

The total daily dosage of doxepin (as the hydrochloride) may be given on a divided or once a day dosage schedule. If the once a day schedule is employed the maximum recommended dose is 150 mg/day. This dose may be given at bedtime. The 150 mg capsule strength is intended for maintenance therapy only and is not recommended for initiation of treatment.

Antianxiety effect is apparent before the antidepressant effect. Optimal antidepressant effect may not be evident for 2 to 3 weeks.
Furosemide

Furosemide

Edema

Therapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response.

Adults

The usual initial dose of furosemide is 20 mg to 80 mg given as a single dose. Ordinarily a prompt diuresis ensues. If needed, the same dose can be administered 6 to 8 hours later or the dose may be increased. The dose may be raised by 20 mg to 40 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. The individually determined single dose should then be given once or twice daily (e.g., at 8 am and 2 pm). The dose of furosemide may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states.

Edema may be most efficiently and safely mobilized by giving furosemide on 2 to 4 consecutive days each week.

When doses exceeding 80 mg/day are given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable. (See PRECAUTIONS: Laboratory Tests.)

Geriatric Patients

In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use).

Pediatric Patients

The usual initial dose of oral furosemide in pediatric patients is 2 mg/kg body weight, given as a single dose. If the diuretic response is not satisfactory after the initial dose, dosage may be increased by 1 or 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses greater than 6 mg/kg body weight are not recommended. For maintenance therapy in pediatric patients, the dose should be adjusted to the minimum effective level. For ease of administration, and to allow maximum flexibility in dosing, the use of Furosemide Oral Solution is suggested.

Hypertension

Therapy should be individualized according to the patient's response to gain maximal therapeutic response and to determine the minimal dose needed to maintain the therapeutic response.

Adults

The usual initial dose of furosemide for hypertension is 80 mg, usually divided into 40 mg twice a day. Dosage should then be adjusted according to response. If response is not satisfactory, add other antihypertensive agents.

Changes in blood pressure must be carefully monitored when furosemide is used with other antihypertensive drugs, especially during initial therapy. To prevent excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50 percent when furosemide is added to the regimen. As the blood pressure falls under the potentiating effect of furosemide, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.

Geriatric Patients

In general, dose selection and dose adjustment for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS: Geriatric Use).
Leucovorin Calcium

Leucovorin Calcium

Leucovorin calcium tablets are intended for oral administration. Because absorption is saturable, oral administration of doses greater than 25 mg is not recommended.

Impaired Methotrexate Elimination or Inadvertent Overdosage

Leucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion (see WARNINGS). Leucovorin 15 mg (10 mg/m2) should be administered IM, IV, or PO every 6 hours until serum methotrexate level is less than 10 -8 M. In the presence of gastrointestinal toxicity, nausea, or vomiting, leucovorin should be administered parenterally.

Serum creatinine and methotrexate levels should be determined at 24 hour intervals. If the 24 hour serum creatinine has increased 50% over baseline or if the 24 hour methotrexate level is greater than 5 x 10 -6 M or the 48 hour level is greater than 9 x 10 -7 M, the dose of leucovorin should be increased to 150 mg (100 mg/m2) IV every 3 hours until the methotrexate level is less than 10 -8 M. Doses greater then 25 mg should be given parenterally (see CLINICAL PHARMACOLOGY).

Hydration (3 L/d) and urinary alkalinization with sodium bicarbonate should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7 or greater.

The recommended dose of leucovorin to counteract hematologic toxicity from folic acid antagonists with less affinity for mammalian dihydrofolate reductase than methotrexate (i.e., trimethoprim, pyrimethamine) is substantially less, and 5 to 15 mg of leucovorin per day has been recommended by some investigators.

Patients who experience delayed early methotrexate elimination are likely to develop reversible non-oliguric renal failure. In addition to appropriate leucovorin therapy, these patients require continuing hydration and urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.

Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, leucovorin rescue should be extended for an additional 24 hours (total 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.
Labetalol Hcl

Labetalol Hcl

DOSAGE MUST BE INDIVIDUALIZED. The recommended initial dose is 100 mg twice daily whether used alone or added to a diuretic regimen. After 2 or 3 days, using standing blood pressure as an indicator, dosage may be titrated in increments of 100 mg b.i.d. every 2 or 3 days. The usual maintenance dosage of labetalol hydrochloride tablets is between 200 mg and 400 mg twice daily.

Since the full antihypertensive effect of labetalol hydrochloride tablets is usually seen within the first 1 to 3 hours of the initial dose or dose increment, the assurance of a lack of an exaggerated hypotensive response can be clinically established in the office setting. The antihypertensive effects of continued dosing can be measured at subsequent visits, approximately 12 hours after a dose, to determine whether further titration is necessary.

Patients with severe hypertension may require from 1200 mg to 2400 mg per day, with or without thiazide diuretics. Should side effects (principally nausea or dizziness) occur with these doses administered b.i.d.(twice daily), the same total daily dose administered t.i.d. (three times daily) may improve tolerability and facilitate further titration. Titration increments should not exceed 200 mg b.i.d. (twice daily).

When a diuretic is added, an additive antihypertensive effect can be expected. In some cases this may necessitate a labetalol hydrochloride tablet dosage adjustment. As with most antihypertensive drugs, optimal dosages of labetalol hydrochloride tablets are usually lower in patients also receiving a diuretic.

When transferring a patient from other antihypertensive drugs, labetalol hydrochloride tablets should be introduced as recommended and the dosage of the existing therapy progressively decreased.

Elderly Patients

As in the general patient population, labetalol therapy may be initiated at 100 mg twice daily and titrated upwards in increments of 100 mg b.i.d. as required for control of blood pressure. Since some elderly patients eliminate labetalol more slowly, however, adequate control of blood pressure may be achieved at a lower maintenance dosage compared to the general population. The majority of elderly patients will require between 100 mg and 200 mg b.i.d.
Lice Treatment

Lice Treatment

2.1 Mild to Moderate Active Crohn’s Disease

The recommended adult dosage for the treatment of mild to moderate active Crohn's disease involving the ileum and/or the ascending colon is 9 mg orally taken once daily in the morning for up to 8 weeks. Repeated 8 week courses of budesonide capsules (enteric coated) can be given for recurring episodes of active disease.

2.2 Maintenance of Clinical Remission of Mild to Moderate Crohn’s Disease

Following an 8 week course(s) of treatment for active disease and once the patient’s symptoms are controlled (CDAI less than 150), budesonide capsules (enteric coated) 6 mg orally is recommended once daily for maintenance of clinical remission up to 3 months. If symptom control is still maintained at 3 months an attempt to taper to complete cessation is recommended. Continued treatment with budesonide capsules (enteric coated) 6 mg for more than 3 months has not been shown to provide substantial clinical benefit.

Patients with mild to moderate active Crohn’s disease involving the ileum and/or ascending colon have been switched from oral prednisolone to budesonide capsules (enteric coated) with no reported episodes of adrenal insufficiency. Since prednisolone should not be stopped abruptly, tapering should begin concomitantly with initiating budesonide capsule (enteric coated) treatment.

2.3 CYP3A4 inhibitors

If concomitant administration with ketoconazole, or any other CYP3A4 inhibitor, is indicated, patients should be closely monitored for increased signs and/or symptoms of hypercorticism. Grapefruit juice, which is known to inhibit CYP3A4, should also be avoided when taking budesonide capsules (enteric coated). In these cases, reduction in the dose of budesonide capsules (enteric coated) should be considered [see Drug Interactions (7) and Clinical Pharmacology (12.3)].
Lansoprazole

Lansoprazole

Lansoprazole delayed-release capsules are available as capsules in 15 mg and 30 mg strengths. Directions for use specific to the route and available methods of administration is presented below. Lansoprazole delayed-release capsules should be taken before eating. Lansoprazole delayed-release capsules SHOULD NOT BE CRUSHED OR CHEWED. In the clinical trials, antacids were used concomitantly with lansoprazole.

2.1 Recommended Dose
* Please refer to amoxicillin and clarithromycin full prescribing information for CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly and renally-impaired patients. † Controlled studies did not extend beyond indicated duration. ‡ For patients who do not heal with lansoprazole for 8 weeks (5% to 10%), it may be helpful to give an additional 8 weeks of treatment. If there is a recurrence of erosive esophagitis, an additional 8 week course of lansoprazole may be considered. § The lansoprazole dose was increased (up to 30 mg twice daily) in some pediatric patients after 2 or more weeks of treatment if they remained symptomatic. For pediatric patients unable to swallow an intact capsule please see Administration Options. ¶ Varies with individual patient. Recommended adult starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Dosages up to 90 mg twice daily have been administered. Daily dose of greater than 120 mg should be administered in divided doses. Some patients with Zollinger-Ellison Syndrome have been treated continuously with lansoprazole for more than 4 years.
Indication

Recommended

Frequency

Dose

Duodenal Ulcers

   Short-Term Treatment

15 mg

Once daily for 4 weeks

   Maintenance of Healed

15 mg

Once daily

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence*

     Triple Therapy:

          Lansoprazole Delayed-release Capsules

30 mg

Twice daily (q12h) for 10 or 14 days

          Amoxicillin

1 gram

Twice daily (q12h) for 10 or 14 days

          Clarithromycin

500 mg

Twice daily (q12h) for 10 or 14 days

     Dual Therapy:

          Lansoprazole Delayed-release Capsules

30 mg

Three times daily (q8h) for 14 days

          Amoxicillin

1 gram

Three times daily (q8h) for 14 days

Benign Gastric Ulcer

     Short-Term Treatment

30 mg

Once daily for up to 8 weeks

NSAID-associated Gastric Ulcer

     Healing

30 mg

Once daily for 8 weeks†

     Risk Reduction

15 mg

Once daily for up to 12 weeks†

Gastroesophageal Reflux Disease (GERD)

     Short-Term Treatment of Symptomatic GERD

15 mg

Once daily for up to 8 weeks

     Short -Term Treatment of Erosive Esophagitis

30 mg

Once daily for up to 8 weeks‡

Pediatric

(1 to 11 years of age)

Short-Term Treatment of Symptomatic GERD and Short-Term Treatment of Erosive Esophagitis

     ≤ 30 kg

15 mg

Once daily for up to 12 weeks§

     > 30 kg

30 mg

Once daily for up to 12 weeks§

(12 to 17 years of age)

Short-Term Treatment of Symptomatic GERD

     Nonerosive GERD

15 mg

Once daily for up to 8 weeks

     Erosive Esophagitis

30 mg

Once daily for up to 8 weeks

Maintenance of Healing of Erosive Esophagitis

15 mg

Once daily

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

60 mg

Once daily¶

Patients should be instructed that if a dose is missed, it should be taken as soon as possible. However, if the next scheduled dose is due, the patient should not take the missed dose and should be instructed to take the next dose on time. Patients should be instructed not to take two doses at one time to make up for a missed dose.

2.2 Special Populations

Renal impairment patients and geriatric patients do not require dosage adjustment. However, consider dose adjustment in patients with severe liver impairment. [See Use in Specific Populations (8.5, 8.6 and 8.7).]

2.3 Important Administration Information

Administration Options

Lansoprazole Delayed-release Capsules -Oral Administration
• Lansoprazole delayed-release capsules should be swallowed whole. • Alternatively, for patients who have difficulty swallowing capsules, lansoprazole delayed-release capsules can be opened and administered as follows: • Open capsule. • Sprinkle intact pellets on one tablespoon of either applesauce, ENSURE ® pudding, cottage cheese, yogurt or strained pears. • Swallow immediately. • Lansoprazole delayed-release capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows: • Open capsule. • Sprinkle intact pellets into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately 2 ounces). • Mix briefly. • Swallow immediately. • To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.
Lansoprazole Delayed-release Capsules -Nasogastric Tube (≥ 16 French) Administration
• For patients who have a nasogastric tube in place, lansoprazole delayed-release capsules can be administered as follows: • Open capsule. • Mix intact pellets into 40 mL of apple juice. DO NOT USE OTHER LIQUIDS. • Inject through the nasogastric tube into the stomach. • Flush with additional apple juice to clear the tube.
USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.
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 of lamotrigine tablets are 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, 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

Drugs other than those listed in the Clinical Pharmacology section [see Clinical Pharmacology (12.3)] have not been systematically evaluated in combination with lamotrigine. 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 and doses of lamotrigine tablets may require adjustment based on clinical response.

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: For women not taking carbamazepine, phenytoin, phenobarbital, primidone or other drugs such as rifampin 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, in order to maintain a consistent lamotrigine plasma level [see Clinical Pharmacology (12.3)].

(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 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 in order 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 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: For women not taking carbamazepine, phenytoin, phenobarbital, primidone or other drugs such as rifampin 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)]. For women taking lamotrigine tablets in addition to carbamazepine, phenytoin, phenobarbital, primidone or other drugs such as rifampin 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 with Hepatic Impairment

Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study in 24 patients 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 reevaluation 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 (5.10)].

Discontinuing carbamazepine, phenytoin, phenobarbital, primidone or other drugs such as rifampin 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, two 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 bipolar patients. 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 (5.10)].

2.2 Epilepsy – Adjunctive Therapy

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

Patients Over 12 Years of Age

Recommended dosing guidelines are summarized in Table 1.
Table 1. Escalation Regimen for Lamotrigine Tablets in Patients Over 12 Years of Age with Epilepsy * Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. † These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect.
For Patients TAKINGValproate*

For Patients NOTTAKINGCarbamazepine,Phenytoin, Phenobarbital,Primidone† orValproate*

For PatientsTAKINGCarbamazepine,Phenytoin,Phenobarbital orPrimidone† andNOTTAKINGValproate*

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 onwardsto maintenance

Increase by 25 to 50 mg/day every 1 to 2 weeks

Increase by 50 mg/day every 1 to 2 weeks

Increase by 100 mg/day every 1 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 2 to 12 Years of Age

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 2 to 12 Years of Age with Epilepsy * Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. † These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect.
For Patients TAKING

Valproate*

For Patients NOTTAKINGCarbamazepine,Phenytoin, Phenobarbital, Primidone† or Valproate*

For Patients TAKINGCarbamazepine,Phenytoin,Phenobarbital orPrimidone† and NOTTAKING Valproate*

Weeks 1 and 2

0.15 mg/kg/day in 1 or 2 divided doses,rounded down to thenearest whole tablet (seeTable 3 for weight baseddosing guide).

0.3 mg/kg/day in 1 or 2 divided doses,rounded down to thenearest whole 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 thenearest whole tablet (see Table 3 for weight based dosing guide).

0.6 mg/kg/day in 2 divided doses,rounded down to thenearest whole tablet.

1.2 mg/kg/day in 2 divided doses,rounded down to thenearest whole tablet.

Week 5onwards to

maintenance

The dose should beincreased every 1 to 2 weeks as follows: calculate 0.3 mg/kg/day, round this amount down to the nearest whole tablet and add thisamount to the previouslyadministered 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 beincreased every 1 to 2 weeks as follows:calculate 1.2 mg/kg/day, round this amountdown to the nearestwhole tablet andadd this amount tothe previouslyadministered dailydose.

Usual

Maintenance

Dose

1 to 5 mg/kg/day (maximum 200 mg/day in 1 or 2 divided doses).1 to 3 mg/kg/day withvalproate alone.

4.5 to 7.5 mg/kg/day (maximum 300 mg/day in 2 divided doses).

5 to 15 mg/kg/day (maximum 400 mg/day in 2 divided 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 increased by as much as 50%, based on clinical response.

May need to beincreased by asmuch as 50%, basedon clinical response.

Note: Only whole tablets should be used for dosing.
Table 3. The Initial Weight-Based Dosing Guide for Patients 2 to 12 Years of Age 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 studies in which the efficacy of lamotrigine 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 through 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 effect the conversion to monotherapy with lamotrigine tablets under conditions that ensure adequate seizure control while mitigating the risk of serious rash associated with the rapid titration of lamotrigine.

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

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].

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 according to the guidelines in Table 1, the concomitant 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 four steps outlined in Table 4.
Table 4. Conversion from Adjunctive Therapy with Valproate to Monotherapy with Lamotrigine Tablets in Patients ≥ 16 Years of Age with Epilepsy
Lamotrigine Tablets

Valproate

Step 1

Achieve a dose of 200 mg/day according toguidelines in Table 1 (if not already on

200 mg/day).

Maintain previous stable dose.

Step 2

Maintain at 200 mg/day.

Decrease to 500 mg/day bydecrements no greater than500 mg/day/week and thenmaintain the dose of 500 mg/day for one week.

Step 3

Increase to 300 mg/day and maintainfor one week.

Simultaneously decrease to250 mg/day and maintain forone week.

Step 4

Increase by 100 mg/day every week to achievemaintenance 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, phenobarbital, phenytoin, 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 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 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 for Patients with Bipolar Disorder * Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. † These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect.
For Patients TAKINGValproate*

For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone† or Valproate*

For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital or Primidone† and NOT TAKING Valproate*

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 for Patients with Bipolar Disorder Following Discontinuation of Psychotropic Medications * These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect. † Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].
Discontinuation of Psychotropic Drugs (excluding Carbamazepine, Phenytoin, Phenobarbital, Primidone* or Valproate†)

After Discontinuation of Valproate†

After Discontinuation of Carbamazepine, Phenytoin, Phenobarbital or Primidone*

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 two 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.
Naproxen

Naproxen

2.1 Instructions for Use in All Patients

Voriconazole tablets should be taken at least one hour before or after a meal.

2.3 Recommended Dosing in Adults

Invasive aspergillosis and serious fungal infections due to Fusarium spp. and Scedosporium apiospermum

See Table 1. Therapy must be initiated with the specified loading dose regimen of intravenous voriconazole on Day 1 followed by the recommended maintenance dose regimen. Intravenous treatment should be continued for at least 7 days. Once the patient has clinically improved and can tolerate medication given by mouth, the oral tablet form or oral suspension form of voriconazole may be utilized. The recommended oral maintenance dose of 200 mg achieves a voriconazole exposure similar to 3 mg/kg IV; a 300 mg oral dose achieves an exposure similar to 4 mg/kg IV. Switching between the intravenous and oral formulations is appropriate because of the high bioavailability of the oral formulation in adults [see Clinical Pharmacology (12)].

Candidemia in nonneutropenic patients and other deep tissue Candida infections

See Table 1. Patients should be treated for at least 14 days following resolution of symptoms or following last positive culture, whichever is longer.

Esophageal Candidiasis

See Table 1. Patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms.
Table 1. Recommended Dosing Regimen * Increase dose when voriconazole is coadministered with phenytoin or efavirenz ( 7); Decrease dose in patients with hepatic impairment ( 2.7). † In healthy volunteer studies, the 200 mg oral q12h dose provided an exposure (AUC τ) similar to a 3 mg/kg IV q12h dose; the 300 mg oral q12h dose provided an exposure (AUC τ) similar to a 4 mg/kg IV q12h dose [ see Clinical Pharmacology (12)]. ‡ Adult patients who weigh less than 40 kg should receive half of the oral maintenance dose. § In a clinical study of invasive aspergillosis, the median duration of IV voriconazole therapy was 10 days (range 2 to 85 days). The median duration of oral voriconazole therapy was 76 days (range 2 to 232 days) [ see Clinical Studies (14.1)]. ¶ In clinical trials, patients with candidemia received 3 mg/kg IV q12h as primary therapy, while patients with other deep tissue Candida infections received 4 mg/kg q12h as salvage therapy. Appropriate dose should be based on the severity and nature of the infection. # Not evaluated in patients with esophageal candidiasis.
Infection

Loading dose

Maintenance Dose*†

IV

IV

Oral‡

Invasive Aspergillosis§

6 mg/kg q12h for the first 24 hours

4 mg/kg q12h

200 mg q12h

Candidemia in non-neutropenic patients and other deep tissue Candida infections

6 mg/kg q12h for the first 24 hours

3 to 4 mg/kg q12h¶

200 mg q12h

Esophageal Candidiasis

#

#

200 mg q12h

Scedosporiosis and

Fusariosis

6 mg/kg q12h for the first 24 hours

4 mg/kg q12h

200 mg q12h

2.4 Dosage Adjustment

If patient response is inadequate, the oral maintenance dose may be increased from 200 mg every 12 hours (similar to 3 mg/kg IV q12h) to 300 mg every 12 hours (similar to 4 mg/kg IV q12h). For adult patients weighing less than 40 kg, the oral maintenance dose may be increased from 100 mg every 12 hours to 150 mg every 12 hours. If patient is unable to tolerate 300 mg orally every 12 hours, reduce the oral maintenance dose by 50 mg steps to a minimum of 200 mg every 12 hours (or to 100 mg every 12 hours for adult patients weighing less than 40 kg).

If patient is unable to tolerate 4 mg/kg IV q12h, reduce the intravenous maintenance dose to 3 mg/kg q12h.

The maintenance dose of voriconazole should be increased when coadministered with phenytoin or efavirenz [see Drug Interactions (7)].

The maintenance dose of voriconazole should be reduced in patients with mild to moderate hepatic impairment, Child-Pugh Class A and B [see Dosage and Administration (2.7)]. There are no PK data to allow for dosage adjustment recommendations in patients with severe hepatic impairment (Child-Pugh Class C).

Duration of therapy should be based on the severity of the patient’s underlying disease, recovery from immunosuppression and clinical response.

2.7 Use in Patients with Hepatic Impairment

In the clinical program, patients were included who had baseline liver function tests (ALT, AST) up to 5 times the upper limit of normal. No dose adjustment is necessary in patients with this degree of abnormal liver function, but continued monitoring of liver function tests for further elevations is recommended [see Warnings and Precautions (5.9)].

It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)].

Voriconazole tablets have not been studied in patients with severe hepatic cirrhosis (Child-Pugh Class C) or in patients with chronic hepatitis B or chronic hepatitis C disease. Voriconazole tablets have been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice and should only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with hepatic insufficiency must be carefully monitored for drug toxicity.

2.8 Use in Patients with Renal Impairment

The pharmacokinetics of orally administered voriconazole tablets are not significantly affected by renal impairment. Therefore, no adjustment is necessary for oral dosing in patients with mild to severe renal impairment [see Clinical Pharmacology (12.3)].

In patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min), accumulation of the intravenous vehicle, SBECD, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the benefit/risk to the patient justifies the use of intravenous voriconazole. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral voriconazole therapy [see Warnings and Precautions (5.10)].

Voriconazole is hemodialyzed with clearance of 121 mL/min. The intravenous vehicle, SBECD, is hemodialyzed with clearance of 55 mL/min. A 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment.
Lithium Carbonate

Lithium Carbonate

Acute Mania

Optimal patient response can usually be established with 1800 mg/day in the following dosages:
* Can also be administered on 600 mg TID recommended dosing interval.
Acute Mania

Morning

Afternoon

Nighttime

Lithium carbonate extended-release tablets*

3 tabs (900 mg)

3 tabs (900 mg)

Such doses will normally produce an effective serum lithium concentration ranging between 1 and 1.5 mEq/L. Dosage must be individualized according to serum concentrations and clinical response. Regular monitoring of the patient’s clinical state and of serum lithium concentrations is necessary. Serum concentrations should be determined twice per week during the acute phase and until the serum concentrations and clinical condition of the patient have been stabilized.

Long-term Control

Desirable serum lithium concentrations are 0.6 to 1.2 mEq/L which can usually be achieved with 900 to 1200 mg/day. Dosage will vary from one individual to another, but generally the following dosages will maintain this concentration:
* Can be administered on TID recommended dosing interval up to 1200 mg/day.
Long-term Control

Morning

Afternoon

Nighttime

Lithium carbonate extended-release tablets*

2 tabs (600 mg)

2 tabs (600 mg)

Serum lithium concentrations in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every 2 months. Patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations of 1 to1.5 mEq/L. Geriatric patients often respond to reduced dosage and may exhibit signs of toxicity at serum concentrations ordinarily tolerated by other patients. In general, dose selection for an elderly patient 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.

Important Considerations
• Blood samples for serum lithium determinations should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8 to 12 hours after previous dose). Total reliance must not be placed on serum concentrations alone. Accurate patient evaluation requires both clinical and laboratory analysis. • Lithium carbonate extended-release tablets must be swallowed whole and never chewed or crushed.
Lithium Carbonate

Lithium Carbonate

Doses of extended-release tablets are usually given b.i.d. (approximately 12-hour intervals). When initiating therapy with extended-release lithium, dosage must be individualized according to serum levels and clinical response.

When switching a patient from immediate-release lithium to lithium carbonate extended-release tablets, give the same total daily dose when possible. Most patients on maintenance therapy are stabilized on 900 mg daily, e.g., lithium carbonate extended-release tablets 450 mg b.i.d. When the previous dosage of immediate-release lithium is not a multiple of 450 mg, e.g., 1,500 mg, initiate lithium carbonate extended-release tablets at the multiple of 450 mg nearest to, but below, the original daily dose, i.e., 1,350 mg. When the two doses are unequal, give the larger dose in the evening. In the above example, with a total daily dose of 1,350 mg, generally 450 mg of lithium carbonate extended-release tablets should be given in the morning and 900 mg of lithium carbonate extended-release tablets in the evening. If desired, the total daily dose of 1,350 mg can be given in three equal 450 mg doses of lithium carbonate extended-release tablets. These patients should be monitored at 1- to 2-week intervals and dosage adjusted if necessary, until stable and satisfactory serum levels and clinical state are achieved.

When patients require closer titration than that available with doses of lithium carbonate extended-release tablets in increments of 450 mg, immediate-release lithium should be used.

Acute Mania

Optimal patient response to lithium carbonate extended-release tablets can usually be established and maintained with 1,800 mg per day in divided doses. Such doses will normally produce the desired serum lithium level ranging between 1 and 1.5 mEq/L.

Dosage must be individualized according to serum levels and clinical response. Regular monitoring of the patient’s clinical state and serum lithium levels is necessary. Serum levels should be determined twice per week during the acute phase and until the serum level and clinical condition of the patient have been stabilized.

Long-Term Control

The desirable serum lithium levels are 0.6 to 1.2 mEq/L. Dosage will vary from one individual to another, but usually 900 mg to 1,200 mg per day in divided doses will maintain this level. Serum lithium levels in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every 2 months.

Patients unusually sensitive to lithium may exhibit toxic signs at serum levels below 1 mEq/L.

N.B.

Blood samples for serum lithium determinations should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8 to 12 hours after the previous dose). Total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and laboratory analysis.

Elderly patients often respond to reduced dosage and may exhibit signs of toxicity at serum levels ordinarily tolerated by younger patients.
Loxapine

Loxapine

Loxapine capsules are administered, usually in divided doses, 2 to 4 times a day. Daily dosage (in terms of base equivalents) should be adjusted to the individual patient's needs as assessed by the severity of symptoms and previous history of response to antipsychotic drugs.

Oral Administration

Initial dosage of 10 mg twice daily is recommended, although in severely disturbed patients initial dosage up to a total of 50 mg daily may be desirable. Dosage should then be increased fairly rapidly over the first 7 to 10 days until there is effective control of symptoms of schizophrenia. The usual therapeutic and maintenance range is 60 mg to 100 mg daily. However, as with other drugs used to treat schizophrenia, some patients respond to lower dosage and others require higher dosage for optimal benefit. Daily dosage higher than 250 mg is not recommended.

Maintenance Therapy

For maintenance therapy, dosage should be reduced to the lowest level compatible with symptom control; many patients have been maintained satisfactorily at dosages in the range of 20 mg to 60 mg daily.
Metformin Hydrochloride...

Metformin Hydrochloride

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with metformin hydrochloride tablets or any other pharmacologic agent. Dosage of metformin hydrochloride 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 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. Metformin hydrochloride 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 tablets and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately 3 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 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 tablets 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 hydrochloride tablets, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

Concomitant Metformin Hydrochloride Tablet and Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to 4 weeks of the maximum dose of metformin hydrochloride tablet monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin hydrochloride 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 tablet 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 500 mg tablets and glyburide 20 mg were titrated to 1000 mg/20 mg, 1500 mg/20 mg, 2000 mg/20 mg or 2500 mg/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 hydrochloride 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 1 to 3 months of concomitant therapy with the maximum dose of metformin hydrochloride tablets and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without metformin hydrochloride tablets.

Concomitant Metformin Hydrochloride Tablet and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of metformin hydrochloride tablet therapy. Metformin hydrochloride tablet therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of metformin hydrochloride tablets should be increased by 500 mg after approximately one 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 hydrochloride tablets. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

Metformin hydrochloride tablets are 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 hydrochloride 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 tablets.

Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly. (See WARNINGS.)
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 tablets 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.
Hydrocortisone

Hydrocortisone

The patient should be placed on a standard cholesterol lowering diet before receiving lovastatin tablets and should continue on this diet during treatment with lovastatin tablets (see NCEP Treatment Guidelines for details on dietary therapy). Lovastatin tablets should be given with meals.

Adult Patients

The usual recommended starting dose is 20 mg once a day given with the evening meal. The recommended dosing range of lovastatin tablets is 10 to 80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day. Doses should be individualized according to the recommended goal of therapy (see NCEP Guidelines and CLINICAL PHARMACOLOGY). Patients requiring reductions in LDL-C of 20% or more to achieve their goal (see INDICATIONS AND USAGE) should be started on 20 mg/day of lovastatin. A starting dose of 10 mg of lovastatin tablets is may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more.

Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of lovastatin tablets if cholesterol levels fall significantly below the targeted range.

Dosage in Patients taking Danazol, Diltiazem, Dronedarone or Verapamil:

In patients taking danazol, diltiazem, dronedarone or verapamil concomitantly with lovastatin tablets, therapy should begin with 10 mg of lovastatin tablets and should not exceed 20 mg/day (see CLINICAL PHARMACOLOGY: Pharmacokinetics, WARNINGS: Myopathy/Rhabdomyolysis, PRECAUTIONS: Drug Interactions: Other Drug Interactions).

Dosage in Patients taking Amiodarone

In patients taking amiodarone concomitantly with lovastatin tablets, the dose should not exceed 40 mg/day (see WARNINGS: Myopathy/Rhabdomyolysis and PRECAUTIONS: Drug Interactions: Other Drug Interactions).

Adolescent Patients (10 to 17 years of age) with Heterozygous Familial Hypercholesterolemia

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 Guidelines3, CLINICAL PHARMACOLOGY and INDICATIONS AND USAGE). Patients requiring reductions in LDL-C of 20% or more to achieve their goal should be started on 20 mg/day of lovastatin tablets. A starting dose of 10 mg of lovastatin tablets may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more.
3 National 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.
Concomitant Lipid-Lowering Therapy

Lovastatin is effective alone or when used concomitantly with bile-acid sequestrants (see WARNINGS: Myopathy/Rhabdomyolysis and PRECAUTIONS: Drug Interactions).

Dosage in Patients with Renal Insufficiency

In patients with severe renal insufficiency (creatinine clearance < 30 mL/min), dosage increases above 20 mg/day should be carefully considered and, if deemed necessary, implemented cautiously (see CLINICAL PHARMACOLOGY and WARNINGS: Myopathy/Rhabdomyolysis).
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 Partial Onset Seizures

Adults 16 Years and Older

In clinical trials, daily doses of 1000 mg, 2000 mg and 3000 mg, given as twice daily dosing were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose [see Clinical Studies (14.1)], a consistent increase in response with increased dose has not been shown.

Treatment should be initiated 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. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients

Dosing information in pediatric patients less than 4 years of age as adjunctive therapy in the treatment of partial onset seizures is approved for UCB, Inc.’s levetiracetam tablets and oral solution. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

4 Years to < 16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in two divided doses (10 mg/kg twice daily). The daily dose should be increased 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 efficacy 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 kg to 40 kg, treatment should be initiated with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). The daily dose should be increased 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, treatment should be initiated with a daily dose of 1000 mg/day given as twice daily dosing (500 mg twice daily). The daily dose should be increased 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:

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

Treatment should be initiated with a dose of 1000 mg/day, given as twice daily dosing (500 mg twice daily). Dosage should be increased 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 Primary Generalized Tonic-Clonic Seizures

Adults 16 Years and Older

Treatment should be initiated with a dose of 1000 mg/day, given as twice daily dosing (500 mg twice daily). Dosage should be increased 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 Years

Treatment should be initiated with a daily dose of 20 mg/kg in two divided doses (10 mg/kg twice daily). The daily dose should be increased 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 Adult Patients with Impaired Renal Function

Levetiracetam tablet dosing must be individualized according to the patient’s renal function status. Recommended doses and adjustment for dose 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:

Then CLcr is adjusted for body surface area (BSA) as follows:

Table 1: Dosing Adjustment Regimen for Adult Patients with Impaired Renal Function * Following dialysis, a 250 mg to 500 mg supplemental dose is recommended.
Group

Creatinine Clearance(mL/min/1.73m2)

Dosage (mg)

Frequency

Normal

> 80

500 to 1500

Every 12 hours

Mild

50 to 80

500 to 1000

Every 12 hours

Moderate

30 to 50

250 to 750

Every 12 hours

Severe

< 30

250 to 500

Every 12 hours

ESRD patients using dialysis

---

500 to 1000*

Every 24 hours*
Sulfamylon

Sulfamylon

SULFAMYLON® For 5% Topical Solution

Directions for Preparation of the Solution

SULFAMYLON® (mafenide acetate) For 5% Topical Solution is supplied as a sterile powder and is to be reconstituted with Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. Aseptic techniques should be observed during preparation of the solution. Premeasured quantities of 50 g of mafenide acetate powder are provided in sterile packets. The entire quantity of SULFAMYLON® should be emptied into a suitable container which contains 1000 mL of Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP and mixed until completely dissolved. The reconstituted solution may be held up to 28 days after preparation if stored in unopened containers. ONCE A CONTAINER IS OPENED, ANY UNUSED PORTION SHOULD BE DISCARDED AFTER 48 HOURS. Store the reconstituted solution at 20° to 25°C (68° to 77°F). Limited storage periods at 15° to 30°C (59° to 86°F) are acceptable. Not for Injection - For Topical Use Only.

Directions for Use of the Solution

The grafted area should be covered with one layer of fine mesh gauze. An eight-ply burn dressing should be cut to the size of the graft and wetted with SULFAMYLON® (mafenide acetate, USP) For 5% Topical Solution using an irrigation syringe and/or irrigation tubing until leaking is noticeable. If irrigation tubing is used, the tubing should be placed over the burn dressing in contact with the wound and covered with a second piece of eight-ply dressing. The irrigation dressing should be secured with a bolster dressing and wrapped as appropriate. The gauze dressing should be kept wet. In clinical studies, this has been accomplished by irrigating with a syringe or injecting the solution into the irrigation tubing every 4 hours or as necessary. If irrigation tubing is not used, the gauze dressing may be moistened every 6-8 hours or as necessary to keep wet.

Wound dressings may be left undisturbed, except for the irrigations, for up to five days. Additional soaks may be initiated until graft take is complete. Maceration of skin may result from wet dressings applied for intervals as short as 24 hours. Treatment is usually continued until autograft vascularization occurs and healing is progressing (typically occurring in about 5 days). Safety and effectiveness have not been established for longer than 5 days for an individual grafting procedure.

If allergic manifestations occur during treatment with SULFAMYLON® (mafenide acetate, USP) For 5% Topical Solution, discontinuation of treatment should be considered. If acidosis occurs and becomes difficult to control, particularly in patients with pulmonary dysfunction, discontinuing the soaks with the mafenide acetate solution for 24 to 48 hours may aid in restoring acid-base balance (see PRECAUTIONS section). Dressing changes and monitoring the site for bacterial growth during this interruption should be adjusted accordingly.
Lorazepam

Lorazepam

Lorazepam tablets are administered orally. For optimal results, dose, frequency of administration, and duration of therapy should be individualized according to patient response. To facilitate this, 0.5 mg, 1 mg, and 2 mg tablets are available.

The usual range is 2 to 6 mg/day given in divided doses, the largest dose being taken before bedtime, but the daily dosage may vary from 1 to 10 mg/day.

For anxiety, most patients require an initial dose of 2 to 3 mg/day given b.i.d. or t.i.d.

For insomnia due to anxiety or transient situational stress, a single daily dose of 2 mg to 4 mg may be given, usually at bedtime.

For elderly or debilitated patients, an initial dosage of 1 to 2 mg/day in divided doses is recommended, to be adjusted as needed and tolerated.

The dosage of lorazepam tablets should be increased gradually when needed to help avoid adverse effects. When higher dosage is indicated, the evening dose should be increased before the daytime doses.
Calphron

Calphron

Nitrofurantoin monohydrate/macrocrystals capsules should be taken with food.

Adults and Pediatric Patients Over 12 Years: One 100 mg capsule every 12 hours for 7 days.
Tussin Cf Nighttime Cou...

Tussin Cf Nighttime Cough And Cold

Apply sufficient quantity to adequately cover all lesions every 3 hours, 6 times per day for 7 days. The dose size per application will vary depending upon the total lesion area but should approximate a one-half inch ribbon of ointment per 4 square inches of surface area. A finger cot or rubber glove should be used when applying acyclovir ointment to prevent autoinoculation of other body sites and transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms.
Omnicide Antimicrobial

Omnicide Antimicrobial

The dose of propafenone HCl must be individually titrated on the basis of response and tolerance. It is recommended that therapy be initiated with 150 mg propafenone given every eight hours (450 mg/day). Dosage may be increased at a minimum of 3 to 4 day intervals to 225 mg every 8 hours (675 mg/day) and, if necessary, to 300 mg every 8 hours (900 mg/day). The usefulness and safety of dosages exceeding 900 mg per day have not been established. In those patients in whom significant widening of the QRS complex or second or third degree AV block occurs, dose reduction should be considered.

As with other antiarrhythmic agents, in the elderly or in ventricular arrhythmia patients with marked previous myocardial damage, the dose of propafenone HCl should be increased more gradually during the initial phase of treatment.
Levothyroxine Sodium

Levothyroxine Sodium

General Principles

The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of levothyroxine sodium tablets that is adequate to achieve these goals depends on a variety of factors including the patient’s age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated (see WARNINGS and PRECAUTIONS). Hence, the following recommendations serve only as dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient’s clinical response and laboratory parameters (see PRECAUTIONS: Laboratory Tests).

Levothyroxine sodium tablets should be taken in the morning on an empty stomach, at least one-half hour before any food is eaten. Levothyroxine sodium tablets should be taken at least 4 hours apart from drugs that are known to interfere with its absorption (see PRECAUTIONS: Drug Interactions).

Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not be attained for 4 to 6 weeks.

Caution should be exercised when administering levothyroxine sodium tablets to patients with underlying cardiovascular disease, to the elderly, and to those with concomitant adrenal insufficiency (see PRECAUTIONS).

Specific Patient Populations

Hypothyroidism in Adults and in Children in Whom Growth and Puberty are Complete

(see WARNINGS and PRECAUTIONS: Laboratory Tests)

Therapy may begin at full replacement doses in otherwise healthy individuals less than 50 years old and in those older than 50 years who have been recently treated for hyperthyroidism or who have been hypothyroid for only a short time (such as a few months). The average full replacement dose of levothyroxine sodium is approximately 1.7 mcg/kg/day (e.g., 100 to 125 mcg/day for a 70 kg adult). Older patients may require less than 1 mcg/kg/day. Levothyroxine sodium doses greater than 200 mcg/day are seldom required. An inadequate response to daily doses ≥ 300 mcg/day is rare and may indicate poor compliance, malabsorption, and/or drug interactions.

For most patients older than 50 years or for patients under 50 years of age with underlying cardiac disease, an initial starting dose of 25 to 50 mcg/day of levothyroxine sodium is recommended, with gradual increments in dose at 6 to 8 week intervals, as needed. The recommended starting dose of levothyroxine sodium in elderly patients with cardiac disease is 12.5 to 25 mcg/day, with gradual dose increments at 4 to 6 week intervals. The levothyroxine sodium dose is generally adjusted in 12.5 mcg to 25 mcg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized.

In patients with severe hypothyroidism, the recommended initial levothyroxine sodium dose is 12.5 to 25 mcg/day with increases of 25 mcg/day every 2 to 4 weeks, accompanied by clinical and laboratory assessment, until the TSH level is normalized.

In patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism, the levothyroxine sodium dose should be titrated until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range.

Pediatric Dosage - Congenital or Acquired Hypothyroidism

(see PRECAUTIONS: Laboratory Tests)

General Principles

In general, levothyroxine therapy should be instituted at full replacement doses as soon as possible. Delays in diagnosis and institution of therapy may have deleterious effects on the child’s intellectual and physical growth and development.

Undertreatment and overtreatment should be avoided (see PRECAUTIONS: Pediatric Use).

Levothyroxine sodium tablets may be administered to infants and children who cannot swallow intact tablets by crushing the tablet and suspending the freshly crushed tablet in a small amount (5 to 10 mL or 1 to 2 teaspoons) of water. This suspension can be administered by spoon or by dropper. DO NOT STORE THE SUSPENSION. Foods that decrease absorption of levothyroxine, such as soybean infant formula, should not be used for administering levothyroxine sodium tablets (see PRECAUTIONS: Drug-Food Interactions).

Newborns

The recommended starting dose of levothyroxine sodium in newborn infants is 10 to 15 mcg/kg/day. A lower starting dose (e.g., 25 mcg/day) should be considered in infants at risk for cardiac failure, and the dose should be increased in 4 to 6 weeks as needed based on clinical and laboratory response to treatment. In infants with very low (< 5 mcg/dL) or undetectable serum T4 concentrations, the recommended initial starting dose is 50 mcg/day of levothyroxine sodium.

Infants and Children

Levothyroxine therapy is usually initiated at full replacement doses, with the recommended dose per body weight decreasing with age (see Table 3). However, in children with chronic or severe hypothyroidism, an initial dose of 25 mcg/day of levothyroxine sodium is recommended with increments of 25 mcg every 2 to 4 weeks until the desired effect is achieved.

Hyperactivity in an older child can be minimized if the starting dose is one-fourth of the recommended full replacement dose, and the dose is then increased on a weekly basis by an amount equal to one-fourth the full recommended replacement dose until the full recommended replacement dose is reached.
Table 3: Levothyroxine Sodium Dosing Guidelines for Pediatric Hypothyroidism * The dose should be adjusted based on clinical response and laboratory parameters (see PRECAUTIONS: Laboratory Tests and PRECAUTIONS: Pediatric Use).
AGE

Daily Dose Per Kg Body Weight*

0 to 3 months

10 to 15 mcg/kg/day

3 to 6 months

8 to 10 mcg/kg/day

6 to 12 months

6 to 8 mcg/kg/day

1 to 5 years

5 to 6 mcg/kg/day

6 to 12 years

4 to 5 mcg/kg/day

> 12 years but growth and puberty incomplete

2 to 3 mcg/kg/day

Growth and puberty complete

1.7 mcg/kg/day

Pregnancy

Pregnancy may increase levothyroxine requirements (see PRECAUTIONS: Pregnancy).

Subclinical Hypothyroidism

If this condition is treated, a lower levothyroxine sodium dose (e.g., 1 mcg/kg/day) than that used for full replacement may be adequate to normalize the serum TSH level. Patients who are not treated should be monitored yearly for changes in clinical status and thyroid laboratory parameters.

TSH Suppression in Well Differentiated Thyroid Cancer and Thyroid Nodules

The target level for TSH suppression in these conditions has not been established with controlled studies. In addition, the efficacy of TSH suppression for benign nodular disease is controversial. Therefore, the dose of levothyroxine sodium tablets used for TSH suppression should be individualized based on the specific disease and the patient being treated.

In the treatment of well differentiated (papillary and follicular) thyroid cancer, levothyroxine is used as an adjunct to surgery and radioiodine therapy. Generally, TSH is suppressed to < 0.1 mU/L, and this usually requires a levothyroxine sodium dose of greater than 2 mcg/kg/day. However, in patients with high risk tumors, the target level for TSH suppression may be < 0.01 mU/L.

In the treatment of benign nodules and nontoxic multinodular goiter, TSH is generally suppressed to a higher target (e.g., 0.1 to 0.5 mU/L for nodules and 0.5 to 1.0 mU/L for multinodular goiter) than that used for the treatment of thyroid cancer. Levothyroxine sodium is contraindicated if the serum TSH is already suppressed due to the risk of precipitating overt thyrotoxicosis (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS).

Myxedema Coma

Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, and may result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract. Therefore, oral thyroid hormone drug products are not recommended to treat this condition. Thyroid hormone products formulated for intravenous administration should be administered.
Atorvastatin Calcium

Atorvastatin Calcium

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 tablet 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 one 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 Total Daily Dose (mg)

Divalproex Sodium Extended-release Tablets (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.
Granulex

Granulex

There is currently no dosage information available for this product. We apologize for any inconvenience.
Ondansetron Hydrochlori...

Ondansetron Hydrochloride

Adults

Initiation of Therapy

The usual starting dosage of methyldopa tablet is 250 mg two to three times a day in the first 48 hours. The daily dosage then may be increased or decreased, preferably at intervals of not less than two days, until an adequate response is achieved. To minimize the sedation, start dosage increases in the evening. By adjustment of dosage, morning hypotension may be prevented without sacrificing control of afternoon blood pressure.

When methyldopa is given to patients on other antihypertensives, the dose of these agents may need to be adjusted to effect a smooth transition. When methyldopa is given with anti-hypertensives other than thiazides, the initial dosage of methyldopa should be limited to 500 mg daily in divided doses; when methyldopa is added to a thiazide, the dosage of thiazide need not be changed.

Maintenance of Therapy

The usual daily dosage of methyldopa is 500 mg to 2 g in two to four doses. Although occasional patients have responded to higher doses, the maximum recommended daily dosage is 3 g. Once an effective dosage range is attained, a smooth blood pressure response occurs in most patients in 12 to 24 hours. Since methyldopa has a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours. This is not complicated by an overshoot of blood pressure.

Occasionally tolerance may occur, usually between the second and third month of therapy. Adding a diuretic or increasing the dosage of methyldopa frequently will restore effective control of blood pressure. A thiazide may be added at any time during methyldopa therapy and is recommended if therapy has not been started with a thiazide or if effective control of blood pressure cannot be maintained on 2 g of methyldopa daily.

Methyldopa is largely excreted by the kidney and patients with impaired renal function may respond to smaller doses. Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses.

Pediatric Patients

Initial dosage is based on 10 mg/kg of body weight daily in two to four doses. The daily dosage then is increased or decreased until an adequate response is achieved. The maximum dosage is 65 mg/kg or 3 g daily, whichever is less. (See PRECAUTIONS: Pediatric Use.)
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 4 to 6 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.
Capecitabine

Capecitabine

Capecitabine tablets should be swallowed whole with water within 30 minutes after a meal. Capecitabine dose is calculated according to body surface area.

2.1 Standard Starting Dose

Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer)

The recommended dose of capecitabine is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1 week rest period given as 3 week cycles (see Table 1).

Adjuvant treatment in patients with Dukes’ C colon cancer is recommended for a total of 6 months [i.e., capecitabine 1250 mg/m2 orally twice daily for 2 weeks followed by a 1 week rest period, given as 3 week cycles for a total of 8 cycles (24 weeks)].
Table 1. Capecitabine Dose Calculation According to Body Surface Area * Total Daily Dose divided by two to allow equal morning and evening doses
Dose Level 1250 mg/m2

Twice a Day

Number of Tablets to be Taken at

Each Dose (Morning and Evening)

Surface Area

(m2)

Total Daily Dose* (mg)

150 mg

500 mg

≤1.25

3000

0

3

1.26 to 1.37

3300

1

3

1.38 to 1.51

3600

2

3

1.52 to 1.65

4000

0

4

1.66 to 1.77

4300

1

4

1.78 to 1.91

4600

2

4

1.92 to 2.05

5000

0

5

2.06 to 2.17

5300

1

5

≥ 2.18

5600

2

5

In Combination With Docetaxel (Metastatic Breast Cancer)

In combination with docetaxel, the recommended dose of capecitabine is 1250 mg/m2 twice daily for 2 weeks followed by a 1 week rest period, combined with docetaxel at 75 mg/m2 as a 1 hour intravenous infusion every 3 weeks. Pre-medication, according to the docetaxel labeling, should be started prior to docetaxel administration for patients receiving the capecitabine tablets plus docetaxel combination. Table 1 displays the total daily dose of capecitabine by body surface area and the number of tablets to be taken at each dose.

2.2 Dose Management Guidelines

General

Capecitabine dosage may need to be individualized to optimize patient management. Patients should be carefully monitored for toxicity and doses of capecitabine should be modified as necessary to accommodate individual patient tolerance to treatment [see Clinical Studies (14)]. Toxicity due to capecitabine tablet administration may be managed by symptomatic treatment, dose interruptions and adjustment of capecitabine dose. Once the dose has been reduced, it should not be increased at a later time. Doses of capecitabine omitted for toxicity are not replaced or restored; instead the patient should resume the planned treatment cycles.

The dose of phenytoin and the dose of coumarin-derivative anticoagulants may need to be reduced when either drug is administered concomitantly with capecitabine tablets [see Drug Interactions (7.1)].

Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer)

Capecitabine dose modification scheme as described below (see Table 2) is recommended for the management of adverse reactions.
Table 2. Recommended Dose Modifications of Capecitabine * National Cancer Institute of Canada Common Toxicity Criteria were used except for the hand-and-foot syndrome [see Warnings and Precautions (5)].
Toxicity

NCIC Grades*

During a Course of Therapy

Dose Adjustment for Next

Treatment (% of starting dose)

Grade 1

Maintain dose level

Maintain dose level

Grade 2

-1st appearance

Interrupt until resolved to grade 0-1

100%

-2nd appearance

75%

-3rd appearance

50%

-4th appearance

Discontinue treatment permanently

-

Grade 3

-1st appearance

Interrupt until resolved to grade 0-1

75%

-2nd appearance

50%

-3rd appearance

Discontinue treatment permanently

-

Grade 4

-1st appearance

Discontinue permanently

OR

If physician deems it to be in the

patient’s best interest to continue,

interrupt until resolved to grade 0-1

50%

In Combination with Docetaxel (Metastatic Breast Cancer)

Dose modifications of capecitabine tablets for toxicity should be made according to Table 2 above for capecitabine. At the beginning of a treatment cycle, if a treatment delay is indicated for either capecitabine or docetaxel, then administration of both agents should be delayed until the requirements for restarting both drugs are met.

The dose reduction schedule for docetaxel when used in combination with capecitabine for the treatment of metastatic breast cancer is shown in Table 3.
Table 3. Docetaxel Dose Reduction Schedule in Combination with Capecitabine * National Cancer Institute of Canada Common Toxicity Criteria were used except for hand-and-foot syndrome [see Warnings and Precautions (5)].
Toxicity NCIC Grades*

Grade 2

Grade 3

Grade 4

1st appearance

Delay treatment until resolved to grade 0-1; Resume treatment with original dose of 75 mg/m2 docetaxel

Delay treatment until resolved to grade 0-1; Resume treatment at 55 mg/m2 of docetaxel

Discontinue treatment with docetaxel

2nd appearance

Delay treatment until resolved to grade 0-1; Resume treatment at 55 mg/m2 of docetaxel

Discontinue treatment with docetaxel

-

3rd appearance

Discontinue treatment with docetaxel

-

-

2.3 Adjustment of Starting Dose in Special Populations

Renal Impairment

No adjustment to the starting dose of capecitabine is recommended in patients with mild renal impairment (creatinine clearance = 51 to 80 mL/min [Cockroft and Gault, as shown below]). In patients with moderate renal impairment (baseline creatinine clearance = 30 to 50 mL/min), a dose reduction to 75% of the capecitabine starting dose when used as monotherapy or in combination with docetaxel (from 1250 mg/m2 to 950 mg/m2 twice daily) is recommended [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Subsequent dose adjustment is recommended as outlined in Table 2 and Table 3 (depending on the regimen) if a patient develops a grade 2 to 4 adverse event [see Warnings and Precautions (5.5)]. The starting dose adjustment recommendations for patients with moderate renal impairment apply to both capecitabine monotherapy and capecitabine in combination use with docetaxel.

Cockroft and Gault Equation:

Creatinine clearance for males =

(140 –age [yrs]) (body wt [kg])

(72) (serum creatinine [mg/dL])

Creatinine clearance for females = 0.85 x male value

Geriatrics

Physicians should exercise caution in monitoring the effects of capecitabine tablets in the elderly. Insufficient data are available to provide a dosage recommendation.
Ondansetron Hydrochlori...

Ondansetron Hydrochloride

adults and children6 years and over

1 tablet daily; not morethan 1 tablet in 24 hours

children under 6 years of age

ask a doctor

consumers with liveror kidney disease

ask a doctor
Entecavir

Entecavir

Nitrofurantoin macrocrystals capsules should be given with food to improve drug absorption and, in some patients, tolerance.

Adults: 50 mg to 100 mg four times a day – the lower dosage level is recommended for uncomplicated urinary tract infections.

Pediatric Patients: 5 to 7 mg/kg of body weight per 24 hours, given in four divided doses (contraindicated under one month of age).

Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. Continued infection indicates the need for reevaluation.

For long-term suppressive therapy in adults, a reduction of dosage to 50 mg to 100 mg at bedtime may be adequate. For long-term suppressive therapy in pediatric patients, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate. SEE WARNINGS SECTION REGARDING RISKS ASSOCIATED WITH LONG-TERM THERAPY.
Enalapril Maleate

Enalapril Maleate

Hypertension

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may occur following the initial dose of enalapril maleate tablets. The diuretic should, if possible, be discontinued for 2 to 3 days before beginning therapy with enalapril maleate tablets to reduce the likelihood of hypotension. (See WARNINGS.) If the patient's blood pressure is not controlled with enalapril maleate tablets alone, diuretic therapy may be resumed.

If the diuretic cannot be discontinued an initial dose of 2.5 mg should be used under medical supervision for at least 2 hours and until blood pressure has stabilized for at least an additional hour. (See WARNINGS and PRECAUTIONS: Drug Interactions.)

The recommended initial dose in patients not on diuretics is 5 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 10 mg to 40 mg per day administered in a single dose or two 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 should be considered. If blood pressure is not controlled with enalapril maleate tablets alone, a diuretic may be added.

Concomitant administration of enalapril maleate tablets with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics may lead to increases of serum potassium (see PRECAUTIONS).

Dosage Adjustment in Hypertensive Patients with Renal Impairment

The usual dose of enalapril maleate tablets is recommended for patients with a creatinine clearance > 30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance ≤ 30 mL/min (serum creatinine ≥ 3 mg/dL), the first dose is 2.5 mg once daily. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.
* See WARNINGS: Anaphylactoid Reactions During Membrane Exposure. † Dosage on nondialysis days should be adjusted depending on the blood pressure response.
Renal Status

Creatinine-Clearance mL/min

Initial Dose mg/day

Normal Renal Function

> 80 mL/min

5 mg

Mild Impairment

≤ 80 > 30 mL/min

5 mg

Moderate to Severe Impairment

≤ 30 mL/min

2.5 mg

Dialysis Patients*

—

2.5 mg on dialysis days†

Heart Failure

Enalapril maleate tablets are indicated for the treatment of symptomatic heart failure, usually in combination with diuretics and digitalis. In the placebo-controlled studies that demonstrated improved survival, patients were titrated as tolerated up to 40 mg, administered in two divided doses.

The recommended initial dose is 2.5 mg. The recommended dosing range is 2.5 mg to 20 mg given twice a day. Doses should be titrated upward, as tolerated, over a period of a few days or weeks. The maximum daily dose administered in clinical trials was 40 mg in divided doses.

After the initial dose of enalapril maleate tablets, the patient should be observed under medical supervision for at least 2 hours and until blood pressure has stabilized for at least an additional hour. (See WARNINGS and PRECAUTIONS: Drug Interactions.) If possible, the dose of any concomitant diuretic should be reduced which may diminish the likelihood of hypotension. The appearance of hypotension after the initial dose of enalapril maleate tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

Asymptomatic Left Ventricular Dysfunction

In the trial that demonstrated efficacy, patients were started on 2.5 mg twice daily and were titrated as tolerated to the targeted daily dose of 20 mg (in divided doses).

After the initial dose of enalapril maleate tablets, the patient should be observed under medical supervision for at least 2 hours and until blood pressure has stabilized for at least an additional hour. (See WARNINGS and PRECAUTIONS: Drug Interactions.) If possible, the dose of any concomitant diuretic should be reduced which may diminish the likelihood of hypotension. The appearance of hypotension after the initial dose of enalapril maleate tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

Dosage Adjustment in Patients with Heart Failure and Renal Impairment or Hyponatremia

In patients with heart failure who have hyponatremia (serum sodium less than 130 mEq/L) or with serum creatinine greater than 1.6 mg/dL, therapy should be initiated at 2.5 mg daily under close medical supervision. (See DOSAGE AND ADMINISTRATION: Heart Failure, WARNINGS and PRECAUTIONS: Drug Interactions.) The dose may be increased to 2.5 mg b.i.d., then 5 mg b.i.d. and higher as needed, usually at intervals of 4 days or more if at the time of dosage adjustment there is not excessive hypotension or significant deterioration of renal function. The maximum daily dose is 40 mg.

Pediatric Hypertensive Patients

The usual recommended starting dose is 0.08 mg/kg (up to 5 mg) once daily. Dosage should be adjusted according to blood pressure response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients (see CLINICAL PHARMACOLOGY: Clinical Pharmacology in Pediatric Patients).

Enalapril maleate tablets are not recommended in neonates and in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2, as no data are available.

Preparation of Suspension (for 200 mL of a 1 mg/mL suspension)

Add 50 mL of Bicitra®1 to a polyethylene terephthalate (PET) bottle containing ten 20 mg tablets of enalapril maleate and shake for at least 2 minutes. Let concentrate stand for 60 minutes. Following the 60 minute hold time, shake the concentrate for an additional minute. Add 150 mL of Ora-Sweet SF™2 to the concentrate in the PET 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. Shake the suspension before each use.
1 Registered trademark of Alza Corporation 2 Trademark of Paddock Laboratories, Inc.
Acnefree Clear Skin Tre...

Acnefree Clear Skin Treatments 24 Hour Severe Acne Clearing System

BECAUSE OF THE UNIQUE PHARMACOKINETIC PROPERTIES, DIFFICULT DOSING SCHEDULE, AND SEVERITY OF THE SIDE EFFECTS IF PATIENTS ARE IMPROPERLY MONITORED, AMIODARONE HYDROCHLORIDE TABLETS SHOULD BE ADMINISTERED ONLY BY PHYSICIANS WHO ARE EXPERIENCED IN THE TREATMENT OF LIFE-THREATENING ARRHYTHMIAS WHO ARE THOROUGHLY FAMILIAR WITH THE RISKS AND BENEFITS OF AMIODARONE THERAPY, AND WHO HAVE ACCESS TO LABORATORY FACILITIES CAPABLE OF ADEQUATELY MONITORING THE EFFECTIVENESS AND SIDE EFFECTS OF TREATMENT.

In order to insure that an antiarrhythmic effect will be observed without waiting several months, loading doses are required. A uniform, optimal dosage schedule for administration of amiodarone hydrochloride tablets has not been determined. Because of the food effect on absorption, amiodarone hydrochloride tablets should be administered consistently with regard to meals (see CLINICAL PHARMACOLOGY). Individual patient titration is suggested according to the following guidelines:

For Life-Threatening Ventricular Arrhythmias, Such as Ventricular Fibrillation or Hemodynamically Unstable Ventricular Tachycardia

Close monitoring of the patients is indicated during the loading phase, particularly until risk of recurrent ventricular tachycardia or fibrillation has abated. Because of the serious nature of the arrhythmia and the lack of predictable time course of effect, loading should be performed in a hospital setting. Loading doses of 800 to 1,600 mg/day are required for 1 to 3 weeks (occasionally longer) until initial therapeutic response occurs. (Administration of amiodarone hydrochloride tablets in divided doses with meals is suggested for total daily doses of 1,000 mg or higher, or when gastrointestinal intolerance occurs.) If side effects become excessive, the dose should be reduced. Elimination of recurrence of ventricular fibrillation and tachycardia usually occurs within 1 to 3 weeks, along with reduction in complex and total ventricular ectopic beats.

Since grapefruit juice is known to inhibit CYP3A4-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, grapefruit juice should not be taken during treatment with oral amiodarone (see PRECAUTIONS, Drug Interactions).

Upon starting amiodarone hydrochloride tablet therapy, an attempt should be made to gradually discontinue prior antiarrhythmic drugs (see PRECAUTIONS, Drug Interactions). When adequate arrhythmia control is achieved, or if side effects become prominent, amiodarone hydrochloride tablet dose should be reduced to 600 to 800 mg/day for one month and then to the maintenance dose, usually 400 mg/day (see CLINICAL PHARMACOLOGY, Monitoring Effectiveness). Some patients may require larger maintenance doses, up to 600 mg/day, and some can be controlled on lower doses. Amiodarone hydrochloride tablets may be administered as a single daily dose, or in patients with severe gastrointestinal intolerance, as a b.i.d. dose. In each patient, the chronic maintenance dose should be determined according to antiarrhythmic effect as assessed by symptoms, Holter recordings, and/or programmed electrical stimulation and by patient tolerance. Plasma concentrations may be helpful in evaluating nonresponsiveness or unexpectedly severe toxicity (see CLINICAL PHARMACOLOGY).

The lowest effective dose should be used to prevent the occurrence of side effects. In all instances, the physician must be guided by the severity of the individual patient’s arrhythmia and response to therapy.

When dosage adjustments are necessary, the patient should be closely monitored for an extended period of time because of the long and variable half-life of amiodarone and the difficulty in predicting the time required to attain a new steady-state level of drug. Dosage suggestions are summarized below:

Loading Dose

Adjustment and Maintenance Dose

(Daily)

(Daily)

Ventricular Arrhythmias

1 to 3 weeks

~1 month

usual maintenance

800 to 1,600 mg

600 to 800 mg

400 mg
Sinus Pressure And Pain...

Sinus Pressure And Pain Maximum Strength

The following dosages of albuterol tablets are expressed in terms of albuterol base.

Usual Dosage

Adults and Children Over 12 Years of Age

The usual starting dosage for adults and children 12 years and older is 2 or 4 mg three or four times a day.

Children 6 to 12 Years of Age

The usual starting dosage for children 6 to 12 years of age is 2 mg three or four times a day.

Dosage Adjustment

Adults and Children Over 12 Years of Age

For adults and children 12 years and older, a dosage above 4 mg four times a day should be used only when the patient fails to respond. If a favorable response does not occur with the 4 mg initial dosage, it should be cautiously increased stepwise up to a maximum of 8 mg four times a day as tolerated.

Children 6 to 12 Years of Age Who Fail to Respond to the Initial Starting Dosage of 2 mg Four Times a Day

For children from 6 to 12 years of age who fail to respond to the initial starting dosage of 2 mg four times a day, the dosage may be cautiously increased stepwise, but not to exceed 24 mg/day (given in divided doses).

Elderly Patients and Those Sensitive to Beta-adrenergic Stimulators

An initial dosage of 2 mg three or four times a day is recommended for elderly patients and for those with a history of unusual sensitivity to beta-adrenergic stimulators. If adequate bronchodilation is not obtained, dosage may be increased gradually to as much as 8 mg three or four times a day.

The total daily dose should not exceed 32 mg in adults and children 12 years and older.
Glycopyrrolate

Glycopyrrolate

The dosage of glycopyrrolate tablets 1 mg or 2 mg should be adjusted to the needs of the individual patient to assure symptomatic control with a minimum of adverse reactions. The presently recommended maximum daily dosage of glycopyrrolate is 8 mg.

Glycopyrrolate tablets 1 mg.

The recommended initial dosage of glycopyrrolate tablets 1 mg for adults is one tablet three times daily (in the morning, early afternoon, and at bedtime). Some patients may require two tablets at bedtime to assure overnight control of symptoms. For maintenance, a dosage of one tablet twice a day is frequently adequate.

Glycopyrrolate tablets 2 mg.

The recommended dosage of glycopyrrolate tablets 2 mg for adults is one tablet two or three times daily at equally spaced intervals.

Glycopyrrolate tablets are not recommended for use in pediatric patients under the age of 12 years.
Hydroxyzine Pamoate

Hydroxyzine Pamoate

For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested: in adults, 50 to 100 mg q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 to 100 mg daily in divided doses.

For use in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus: in adults, 25 mg t.i.d. or q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 to 100 mg daily in divided doses.

As a sedative when used as a premedication and following general anesthesia: 50 to 100 mg in adults, and 0.6 mg/kg in children.

When treatment is initiated by the intramuscular route of administration, subsequent doses may be administered orally.

As with all medications, the dosage should be adjusted according to the patient’s response to therapy.
Indapamide

Indapamide

Hypertension

The adult starting indapamide dose for hypertension is 1.25 mg as a single daily dose taken in the morning. If the response to 1.25 mg is not satisfactory after 4 weeks, the daily dose may be increased to 2.5 mg taken once daily. If the response to 2.5 mg is not satisfactory after 4 weeks, the daily dose may be increased to 5 mg taken once daily, but adding another antihypertensive should be considered.

Edema of Congestive Heart Failure

The adult starting indapamide dose for edema of congestive heart failure is 2.5 mg as a single daily dose taken in the morning. If the response to 2.5 mg is not satisfactory after one week, the daily dose may be increased to 5 mg taken once daily.

If the antihypertensive response to indapamide is insufficient, indapamide may be combined with other antihypertensive drugs, with careful monitoring of blood pressure. It is recommended that the usual dose of other agents be reduced by 50% during initial combination therapy. As the blood pressure response becomes evident, further dosage adjustments may be necessary.

In general, doses of 5 mg and larger have not appeared to provide additional effects on blood pressure or heart failure, but are associated with a greater degree of hypokalemia. There is minimal clinical trial experience in patients with doses greater than 5 mg once a day.
Glyburide

Glyburide

Patients should be retitrated when transferred from glyburide (micronized) tablets or other oral hypoglycemic agents (see PRECAUTIONS).

There is no fixed dosage regimen for the management of diabetes mellitus with glyburide tablets or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient’s blood glucose must also 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 adequate blood glucose lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient’s response to therapy.

Short-term administration of glyburide tablets may be sufficient during periods of transient loss of control in patients usually controlled well on diet.

Usual Starting Dose

The usual starting dose of glyburide tablets is 2.5 to 5 mg daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1.25 mg daily. (See PRECAUTIONS section for patients at increased risk.) Failure to follow an appropriate dosage regimen may precipitate hypoglycemia. Patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy.

Transfer From Other Hypoglycemic Therapy Patients Receiving Other Oral Antidiabetic Therapy

Transfer of patients from other oral antidiabetic regimens to glyburide tablets should be done conservatively and the initial daily dose should be 2.5 to 5 mg. When transferring patients from oral hypoglycemic agents other than chlorpropamide to glyburide tablets, no transition period and no initial or priming dose are necessary. When transferring patients from chlorpropamide, particular care should be exercised during the first two weeks because the prolonged retention of chlorpropamide in the body and subsequent overlapping drug effects may provoke hypoglycemia.

Patients Receiving Insulin

Some Type II diabetic patients being treated with insulin may respond satisfactorily to glyburide tablets. If the insulin dose is less than 20 units daily, substitution of glyburide tablets 2.5 to 5 mg as a single daily dose may be tried. If the insulin dose is between 20 and 40 units daily, the patient may be placed directly on glyburide tablets 5 mg daily as a single dose. If the insulin dose is more than 40 units daily, a transition period is required for conversion to glyburide tablets. In these patients, insulin dosage is decreased by 50% and glyburide tablets 5 mg daily is started. Please refer to Titration to Maintenance Dose for further explanation.

Titration to Maintenance Dose

The usual maintenance dose is in the range of 1.25 to 20 mg daily, which may be given as a single dose or in divided doses (see Dosage Interval). Dosage increases should be made in increments of no more than 2.5 mg at weekly intervals based upon the patient’s blood glucose response.

No exact dosage relationship exists between glyburide tablets and the other oral hypoglycemic agents. Although patients may be transferred from the maximum dose of other sulfonylureas, the maximum starting dose of 5 mg of glyburide tablets should be observed. A maintenance dose of 5 mg of glyburide tablets provides approximately the same degree of blood glucose control as 250 to 375 mg chlorpropamide, 250 to 375 mg tolazamide, 500 to 750 mg acetohexamide, or 1000 to 1500 mg tolbutamide.

When transferring patients receiving more than 40 units of insulin daily, they may be started on a daily dose of glyburide tablets 5 mg concomitantly with a 50% reduction in insulin dose. Progressive withdrawal of insulin and increase of glyburide in increments of 1.25 to 2.5 mg every 2 to 10 days is then carried out. During this conversion period when both insulin and glyburide are being used, hypoglycemia may rarely occur. During insulin withdrawal, patients should test their urine for glucose and acetone at least three times daily and report results to their physician. The appearance of persistent acetonuria with glycosuria indicates that the patient is a Type I diabetic who requires insulin therapy.

Concomitant Glyburide and Metformin Therapy

Glyburide tablets should be added gradually to the dosing regimen of patients who have not responded to the maximum dose of metformin monotherapy after four weeks (see Usual Starting Dose and Titration to Maintenance Dose). Refer to metformin package insert.

With concomitant glyburide and metformin 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 optimal dose of each drug needed to achieve this goal. With concomitant glyburide and metformin therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken (see PRECAUTIONS).

Maximum Dose

Daily doses of more than 20 mg are not recommended.

Dosage Interval

Once-a-day therapy is usually satisfactory. Some patients, particularly those receiving more than 10 mg daily, may have a more satisfactory response with twice-a-day dosage.

Specific Patient Populations

Glyburide is not recommended for use in pregnancy or for use in pediatric patients.

In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS).
Hydroxyzine Hydrochlori...

Hydroxyzine Hydrochloride

For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested: Adults, 50 mg to 100 mg q.i.d.; children under 6 years, 50 mg daily in divided doses; children over 6 years, 50 mg to 100 mg daily in divided doses.

For use in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses and in histamine-mediated pruritus: adults, 25 mg t.i.d. or q.i.d.; children under 6 years, 50 mg daily in divided doses; children over 6 years, 50 mg to 100 mg daily in divided doses.

As a sedative when used as a premedication and following general anesthesia: 50 mg to 100 mg in adults and 0.6 mg/kg of body weight in children.

When treatment is initiated by the intramuscular route of administration, subsequent doses may be administered orally.

As with all potent medication, the dosage should be adjusted according to the patient's response to therapy.
Hydralazine Hydrochlori...

Hydralazine Hydrochloride

Initiate therapy in gradually increasing dosages; adjust according to individual response. Start with 10 mg four times daily for the first 2 to 4 days, increase to 25 mg four times daily for the balance of the first week. For the second and subsequent weeks, increase dosage to 50 mg four times daily. For maintenance, adjust dosage to the lowest effective levels.

The incidence of toxic reactions, particularly the L.E. cell syndrome, is high in the group of patients receiving large doses of hydralazine hydrochloride tablets.

In a few resistant patients, up to 300 mg of hydralazine hydrochloride tablets daily may be required for a significant antihypertensive effect. In such cases, a lower dosage of hydralazine hydrochloride tablets combined with a thiazide and/or reserpine or a beta blocker may be considered. However, when combining therapy, individual titration is essential to ensure the lowest possible therapeutic dose of each drug.
Hydrochlorothiazide

Hydrochlorothiazide

For Control of Hypertension

The adult initial dose of hydrochlorothiazide capsules 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.
Metolazone

Metolazone

Effective dosage of metolazone tablets should be individualized according to indication and patient response. A single daily dose is recommended. Therapy with metolazone tablets should be titrated to gain an initial therapeutic response and to determine the minimal dose possible to maintain the desired therapeutic response.

Usual Single Daily Dosage Schedules

Suitable initial dosages will usually fall in the ranges given.

Edema of cardiac failure:
Metolazone tablets 5 to 20 mg once daily.
Edema of renal disease:
Metolazone tablets 5 to 20 mg once daily.
Mild to moderate essential hypertension:
Metolazone tablets 2.5 to 5 mg once daily. New patients- If considered desirable to switch patients currently on Zaroxolyn ® tablets and other formulations of metolazone that share its slow and incomplete bioavailability to Mykrox ®, the dose should be determined by titration starting at one tablet (0.5 mg) once daily and increasing to two tablets (1 mg) once daily if needed.
Treatment of Edematous States

The time interval required for the initial dosage to produce an effect may vary. Diuresis and saluresis usually begin within one hour and persist for 24 hours or longer. When a desired therapeutic effect has been obtained, it may be advisable to reduce the dose if possible. The daily dose depends on the severity of the patient's condition, sodium intake, and responsiveness. A decision to change the daily dose should be based on the results of thorough clinical and laboratory evaluations. If antihypertensive drugs or diuretics are given concurrently with metolazone tablets, more careful dosage adjustment may be necessary. For patients who tend to experience paroxysmal nocturnal dyspnea, it may be advisable to employ a larger dose to ensure prolongation of diuresis and saluresis for a full 24-hour period.

Treatment of Hypertension

The time interval required for the initial dosage regimen to show effect may vary from three or four days to three to six weeks in the treatment of elevated blood pressure. Doses should be adjusted at appropriate intervals to achieve maximum therapeutic effect.
Midodrine Hydrochloride...

Midodrine Hydrochloride

The recommended dose of midodrine hydrochloride tablets is 10 mg, 3 times daily. Dosing should take place during the daytime hours when the patient needs to be upright, pursuing the activities of daily life. A suggested dosing schedule of approximately 4-hour intervals is as follows: shortly before or upon arising in the morning, midday, and late afternoon (not later than 6 P.M.). Doses may be given in 3-hour intervals, if required, to control symptoms, but not more frequently. Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (about 45%) at this dose. In order to reduce the potential for supine hypertension during sleep, midodrine hydrochloride tablets should not be given after the evening meal or less than 4 hours before bedtime. Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established. Because of the risk of supine hypertension, midodrine hydrochloride tablets should be continued only in patients who appear to attain symptomatic improvement during initial treatment.

The supine and standing blood pressure should be monitored regularly, and the administration of midodrine hydrochloride tablets should be stopped if supine blood pressure increases excessively.

Because desglymidodrine is excreted renally, dosing in patients with abnormal renal function should be cautious; although this has not been systematically studied, it is recommended that treatment of these patients be initiated using 2.5 mg doses.

Dosing in children has not been adequately studied.

Blood levels of midodrine and desglymidodrine were similar when comparing levels in patients 65 or older vs. younger than 65 and when comparing males vs. females, suggesting dose modifications for these groups are not necessary.
Isoniazid

Isoniazid

-

NOTE -- For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: (1) the recommen- dations of the Advisory Council for the Elimination of Tuberculosis, published in the MMWR: vol 42; RR-4, 1993 and (2) Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children, American Journal of Respiratory and Critical Care Medicine: vol 149; 1359-1374, 1994.

For Treatment of Tuberculosis

Isoniazid is used in conjunction with other effective anti-tuberculosis agents. Drug susceptibility testing should be performed on the organisms initially isolated from all patients with newly diagnosed tuberculosis. If the bacilli becomes resistant, therapy must be changed to agents to which the bacilli are susceptible.

Usual Oral Dosage (depending on the regimen used):

Adults: 5 mg/kg up to 300 mg daily in a single dose; or 15 mg/kg up to 900 mg/day, two or

three times/week

Children: 10 - 15 mg/kg up to 300 mg daily in a single dose; or 20-40 mg/kg up to 900

mg/day, two or three times/week

Patients with Pulmonary Tuberculosis Without HIV Infection

There are 3 regimen options for the initial treatment of tuberculosis in children and adults:

Option 1: Daily isoniazid, rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of

isoniazid and rifampin daily or 2 to 3 times weekly. Ethambutol or streptomycin

should be added to the initial regimen until sensitivity to isoniazid and rifampin is

demonstrated. The addition of a fourth drug is optional if the relative prevalence of

isoniazid-resistant Mycobacteriumtuberculosis isolates in the community is less

than or equal to four percent.

Option 2: Daily isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol for 2

weeks followed by twice weekly administration of the same drugs for 6 weeks,

subsequently twice weekly isoniazid and rifampin for 16 weeks.

Option 3: Three times weekly with isoniazid, rifampin, pyrazinamide, and ethambutol or

streptomycin for 6 months.

* All regimen given twice weekly or 3 times weekly should be administered by directly observed therapy (see also Directly Observed Therapy).

The above treatment guidelines apply only when the disease is caused by organisms that are sus- ceptible to the standard antituberculous agents. Because of the impact of resistance to isoniazid and rifampin on the response to therapy, it is essential that physicians initiating therapy for tu- berculosis be familiar with the prevalence of drug resistance in their communities. It is suggested that ethambutol not be used in children whose visual acuity cannot be monitored.

Patients with Pulmonary Tuberculosis and HIV Infection

The response of the immunologically impaired host to treatment may not be as satisfactory as that of a person with normal host responsiveness. For this reason, therapeutic decisions for the impaired host must be individualized. Since patients co-infected with HIV may have problems with malabsorption, screening of antimycobacterial drug levels, especially in patients with ad- vanced HIV disease, may be necessary to prevent the emergence of MDRTB.

Patients with Extra Pulmonary Tuberculosis

The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease. Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective. Because of the insufficient data, military tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children should receive 12 month therapy.

Bacteriologic evaluation of Extra pulmonary tuberculosis may be limited by the relative in accessibility of the sites of disease. Thus, response to treatment often must be judged on the basis of clinical and radiographic findings.

The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease. Surgery may be necessary to obtain specimens for diagnosis and to treat such processes as constrictive pericarditis and spinal cord compression from Pott’s Disease. Corticosteroids have been shown to be of benefit in preventing cardiac constriction from tuberculous pericarditis and in decreasing the neurologic sequelae of all stages of tuberculosis meningitis, especially when administered early in the course of the disease.

Pregnant Women with Tuberculosis

The options listed above must be adjusted for the pregnant patient. Streptomycin interferes with in utero development of the ear and may cause congenital deafness. Routine use of pyrazinamide is also not recommended in pregnancy because of inadequate teratogenicity data. The initial treatment regimen should consist of isoniazid and rifampin. Ethambutol should be included unless primary isoniazid resistance is unlikely (isoniazid resistance rate documented to be less than 4%).

Treatment of Patients with Multi-Drug Resistant Tuberculosis (MDRTB)

Multiple-drug resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended.

Directly Observed Therapy (DOT)

A major cause of drug-resistant tuberculosis is patient noncompliance with treatment. The use of DOT can help assure patient compliance with drug therapy. DOT is the observation of the pa- tient by a health care provider or other responsible person as the patient ingests anti-tuberculosis medications. DOT can be achieved with daily, twice weekly or thrice weekly regimens, and is recommended for all patients.

For Preventative Therapy of Tuberculosis

Before isoniazid preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. Appropriate evaluations should be performed if Extra pulmonary tuberculosis is suspected.

Adults over 30 Kg: 300 mg per day in a single dose.

Infants and Children: 10 mg/kg (up to 300 mg daily) in a single dose. In situations where adherence with daily preventative therapy cannot be assured, 20-30 mg/kg (not to exceed 900 mg) twice weekly under the direct observation of a health care worker at the time of admin- istration8.

Continuous administration of isoniazid for a sufficient period is an essential part of the regimen because relapse rates are higher if chemotherapy is stopped prematurely. In the treatment of tu- berculosis, resistant organisms may multiply and the emergence of resistant organisms during the treatment may necessitate a change in the regimen.

For following patient compliance: the Potts-Cozart test9, a simple colorimetric6 method of checking for isoniazid in the urine, is a useful tool for assuring patient compliance, which is essential for effective tuberculosis control. Additionally, isoniazid test strips are also available

to check patient compliance.

Concomitant administration of pyridoxine (B6) is recommended in malnourished and in those predisposed to neuropathy (e.g., alcoholics and diabetics).
Loperamide Hydrochlorid...

Loperamide Hydrochloride

(1 capsule = 2 mg): Patients should receive appropriate fluid and electrolyte replacement as needed.

Acute Diarrhea

Adults

The recommended initial dose is 4 mg (two capsules) followed by 2 mg (one capsule) after each unformed stool. Daily dose should not exceed 16 mg (eight capsules). Clinical improvement is usually observed within 48 hours.

Children

In children 2 to 5 years of age (20 kg or less), the non-prescription liquid formulation of loperamide should be used; for ages 6 to 12, either loperamide hydrochloride capsules or the non-prescription liquid formulation of loperamide may be used. For children 2 to 12 years of age, the following schedule for capsules or liquid will usually fulfill initial dosage requirements:

Recommended First Day Dosage Schedule

Two to five years:

1 mg t.i.d. (3 mg daily dose)(13 to 20 kg)

Six to eight years:

2 mg b.i.d. (4 mg daily dose)(20 to 30 kg)

Eight to twelve years:

2 mg t.i.d. (6 mg daily dose)(greater than 30 kg)

Recommended Subsequent Daily Dosage

Following the first treatment day, it is recommended that subsequent loperamide hydrochloride doses (1 mg/10 kg body weight) be administered only after a loose stool. Total daily dosage should not exceed recommended dosages for the first day.

Chronic Diarrhea

Children

Although loperamide hydrochloride capsule has been studied in a limited number of children with chronic diarrhea; the therapeutic dose for the treatment of chronic diarrhea in a pediatric population has not been established.

Adults

The recommended initial dose is 4 mg (two capsules) followed by 2 mg (one capsule) after each unformed stool until diarrhea is controlled, after which the dosage of loperamide hydrochloride capsules should be reduced to meet individual requirements. When the optimal daily dosage has been established, this amount may then be administered as a single-dose or in divided doses.

The average daily maintenance dosage in clinical trials was 4 to 8 mg (two to four capsules). A dosage of 16 mg (eight capsules) was rarely exceeded. If clinical improvement is not observed after treatment with 16 mg per day for at least 10 days, symptoms are unlikely to be controlled by further administration. Loperamide hydrochloride capsule administration may be continued if diarrhea cannot be adequately controlled with diet or specific treatment.

Children Under 2 Years

The use of loperamide hydrochloride capsule in children under 2 years is not recommended. There have been rare reports of paralytic ileus associated with abdominal distention. Most of these reports occurred in the setting of acute dysentery, overdose, and with very young children less than 2 years of age.

Elderly

No formal pharmacokinetic studies were conducted in elderly subjects. However, there were no major differences reported in the drug disposition in elderly patients with diarrhea relative to young patients. No dosage adjustment is required for the elderly.

Renal Impairment

No pharmacokinetic data are available in patients with renal impairment. Since the metabolites and the unchanged drug are mainly excreted in the feces, no dosage adjustment is required for patients with renal impairment (see PRECAUTIONS).

Hepatic Impairment

Although no pharmacokinetic data are available in patients with hepatic impairment, loperamide hydrochloride capsule should be used with caution in such patients because of reduced first pass metabolism (see PRECAUTIONS).
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 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).
Mycophenolate Mofetil C...

Mycophenolate Mofetil Capsule Mycophenolate Mofetil

Renal Transplantation

Adults

A dose of 1 g administered orally twice a day (daily dose of 2 g) is recommended for use in renal transplant patients. Although a dose of 1.5 g administered twice daily (daily dose of 3 g) was used in clinical trials and was shown to be safe and effective, no efficacy advantage could be established for renal transplant patients. Patients receiving 2 g/day of mycophenolate mofetil demonstrated an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil.

Pediatrics (3 Months to 18 years of Age)

The recommended dose of mycophenolate mofetil oral suspension is 600 mg/m2 administered twice daily (up to a maximum daily dose of 2 g/10 mL oral suspension). Patients with a body surface area of 1.25 m2 to 1.5 m2 may be dosed with mycophenolate mofetil capsules at a dose of 750 mg twice daily (1.5 g daily dose). Patients with a body surface area > 1.5 m2 may be dosed with mycophenolate mofetil capsules or tablets at a dose of 1 g twice daily (2 g daily dose).

Cardiac Transplantation

Adults

A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult cardiac transplant patients.

Hepatic Transplantation

Adults

A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult hepatic transplant patients.

Mycophenolate Mofetil Capsules and Tablets

The initial oral dose of mycophenolate mofetil should be given as soon as possible following renal, cardiac or hepatic transplantation. Food had no effect on MPA AUC, but has been shown to decrease MPA Cmax by 40%. Therefore, it is recommended that mycophenolate mofetil be administered on an empty stomach. However, in stable renal transplant patients, mycophenolate mofetil may be administered with food if necessary.

Patients should be instructed to take a missed dose as soon as they remember, except if it is near the next scheduled dose, and then continue to take mycophenolate mofetil at the usual times.

Patients with Hepatic Impairment

No dose adjustments are recommended for renal patients with severe hepatic parenchymal disease. However, it is not known whether dose adjustments are needed for hepatic disease with other etiologies (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

No data are available for cardiac transplant patients with severe hepatic parenchymal disease.

Geriatrics

The recommended oral dose of 1 g bid for renal transplant patients, 1.5 g bid for cardiac transplant patients and 1.5 g bid administered orally in hepatic transplant patients is appropriate for elderly patients (see PRECAUTIONS: Geriatric Use).

Dosage Adjustments

In renal transplant patients with severe chronic renal impairment (GFR < 25 mL/min/1.73 m2) outside the immediate post-transplant period, doses of mycophenolate mofetil greater than 1 g administered twice a day should be avoided. These patients should also be carefully observed. No dose adjustments are needed in renal transplant patients experiencing delayed graft function postoperatively (see CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: Patients with Renal Impairment).

No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. Mycophenolate mofetil may be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

If neutropenia develops (ANC < 1.3 x 103/µL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed and the patient managed appropriately (see WARNINGS: Neutropenia, ADVERSE REACTIONS and PRECAUTIONS: Laboratory Tests).
Hydrocodone Bitartrate ...

Hydrocodone Bitartrate And Acetaminophen

Dosage should be adjusted according to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

Hydrocodone Bitartrate and Acetaminophen Tablets, USP 5 mg/325 mg

The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 12 tablets.

Hydrocodone Bitartrate and Acetaminophen Tablets, USP 7.5 mg/325 mg

The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.

Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/325 mg

The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.

Hydrocodone Bitartrate and Acetaminophen Tablets, USP 5 mg/325 mg

The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 12 tablets.

Hydrocodone Bitartrate and Acetaminophen Tablets, USP 7.5 mg/325 mg

The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.

Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/325 mg

The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.
Ziprasidone Hydrochlori...

Ziprasidone Hydrochloride

2.1 Schizophrenia

Dose Selection

Ziprasidone hydrochloride capsules should be administered at an initial daily dose of 20 mg twice daily with food. In some patients, daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg twice daily. Dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, as steady-state is achieved within 1 to 3 days. In order to ensure use of the lowest effective dose, patients should ordinarily be observed for improvement for several weeks before upward dosage adjustment.

Efficacy in schizophrenia was demonstrated in a dose range of 20 mg to 100 mg twice daily in short-term, placebo-controlled clinical trials. There were trends toward dose-response within the range of 20 mg to 80 mg twice daily, but results were not consistent. An increase to a dose greater than 80 mg twice daily is not generally recommended. The safety of doses above 100 mg twice daily has not been systematically evaluated in clinical trials [see Clinical Studies (14.1)].

Maintenance Treatment

While there is no body of evidence available to answer the question of how long a patient treated with ziprasidone should remain on it, a maintenance study in patients who had been symptomatically stable and then randomized to continue ziprasidone or switch to placebo demonstrated a delay in time to relapse for patients receiving ziprasidone hydrochloride capsules [see Clinical Studies (14.1)]. No additional benefit was demonstrated for doses above 20 mg twice daily. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.4 Dosing in Special Populations

Oral

Dosage adjustments are generally not required on the basis of age, gender, race or renal or hepatic impairment. Ziprasidone hydrochloride capsules are not approved for use in children or adolescents.

Mylan Institutional Inc.

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