Cardinal Health

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do not take more than directed (see Liver warning) adults and children 12 years and over take 2 geltabs every 6 hours as needed do not take more than 8 geltabs in 24 hours children under 12 years do not use this adult Extra Strength product in children under 12 years of age; this will provide more than the recommended dose (overdose) and may cause liver damage

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do not give more than directed (see Liver warning) shake well before using find right dose on chart. If possible, use weight to dose; otherwise, use age. use only enclosed dosing cup designed for use with this product. Do not use any other dosing device. if needed, repeat dose every 4 hours while symptoms last do not give more than 5 times in 24 hours do not give for more than 5 days unless directed by a doctor this product does not contain directions or complete warnings for adult use Weight(lb) Age(yr) Dose (tsp or mL) under 24 under 2 years ask a doctor 24-35 2–3 years 1 tsp or 5 mL 36–47 4–5 years 1 1/2 tsp or 7.5 mL 48–59 6–8 years 2 tsp or 10 mL 60-71 9–10 years 2 1/2 tsp or 12.5 mL 72-95 11 years 3 tsp or 15 mL

Attention: use only enclosed dosing cup specifically designed for use with this product. Do not use any other dosing device.

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2.1 Hypertension

Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect.

Use with diuretics in adults

If blood pressure is not controlled with lisinopril alone, a low dose of a diuretic may be added (eg, hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of lisinopril.

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 tablet USP is 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, 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 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 USP 5 mg orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for at least six weeks.

Initiate therapy with 2.5 mg in patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mm Hg) during the first 3 days after the infarct [see WARNINGS AND PRECAUTIONS (5.4)]. If hypotension occurs (systolic blood pressure ≤ 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) lisinopril should be withdrawn.

2.4 Dose in Patients with Renal Impairment

No dose adjustment of lisinopril 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 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)].

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Instructions for Use/Handling Ondansetron Orally Disintegrating Tablets 

Do not attempt to push ondansetron orally disintegrating tablets, USP through the foil backing. With dry hands, PEEL BACK the foil backing of 1 blister and GENTLY remove the tablet. IMMEDIATELY place the ondansetron orally disintegrating tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary.

Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy 

The recommended adult oral dosage of ondansetron 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 orally disintegrating tablet, USP given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8-mg ondansetron orally disintegrating tablet, USP 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 orally disintegrating tablet, USP given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4-mg ondansetron orally disintegrating tablet, USP should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.

Geriatric Use 

The dosage is the same as for the general population.

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

The recommended oral dosage is one 8 mg ondansetron orally disintegrating tablet, USP given 3 times a day.

For total body irradiation

One 8-mg ondansetron orally disintegrating tablet, USP should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.

For single high-dose fraction radiotherapy to the abdomen

One 8-mg ondansetron orally disintegrating tablet, USP should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.

For daily fractionated radiotherapy to the abdomen

One 8-mg ondansetron orally disintegrating tablet, USP 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 orally disintegrating tablets, USP, 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 orally disintegrating tablets, USP 1 hour before induction of anesthesia.

Pediatric Use 

There is no experience with the use of ondansetron orally disintegrating tablets, USP 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.

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Carefully consider the potential benefits and risks of naproxen tablets and other treatment options before deciding to use naproxen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with naproxen tablets, the dose and frequency should be adjusted to suit an individual patient's needs.

Different dose strengths and formulations (i.e., tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although naproxen tablets, naproxen suspension, naproxen delayed-release tablets, and naproxen sodium tablets all circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium and within 1 hour in patients taking naproxen. Because naproxen delayed-release tablets dissolve in the small intestine rather than in the stomach, the absorption of the drug is delayed compared to the other naproxen formulations (see CLINICAL PHARMACOLOGY).

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

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

Patients With Moderate to Severe Renal Impairment

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

Rheumatoid Arthritis, Osteoarthritis, and Ankylosing Spondylitis

Naproxen Tablets 250 mg   twice daily or 375 mg twice daily or 500 mg twice daily

During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis

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

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

Because the sodium salt of naproxen is more rapidly absorbed, naproxen sodium is recommended for the management of acute painful conditions when prompt onset of pain relief is desired. Naproxen tablets may also be used.

For the relief of mild to moderate pain, primary dysmenorrhea, and acute tendonitis and bursitis, the recommended starting dose of naproxen is 500 mg given orally, followed by 500 mg given orally every 12 hours or 250 mg given orally every 6 to 8 hours as required. The initial total daily dose should not exceed 1250 mg of naproxen. Thereafter, the total daily dose should not exceed 1000 mg of naproxen (see CLINICALPHARMACOLOGY and INDICATIONS AND USAGE).

Acute Gout

The recommended starting dose is 750 mg of naproxen followed by 250 mg every 8 hours until the attack has subsided (see CLINICAL PHARMACOLOGY).

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Treatment of Erosive Esophagitis

The recommended adult oral dose is 40 mg given once daily for up to 8 weeks. For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium may be considered (see INDICATIONS AND USAGE).

Maintenance of Healing of Erosive Esophagitis

The recommended adult oral dose is one pantoprazole sodium 40 mg delayed-release tablet, taken daily (see CLINICAL PHARMACOLOGY, Clinical Studies).

Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

The dosage of pantoprazole sodium in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult starting dose is 40 mg twice daily. 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. Some patients have been treated continuously with pantoprazole sodium for more than 2 years.

No dosage adjustment is necessary in patients with renal impairment, hepatic impairment, or for elderly patients. Doses higher than 40 mg/day have not been studied in hepatically-impaired patients. No dosage adjustment is necessary in patients undergoing hemodialysis.

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.

Patients should be cautioned that pantoprazole sodium delayed-release tablets should not be split, chewed or crushed.

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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 Trials: Active Duodenal Ulcer). Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in U.S. studies, and several foreign trials have shown that 100 mg twice daily is as effective as the 150 mg dose. Antacid should be given as needed for relief of pain (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Maintenance of Healing of Duodenal Ulcers

The current recommended adult oral dosage is 150 mg 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 have been established in the age-group of 1 month to 16 years. There is insufficient information about the pharmacokinetics of ranitidine in neonatal patients (less than 1 month of age) to make dosing recommendations.

The following three 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).

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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.

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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.

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.

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).

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Directions

■ do not take more than directed

■ the smallest effective dose should be used

■ do not take longer than 10 days, unless directed by a doctor (see Warnings)

■ drink a full glass of water with each dose

Adults and children 12 years ■ take 1 caplet every 8 to 12 hours while symptoms last

and older ■ for the first dose you may take 2 caplets within the first hour

■ do not exceed 2 caplets in any 8- to 12-hour period

■ do not exceed 3 caplets in a 24-hour period

Children under 12 years ■ ask a doctor

Other information

■ each caplet contains: sodium 20 mg

■ store at 20-25°C (68-77°F). Avoid high humidity and excessive heat above 40°C (104°F).

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Clonazepam 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 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 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 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).

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Hypertension

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 in single or divided doses, whether used alone or added to a diuretic. 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 1 week of therapy. The effective dosage range of Metoprolol tartrate tablets is 100 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. The dosage may be gradually increased 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 to 400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, the dosage should be reduced gradually 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, treatment with metoprolol tartrate can be initiated 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.

Treatment in this early phase should begin with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; the injections should be given at approximately 2-minute intervals. During the intravenous administration of metoprolol, blood pressure, heart rate, and electrocardiogram should be carefully monitored.

In patients who tolerate the full intravenous dose (15 mg), metoprolol tartrate tablets, 50 mg every 6 hours, should be initiated 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, patients should receive a maintenance dosage of 100 mg twice daily (see Late Treatment below).

Patients who appear not to tolerate the full intravenous dose should be started 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, treatment with metoprolol should be discontinued (see WARNINGS).

Late Treatment

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 should be started on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Therapy should be continued 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.

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Motion Sickness: The initial dose of 25 to 50 mg meclizine hydrochloride, 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.

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Hypertension

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 in single or divided doses, whether used alone or added to a diuretic. 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. The effective dosage range 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. The dosage may be gradually increased 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, the dosage should be reduced gradually 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, treatment with metoprolol tartrate tablets can be initiated 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.

Treatment in this early phase should begin with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; the injections should be given at approximately 2 minute intervals. During the intravenous administration of metoprolol, blood pressure, heart rate, and electrocardiogram should be carefully monitored.

In patients who tolerate the full intravenous dose (15 mg), metoprolol tartrate tablets, 50 mg every 6 hours, should be initiated 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, patients should receive a maintenance dosage of 100 mg twice daily (see Late Treatment below).

Patients who appear not to tolerate the full intravenous dose should be started 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, treatment with metoprolol should be discontinued (see WARNINGS).

Late Treatment

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 should be started on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Therapy should be continued 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.

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2.1 General Instructions

Carefully consider the potential benefits and risks of meloxicam tablets USP and other treatment options before deciding to use meloxicam tablets USP. 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 USP, adjust the dose to suit an individual patient's needs.

In adults, the maximum recommended daily oral dose of meloxicam tablets USP 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 USP 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 USP 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 USP is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.

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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 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day.

For the subset of patients for whom rapid onset of analgesic effect is required and for whom the benefits outweigh the risk of discontinuation due to adverse events associated with higher initial doses, tramadol hydrochloride tablets 50 mg to 100 mg can be administered as needed for pain relief every four to six hours, not to exceed 400 mg per day.

Individualization of Dose

Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Studies with tramadol in adults have shown that starting at the lowest possible dose and titrating upward will result in fewer discontinuations and increased tolerability.

In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride tablets be increased to 12 hours, with a maximum daily dose of 200 mg. Since only 7% of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis. The recommended dose for adult patients with cirrhosis is 50 mg every 12 hours. In general, dose selection for an elderly patient over 65 years old should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. For elderly patients over 75 years old, total dose should not exceed 300 mg/day.

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adults and children 6 years and over 1 tablet daily; not more than 1 tablet in 24 hours children under 6 years of age ask a doctor consumers with liver or kidney disease ask a doctor

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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.

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Initial Treatment Dosage for Adults

Major Depressive Disorder–Sertraline hydrochloride treatment should be administered at a dose of 50 mg once daily.

While a relationship between dose and effect has not been established for major depressive disorder patients were dosed in a range of 50-200 mg/day in the clinical trials demonstrating the effectiveness of sertraline hydrochloride for the treatment of this indication. Consequently, a dose of 50 mg, administered once daily, is recommended as the initial therapeutic dose. Patients not responding to a 50 mg dose may benefit from dose increases up to a maximum of 200 mg/day. Given the 24 hour elimination half-life of sertraline hydrochloride, dose changes should not occur at intervals of less than 1 week.

Premenstrual Dysphoric Disorder– Sertraline hydrochloride treatment should be initiated with a dose of 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment.

While a relationship between dose and effect has not been established for PMDD, patients were dosed in the range of 50-150 mg/day with dose increases at the onset of each new menstrual cycle (see Clinical Trials under CLINICAL PHARMACOLOGY). Patients not responding to a 50 mg/day dose may benefit from dose increases (at 50 mg increments/menstrual cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100 mg/day dose has been established with luteal phase dosing, a 50 mg/day titration step for three days should be utilized at the beginning of each luteal phase dosing period.

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

Maintenance/Continuation/Extended Treatment

Major Depressive Disorder–It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy beyond response to the acute episode. Systematic evaluation of sertraline hydrochloride has demonstrated that its antidepressant efficacy is maintained for periods of up to 44 weeks following 8 weeks of initial treatment at a dose of 50-200 mg/day (mean dose of 70 mg/day) (see Clinical Trials under CLINICAL PHARMACOLOGY). It is not known whether the dose of sertraline hydrochloride needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Premenstrual Dysphoric Disorder–The effectiveness of sertraline hydrochloride in long-term use, that is, for more than 3 menstrual cycles, has not been systematically evaluated in controlled trials. However, as women commonly report that symptoms worsen with age until relieved by the onset of menopause, it is reasonable to consider continuation of a responding patient. Dosage adjustments, which may include changes between dosage regimens (e.g., daily throughout the menstrual cycle versus during the luteal phase of the menstrual cycle), may be needed to maintain the patient on the lowest effective dosage and patients should be periodically reassessed to determine the need for continued treatment.

Switching 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 hydrochloride. In addition, at least 14 days should be allowed after stopping sertraline hydrochloride 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 hydrochloride and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with sertraline hydrochloride during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering sertraline hydrochloride in the third trimester.

Discontinuation of Treatment with sertraline hydrochloride

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

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Initial Treatment

The recommended starting dose for mirtazapine tablet, USP is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine tablets, USP in the treatment of major depressive disorder, the effective dose range was generally 15-45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine tablet, USP 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 tablet, USP has an elimination half-life of approximately 20-40 hours; therefore, dose changes should not be made at intervals of less than one to two 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 tablet, USP 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 tablet, USP 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, USP has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8–12 weeks of initial treatment at a dose of 15–45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine tablet, USP 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 Patients To or From a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with mirtazapine tablet, USP. In addition, at least 14 days should be allowed after stopping mirtazapine tablet, USP before starting an MAOI.

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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.

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Adults:

The usual dose is one 5-mg tablet two to three times a day. The maximum recommended dose is one 5-mg tablet four times a day. A lower starting dose of 2.5 mg two or three times a day is recommended for the frail elderly.

Pediatric patients over 5 years of age:

The usual dose is one 5-mg tablet two times a day. The maximum recommended dose is one 5-mg tablet three times a day.

Adults:

The usual dose is one 5-mg tablet two to three times a day. The maximum recommended dose is one 5-mg tablet four times a day. A lower starting dose of 2.5 mg two or three times a day is recommended for the frail elderly.

Pediatric patients over 5 years of age:

The usual dose is one 5-mg tablet two times a day. The maximum recommended dose is one 5-mg tablet three times a day.

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Initial Treatment

Citalopram HBr should be administered at an initial dose of 20 mg once daily, generally with an increase to a dose of 40 mg/day. Dose increases should usually occur in increments of 20 mg at intervals of no less than one week. Although certain patients may require a dose of 60 mg/day, the only study pertinent to dose response for effectiveness did not demonstrate an advantage for the 60 mg/day dose over the 40 mg/day dose; doses above 40 mg are therefore not ordinarily recommended.

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

Special Populations

20 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment, with titration to 40 mg/day only for nonresponding patients.

No dosage adjustment is necessary for patients with mild or moderate renal impairment. Citalopram HBr should be used with caution in patients with severe renal impairment.

Treatment of Pregnant Women During the Third Trimester

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

Maintenance Treatment

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

Discontinuation of Treatment with Citalopram HBr

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

Switching Patients To or From a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of citalopram HBr therapy. Similarly, at least 14 days should be allowed after stopping citalopram HBr before starting an MAOI (see CONTRAINDICATIONSand WARNINGS).

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Glaucoma

Acetazolamide should be used as an adjunct to the usual therapy. The dosage employed in the treatment of chronic simple (open-angle) glaucoma ranges from 250 mg to 1 g of acetazolamide per 24 hours, usually in divided doses for amounts over 250 mg. It has usually been found that a dosage in excess of 1 g per 24 hours does not produce an increased effect. In all cases, the dosage should be adjusted with careful individual attention both to symptomatology and ocular tension. Continuous supervision by a physician is advisable.

In treatment of secondary glaucoma and in the preoperative treatment of some cases of acute congestive (closed-angle) glaucoma, the preferred dosage is 250 mg every four hours, although some cases have responded to 250 mg twice daily on short-term therapy. In some acute cases, it may be more satisfactory to administer an initial dose of 500 mg followed by 125 or 250 mg every four hours depending on the individual case. A complementary effect has been noted when acetazolamide has been used in conjunction with miotics or mydriatics as the case demanded.

Epilepsy

It is not clearly known whether the beneficial effects observed in epilepsy are due to direct inhibition of carbonic anhydrase in the central nervous system or whether they are due to the slight degree of acidosis produced by the divided dosage. The best results to date have been seen in petit mal in children. Good results, however, have been seen in patients, both children and adult, in other types of seizures such as grand mal, mixed seizure patterns, myoclonic jerk patterns, etc. The suggested total daily dose is 8 to 30 mg per kg in divided doses. Although some patients respond to a low dose, the optimum range appears to be from 375 to 1000 mg daily. However, some investigators feel that daily doses in excess of 1 g do not produce any better results than a 1 g dose. When acetazolamide tablets are given in combination with other anticonvulsants, it is suggested that the starting dose should be 250 mg once daily in addition to the existing medications. This can be increased to levels as indicated above.

The change from other medications to acetazolamide should be gradual and in accordance with usual practice in epilepsy therapy.

Congestive Heart Failure

For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg/kg). If, after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney recovery by skipping medication for a day. Acetazolamide tablets yield best diuretic results when given on alternate days, or for two days alternating with a day of rest.

Failures in therapy may be due to overdosage or too frequent dosage. The use of acetazolamide does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction.

Drug-Induced Edema

Recommended dosage is 250 to 375 mg of acetazolamide once a day for one or two days, alternating with a day of rest.

Acute Mountain Sickness

Dosage is 500 mg to 1000 mg daily, in divided doses. In circumstances of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable to initiate dosing 24 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms.

Note: The dosage recommendations for glaucoma and epilepsy differ considerably from those for congestive heart failure, since the first two conditions are not dependent upon carbonic anhydrase inhibition in the kidney which requires intermittent dosage if it is to recover from the inhibitory effect of the therapeutic agent.

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Ampicillin and Sulbactam for Injection, USP may be administered by either the IV or the IM routes.

For IV administration, the dose can be given by slow intravenous injection over at least 10 to 15 minutes or can also be delivered in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

Ampicillin and Sulbactam for Injection, USP may be administered by deep intramuscular injection (see Preparation for Intramuscular Injection).

The recommended adult dosage of Ampicillin and Sulbactam for Injection, USP is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of Ampicillin and Sulbactam for Injection, USP and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older

The recommended daily dose of Ampicillin and Sulbactam for Injection, USP in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of Ampicillin and Sulbactam for Injection, USP, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection, USP administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous Ampicillin and Sulbactam for Injection, USP (see CLINICAL STUDIES).

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of Ampicillin and Sulbactam for Injection, USP in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin and Sulbactam for Injection, USP Dosage Guide For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2 Ampicillin/Sulbactam Half-Life (Hours) Recommended Ampicillin and Sulbactam for Injection, USP Dosage ≥30 1 1.5 to 3 g q 6h to q 8h 15 to 29 5 1.5 to 3 g q 12h 5 to 14 9 1.5 to 3 g q 24h

When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

Males weight (kg) ×(140 - age) 72 × serum creatinine Females 0.85 × above value

COMPATIBILITY, RECONSTITUTION AND STABILITY:

Ampicillin and Sulbactam for Injection, USP sterile powder is to be stored at 20o to 25oC (68o to 77oF) [see USP Controlled Room Temperature] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam for Injection, USP and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

DIRECTIONS FOR USE:

General Dissolution Procedures

Ampicillin and Sulbactam for Injection, USP sterile powder for intravenous and intramuscular use may be reconstituted with any of the compatible diluents described in this insert. Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization.

Preparation for Intravenous Use

1.5 gram and 3.0 gram vials: Initially, vials for intravenous use may be reconstituted with Sterile Water for Injection to yield solutions containing 375 mg Ampicillin and Sulbactam for Injection, USP per mL (250 mg ampicillin/125 mg sulbactam per mL). An appropriate volume should then be immediately diluted with the following suitable parenteral diluents to yield solutions containing 3 to 45 mg Ampicillin and Sulbactam for Injection, USP per mL (2 to 30 mg ampicillin/1 to 15 mg sulbactam/per mL). Reconstitution of Ampicillin and Sulbactam for Injection, USP at the specified concentrations, with these diluents provides stable solutions for the time periods indicated in the following table: (After the indicated time periods, any unused portions of solutions should be discarded.)

Diluent Maximum Concentration (mg/mL) Ampicillin and Sulbactam for Injection, USP Use Periods Sterile Water for Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 0.9% Sodium Chloride Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 5% Dextrose injection 30 (20/10) 2 hrs @ 25°C 30 (20/10) 4 hrs @ 4°C 3 (2/1) 4 hrs @ 25°C Lactated Ringer’s Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 24 hrs @ 4°C M/6 Sodium Lactate Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 8 hrs @ 4°C 5% Dextrose in 0.45% Saline 3 (2/1) 4 hrs @ 25°C 15 (10/5) 4 hrs @ 4°C 10% Invert Sugar 3 (2/1) 4 hrs @ 25°C 30 (20/10) 3 hrs @ 4°C

Preparation for Intramuscular Injection

1.5 gram and 3 gram vials: Vials for intramuscular use may be reconstituted with Sterile Water for Injection USP, 0.5% Lidocaine Hydrochloride Injection USP or 2% Lidocaine Hydrochloride Injection USP. Consult the following table for recommended volumes to be added to obtain solutions containing 375 mg Ampicillin and Sulbactam per mL (250 mg ampicillin/125 mg sulbactam per mL). Note: Use only freshly prepared solutions and administer within one hour after preparation.

Ampicillin and Sulbactam for Injection, USP Vial Size Volume of Diluent to be Added Withdrawal Volume* 1.5 g 3.2 mL 4 mL 3 g 6.4 mL 8 mL

*There is sufficient excess present to allow withdrawal and administration of the stated volumes.

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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.

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.

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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.)

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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 (diclofenac sodium enteric-coated tablets; diclofenac sodium extended-release tablets; diclofenac potassium immediate-release tablets) are not necessarily bioequivalent even if the milligram strength is the same.

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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.

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.

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The dosage should be initiated at a low level and increased gradually, noting the clinical response and any evidence of intolerance. Occurrence of drowsiness may require the administration of a major portion of the daily dose at bedtime or a reduction of dosage. Trazodone Hydrochloride Tablets USP should be taken shortly after a meal or light snack. Symptomatic relief may be seen during the first week, with optimal antidepressant effects typically evident within two weeks. Twenty-five percent of those who respond to Trazodone Hydrochloride Tablets USP require more than two weeks (up to four weeks) of drug administration.

Usual Adult Dosage

An initial dose of 150 mg/day in divided doses is suggested. The dose may be increased by 50 mg/day every three to four days. The maximum dose for outpatients usually should not exceed 400 mg/day in divided doses. Inpatients (i.e., more severely depressed patients) may be given up to but not in excess of 600 mg/day in divided doses.

Maintenance

Dosage during prolonged maintenance therapy should be kept at the lowest effective level. Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response.

Although there has been no systematic evaluation of the efficacy of Trazodone Hydrochloride Tablets USP beyond 6 weeks, it is generally recommended that a course of antidepressant drug treatment should be continued for several months.

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Since both the 250-mg and 500-mg tablets of AUGMENTIN contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250-mg tablets of AUGMENTIN are not equivalent to one 500-mg tablet of AUGMENTIN; therefore, two 250-mg tablets of AUGMENTIN should not be substituted for one 500-mg tablet of AUGMENTIN.

Dosage

Adults

 The usual adult dose is one 500-mg tablet of AUGMENTIN every 12 hours or one 250-mg tablet of AUGMENTIN every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 875-mg tablet of AUGMENTIN every 12 hours or one 500-mg tablet of AUGMENTIN every 8 hours.

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of <30 mL/min. should not receive the 875-mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min. should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a less than 10 mL/min. glomerular filtration rate should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. (See WARNINGS.)

Pediatric Patients

Pediatric patients weighing 40 kg or more should be dosed according to the adult recommendations.

Due to the different amoxicillin to clavulanic acid ratios in the 250-mg tablet of AUGMENTIN (250/125) versus the 250-mg chewable tablet of AUGMENTIN (250/62.5), the 250-mg tablet of AUGMENTIN should not be used until the pediatric patient weighs at least 40 kg or more.

Administration

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

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There is considerable variation from patient to patient in the amount of medication required for treatment. As with all drugs used to treat schizophrenia, dosage should be individualized according to the needs and response of each patient. Dosage adjustments, either upward or downward, should be carried out as rapidly as practicable to achieve optimum therapeutic control.

To determine the initial dosage, consideration should be given to the patient's age, severity of illness, previous response to other antipsychotic drugs, and any concomitant medication or disease state. Debilitated or geriatric patients, as well as those with a history of adverse reactions to antipsychotic drugs, may require less haloperidol. The optimal response in such patients is usually obtained with more gradual dosage adjustments and at lower dosage levels.

Parenteral medication, administered intramuscularly in doses of 2 to 5 mg, is utilized for prompt control of the acutely agitated schizophrenic patient with moderately severe to very severe symptoms. Depending on the response of the patient, subsequent doses may be given, administered as often as every hour, although 4 to 8 hour intervals may be satisfactory.

Controlled trials to establish the safety and effectiveness of intramuscular administration in children have not been conducted.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Switchover Procedure

An oral form should supplant the injectable as soon as practicable. In the absence of bioavailability studies establishing bioequivalence between these two dosage forms the following guidelines for dosage are suggested. For an initial approximation of the total daily dose required, the parenteral dose administered in the preceding 24 hours may be used. Since this dose is only an initial estimate, it is recommended that careful monitoring of clinical signs and symptoms, including clinical efficacy, sedation, and adverse effects, be carried out periodically for the first several days following the initiation of switchover. In this way, dosage adjustments, either upward or downward, can be quickly accomplished. Depending on the patient's clinical status, the first oral dose should be given within 12 to 24 hours following the last parenteral dose.

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Neurontin is given orally with or without food. Patients should be informed that, should they break the scored 600 or 800 mg tablet in order to administer a half-tablet, they should take the unused half-tablet as the next dose. Half-tablets not used within several days of breaking the scored tablet should be discarded.

If Neurontin dose is reduced, discontinued or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

Postherpetic Neuralgia

In adults with postherpetic neuralgia, Neurontin therapy may be initiated as a single 300-mg dose on Day 1, 600 mg/day on Day 2 (divided BID), and 900 mg/day on Day 3 (divided TID). The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided TID). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range. Additional benefit of using doses greater than 1800 mg/day was not demonstrated.

Epilepsy

Neurontin is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in pediatric patients below the age of 3 years has not been established.

Patients >12 years of age: The effective dose of Neurontin is 900 to 1800 mg/day and given in divided doses (three times a day) using 300 or 400 mg capsules, or 600 or 800 mg tablets. The starting dose is 300 mg three times a day. If necessary, the dose may be increased using 300 or 400 mg capsules, or 600 or 800 mg tablets three times a day up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the TID schedule should not exceed 12 hours.

Pediatric Patients Age 3–12 years: The starting dose should range from 10–15 mg/kg/day in 3 divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of Neurontin in patients 5 years of age and older is 25–35 mg/kg/day and given in divided doses (three times a day). The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (three times a day) (see CLINICAL PHARMACOLOGY, Pediatrics.) Neurontin may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations. Dosages up to 50 mg/kg/day have been well-tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize Neurontin therapy. Further, because there are no significant pharmacokinetic interactions among Neurontin and other commonly used antiepileptic drugs, the addition of Neurontin does not alter the plasma levels of these drugs appreciably.

If Neurontin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

Dosage in Renal Impairment

Creatinine clearance is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance (CCr) can be reasonably well estimated using the equation of Cockcroft and Gault:

                for females CCr=(0.85)(140-age)(weight)/[(72)(SCr)]

                for males CCr=(140-age)(weight)/[(72)(SCr)]

where age is in years, weight is in kilograms and SCr is serum creatinine in mg/dL.

Dosage adjustment in patients ≥12 years of age with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication).

TABLE 5. Neurontin Dosage Based on Renal Function Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen(mg) * For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive). † Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table. ≥60 900–3600 300 TID 400 TID 600 TID 800 TID 1200 TID >30–59 400–1400 200 BID 300 BID 400 BID 500 BID 700 BID >15–29 200–700 200 QD 300 QD 400 QD 500 QD 700 QD 15* 100–300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)† Hemodialysis 125† 150† 200† 250† 350†

The use of Neurontin in patients <12 years of age with compromised renal function has not been studied.

Dosage in Elderly

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

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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.

In a few resistant patients, up to 300 mg of hydralazine daily may be required for a significant antihypertensive effect. In such cases, a lower dosage of hydralazine 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.

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2.1 Dosage in Adult Patients with Normal Renal Function

The usual dose of LEVAQUIN® Tablets or Oral Solution is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1. The usual dose of LEVAQUIN® Injection is 250 mg or 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes 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 ≥ 50mL/min) Type of Infection* Dosed Every 24 hours Duration (days)† * 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 LEVAQUIN ® 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 (5.9), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged LEVAQUIN ® therapy should only be used when the benefit outweighs the risk. Nosocomial Pneumonia 750 mg 7–14 Community Acquired Pneumonia‡ 500 mg 7–14 Community Acquired Pneumonia§ 750 mg 5 Acute Bacterial Sinusitis 750 mg 5 500 mg 10–14 Acute Bacterial Exacerbation of Chronic Bronchitis 500 mg 7 Complicated Skin and Skin Structure Infections (SSSI) 750 mg 7–14 Uncomplicated SSSI 500 mg 7–10 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 ageÞ,ß Pediatric patients < 50 kg and ≥ 6 months of ageÞ,ß 500 mg  see 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 Type of Infection* Dose Freq. Once every Duration† * 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 LEVAQUIN ® 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 (5.9), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged LEVAQUIN ® therapy should only be used when the benefit outweighs the risk. Inhalational Anthrax (post-exposure)‡,§ Pediatric patients > 50 kg and ≥ 6 months of age 500 mg 24 hr 60 days§ Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg(not to exceed 250 mg per dose) 12 hr 60 days§

2.3 Dosage Adjustment in Adults with Renal Impairment

Administer LEVAQUIN® 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 Clearance20 to 49 mL/min Creatinine Clearance10 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

LEVAQUIN® Tablets and Oral Solution

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

LEVAQUIN® Injection

LEVAQUIN® Injection should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see Dosage and Administration (2.6)].

2.5 Administration Instructions

Food and LEVAQUIN® Tablets and Oral Solution

LEVAQUIN® Tablets can be administered without regard to food. It is recommended that LEVAQUIN® Oral Solution be taken 1 hour before or 2 hours after eating.

LEVAQUIN® Injection

Caution: Rapid or bolus intravenous infusion of LEVAQUIN® has been associated with hypotension and must be avoided. LEVAQUIN® Injection should be infused intravenously slowly over a period of not less than 60 or 90 minutes, depending on the dosage. LEVAQUIN® Injection should be administered only by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

Hydration for Patients Receiving LEVAQUIN® Tablets, Oral Solution, and Injection

Adequate hydration of patients receiving oral or intravenous LEVAQUIN® 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)].

2.6 Preparation of Intravenous Product

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Because only limited data are available on the compatibility of LEVAQUIN® Injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN® Injection Premix in Single-Use Flexible Containers and LEVAQUIN® Injection in Single-Use Vials, or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of LEVAQUIN® Injection with an infusion solution compatible with LEVAQUIN® Injection and with any other drug(s) administered via this common line

LEVAQUIN® Injection in Single-Use Vials

Single-use vials require dilution prior to administration. 

LEVAQUIN® Injection is supplied in single-use vials containing a concentrated levofloxacin solution with the equivalent of 500 mg (20 mL vial) and 750 mg (30 mL vial) of levofloxacin in Water for Injection, USP. The 20 mL and 30 mL vials each contain 25 mg of levofloxacin/mL. These LEVAQUIN® Injection single-use vials must be further diluted with an appropriate solution prior to intravenous administration [see Table 4]. The concentration of the resulting diluted solution should be 5 mg/mL prior to administration.

Compatible Intravenous Solutions: Any of the following intravenous solutions may be used to prepare a 5 mg/mL levofloxacin solution with the approximate pH values:

Table 4: Compatible Intravenous Solutions Intravenous Fluids Final pH of LEVAQUIN® Solution 0.9% Sodium Chloride Injection, USP 4.71 5% Dextrose Injection, USP 4.58 5% Dextrose/0.9% NaCl Injection 4.62 5% Dextrose in Lactated Ringers 4.92 Plasma-Lyte® 56/5% Dextrose Injection 5.03 5% Dextrose, 0.45% Sodium Chloride, and 0.15% Potassium Chloride Injection 4.61 Sodium Lactate Injection (M/6) 5.54

Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final intravenous solution. Since the vials are for single-use only, any unused portion remaining in the vial should be discarded. When used to prepare two 250 mg doses from the 20 mL vial containing 500 mg of levofloxacin, the full content of the vial should be withdrawn at once using a single-entry procedure, and a second dose should be prepared and stored for subsequent use [see Stability of LEVAQUIN® Injection Following Dilution].

Prepare the desired dosage of levofloxacin according to Table 5:

Table 5: Preparation of LEVAQUIN® Intravenous Solution Desired Dosage Strength From Appropriate Vial,Withdraw Volume Volume of Diluent Infusion Time 250 mg 10 mL (20 mL Vial) 40 mL 60 min 500 mg 20 mL (20 mL Vial) 80 mL 60 min 750 mg 30 mL (30 mL Vial) 120 mL 90 min

For example, to prepare a 500 mg dose using the 20 mL vial (25 mg/mL), withdraw 20 mL and dilute with a compatible intravenous solution to a total volume of 100 mL.

This intravenous drug product should be inspected visually for particulate matter prior to administration. Samples containing visible particles should be discarded.

Stability of LEVAQUIN® Injection Following Dilution: LEVAQUIN® Injection, when diluted in a compatible intravenous fluid to a concentration of 5 mg/mL, is stable for 72 hours when stored at or below 25°C (77°F) and for 14 days when stored under refrigeration at 5°C (41°F) in plastic intravenous containers. Solutions that are diluted in a compatible intravenous solution and frozen in glass bottles or plastic intravenous containers are stable for 6 months when stored at - 20°C (- 4°F). Thaw frozen solutions at room temperature 25°C (77°F) or in a refrigerator 8°C (46°F). Do not force thaw by microwave irradiation or water bath immersion. Do not refreeze after initial thawing.

LEVAQUIN® Injection Premix in Single-Use Flexible Containers (5 mg/mL)

LEVAQUIN® Injection is also supplied in flexible containers within a foil overwrap. These contain a premixed, ready to use levofloxacin solution in 5% dextrose (D5W) for single-use. The 100 mL premixed flexible containers contain either 250 mg/50 mL or 500 mg/100 mL of levofloxacin solution. The 150 mL flexible container contains 750 mg/150 mL of levofloxacin solution. The concentration of each container is 5 mg/mL. No further dilution of these preparations is necessary. Because the premix flexible containers are for single-use only, any unused portion should be discarded.

Instructions for the Use of LEVAQUIN® Injection Premix in Flexible Containers:

Tear outer wrap at the notch and remove solution container. Check the container for minute leaks by squeezing the inner bag firmly. If leaks are found, or if the seal is not intact, discard the solution, as the sterility may be compromised. Do not use if the solution is cloudy or a precipitate is present. Use sterile equipment. WARNING: Do not use flexible containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for Administration:

Close flow control clamp of administration set. Remove cover from port at bottom of container. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton. Suspend container from hanger. Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of LEVAQUIN® Injection Premix in Flexible Containers. Open flow control clamp to expel air from set. Close clamp. Regulate rate of administration with flow control clamp.

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Myocardial Infarction

Early Treatment

During the early phase of definite or suspected acute myocardial infarction, treatment with metoprolol tartrate can be initiated 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.

Treatment in this early phase should begin with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; the injections should be given at approximately 2-minute intervals. During the intravenous administration of metoprolol tartrate, blood pressure, heart rate, and electrocardiogram should be carefully monitored.

In patients who tolerate the full intravenous dose (15 mg), metoprolol tartrate tablets, 50 mg every 6 hours, should be initiated 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, patients should receive a maintenance dosage of 100 mg twice daily (see Late Treatment below).

Patients who appear not to tolerate the full intravenous dose should be started 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, treatment with metoprolol tartrate should be discontinued (see WARNINGS).

Late Treatment

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 should be started on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Therapy should be continued for at least 3 months. Although the efficacy of metoprolol tartrate 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.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

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INFANTS

2 mL (200,000 units) four times daily (in infants and young children, use dropper to place one-half of dose in each side of mouth and avoid feeding for 5 to 10 minutes).

NOTE: Limited clinical studies in premature and low birth weight infants indicate that 1 mL four times daily is effective.

CHILDREN AND ADULTS

4-6 mL (400,000 to 600,000 units) four times daily (one-half of dose in each side of mouth). The preparation should be retained in the mouth as long as possible before swallowing.

Continue treatment for at least 48 hours after perioral symptoms have disappeared and cultures demonstrate eradication of Candida albicans.

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Norepinephrine bitartrate injection is a concentrated, potent drug which must be diluted in dextrose containing solutions prior to infusion. An infusion of norepinephrine should be given into a large vein. (See PRECAUTIONS.)

Restoration of Blood Pressure in Acute Hypotensive States

Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, norepinephrine can be administered before and concurrently with blood volume replacement.

Diluent

Norepinephrine should be diluted in 5 percent dextrose injection or 5 percent dextrose and sodium chloride injections. These dextrose containing fluids are protection against significant loss of potency due to oxidation. Administration in saline solution alone is not recommended. Whole blood or plasma, if indicated to increase blood volume, should be administered separately (for example, by use of a Y-tube and individual containers if given simultaneously).

Average Dosage

Add a 4 mL vial (4 mg) of norepinephrine to 1,000 mL of a 5 percent dextrose containing solution. Each mL of this dilution contains 4 mcg of the base of norepinephrine. Give this solution by intravenous infusion. Insert a plastic intravenous catheter through a suitable bore needle well advanced centrally into the vein and securely fixed with adhesive tape, avoiding, if possible, a catheter tie-in technique as this promotes stasis. An IV drip chamber or other suitable metering device is essential to permit an accurate estimation of the rate of flow in drops per minute. After observing the response to an initial dose of 2 mL to 3 mL (from 8 mcg to 12 mcg of base) per minute, adjust the rate of flow to establish and maintain a low normal blood pressure (usually 80 mm Hg to 100 mm Hg systolic) sufficient to maintain the circulation to vital organs. In previously hypertensive patients, it is recommended that the blood pressure should be raised no higher than 40 mm Hg below the preexisting systolic pressure. The average maintenance dose ranges from 0.5 mL to 1 mL per minute (from 2 mcg to 4 mcg of base).

High Dosage

Great individual variation occurs in the dose required to attain and maintain an adequate blood pressure. In all cases, dosage of norepinephrine should be titrated according to the response of the patient. Occasionally much larger or even enormous daily doses (as high as 68 mg base or 17 vials) may be necessary if the patient remains hypotensive, but occult blood volume depletion should always be suspected and corrected when present. Central venous pressure monitoring is usually helpful in detecting and treating this situation.

Fluid Intake

The degree of dilution depends on clinical fluid volume requirements. If large volumes of fluid (dextrose) are needed at a flow rate that would involve an excessive dose of the pressor agent per unit of time, a solution more dilute than 4 mcg per mL should be used. On the other hand, when large volumes of fluid are clinically undesirable, a concentration greater than 4 mcg per mL may be necessary.

Duration of Therapy

The infusion should be continued until adequate blood pressure and tissue perfusion are maintained without therapy. Infusions of norepinephrine should be reduced gradually, avoiding abrupt withdrawal. In some of the reported cases of vascular collapse due to acute myocardial infarction, treatment was required for up to six days.

Adjunctive Treatment in Cardiac Arrest

Infusions of norepinephrine are usually administered intravenously during cardiac resuscitation to restore and maintain an adequate blood pressure after an effective heartbeat and ventilation have been established by other means. [Norepinephrine's powerful beta-adrenergic stimulating action is also thought to increase the strength and effectiveness of systolic contractions once they occur.]

Average Dosage

To maintain systemic blood pressure during the management of cardiac arrest, norepinephrine is used in the same manner as described under Restoration of Blood Pressure in Acute Hypotensive States.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use, whenever solution and container permit.

Do not use the solution if its color is pinkish or darker than slightly yellow or if it contains a precipitate.

Avoid contact with iron salts, alkalis, or oxidizing agents.

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Note: Cefazolin for Injection in the ADD-Vantage® Vial is not intended for direct intravenous injection.

Usual Adult Dosage

* In rare instances, doses of up to 12 grams of Cefazolin for Injection per day have been used. Type of Infection Dose Frequency Moderate to severe infections 500 mg to 1 gram every 6 to 8 hrs. Mild infections caused by susceptible 250 mg to 500 mg every 8 hours gram-positive cocci Acute, uncomplicated urinary 1 gram every 12 hours tract infections Pneumococcal pneumonia 500 mg every 12 hours Severe, life-threatening infections 1 gram to 1.5 grams every 6 hours (e.g., endocarditis, septicemia)*

Perioperative Prophylactic Use

To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are:

a. 1 gram I.V. administered 1/2 hour to 1 hour prior to the start of surgery.

b. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram I.V. during surgery (administration modified depending on the duration of the operative procedure).

c. 500 mg to 1 gram I.V. every 6 to 8 hours for 24 hours postoperatively.

It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior to the start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision; and (2) Cefazolin for Injection be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms.

In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of Cefazolin for Injection may be continued for 3 to 5 days following the completion of surgery.

Dosage Adjustment for Patients with Reduced Renal Function

Cefazolin for Injection may be used in patients with reduced renal function with the following dosage adjustments: Patients with a creatinine clearance of 55 mL/min. or greater or a serum creatinine of 1.5 mg% or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3 mg% can also be given full doses but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine of 3.1 to 4.5 mg% should be given 1/2 the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min. or less or serum creatinine of 4.6 mg% or greater should be given 1/2 the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. Patients undergoing peritoneal dialysis: See CLINICAL PHARMACOLOGY.

Pediatric Dosage

In pediatric patients, a total daily dosage of 25 to 50 mg per kg (approximately 10 to 20 mg per pound) of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections. Total daily dosage may be increased to 100 mg per kg (45 mg per pound) of body weight for severe infections. Since safety for use in premature infants and in neonates has not been established, the use of Cefazolin for Injection in these patients is not recommended.

Pediatric Dosage Guide Weight

25 mg/kg/day

Divided into 3 Doses

25 mg/kg/day

Divided into 4 Doses

Lbs Kg Approximate Single Dose mg/q8h Vol. (mL) needed with dilution of 125 mg/mL Approximate Single Dose mg/q6h Vol. (mL) needed with dilution of 125 mg/mL 10 4.5 40 mg 0.35 mL 30 mg 0.25 mL 20 9 75 mg 0.6 mL 55 mg 0.45 mL 30 13.6 115 mg 0.9 mL 85 mg 0.7 mL 40 18.1 150 mg 1.2 mL 115 mg 0.9 mL 50 22.7 190 mg 1.5 mL 140 mg 1.1 mL Weight

50 mg/kg/day

Divided into 3 Doses

50 mg/kg/day

Divided into 4 Doses

Lbs Kg Approximate Single Dose mg/q8h Vol. (mL) needed with dilution of 225 mg/mL Approximate Single Dose mg/q6h Vol. (mL) needed with dilution of 225 mg/mL 10 4.5 75 mg 0.35 mL 55 mg 0.25 mL 20 9 150 mg 0.7 mL 110 mg 0.5 mL 30 13.6 225 mg 1 mL 170 mg 0.75 mL 40 18.1 300 mg 1.35 mL 225 mg 1 mL 50 22.7 375 mg 1.7 mL 285 mg 1.25 mL

In pediatric patients with mild to moderate renal impairment (creatinine clearance of 70 to 40 mL/min.), 60 percent of the normal daily dose given in equally divided doses every 12 hours should be sufficient. In patients with moderate impairment creatinine clearance of 40 to 20 mL/min.), 25 percent of the normal daily dose given in equally divided doses every 12 hours should be adequate. Pediatric patients with severe renal impairment (creatinine clearance of 20 to 5 mL/min.) may be given 10 percent of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose.

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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.

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Usual Adult Dosage

* In rare instances, doses of up to 12 grams of Cefazolin for Injection per day have been used. Type of Infection Dose Frequency Moderate to severe infections 500 mg to 1 gram every 6 to 8 hrs. Mild infections caused by susceptible gram-positive cocci

250 mg to 500 mg

every 8 hours

Acute, uncomplicated urinary tract infections 1 gram every 12 hours Pneumococcal pneumonia 500 mg every 12 hours Severe, life-threatening infections (e.g., endocarditis, septicemia)*

1 gram to 1.5 grams

every 6 hours

Perioperative Prophylactic Use

To prevent postoperative infection in contaminated or potentially contaminated surgery, the recommended doses are:

a. 1 gram IV or IM administered 1/2 hour to 1 hour prior to the start of surgery.

b. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV or IM during surgery (administration modified depending on the duration of the operative procedure).

c. 500 mg to 1 gram IV or IM every 6 to 8 hours for 24 hours postoperatively.

It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior to the start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision; and (2) Cefazolin for Injection be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms.

In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of Cefazolin for Injection may be continued for 3 to 5 days following the completion of surgery.

Dosage Adjustment for Patients with Reduced Renal Function

Cefazolin for Injection may be used in patients with reduced renal function with the following dosage adjustments: Patients with a creatinine clearance of 55 mL/min. or greater or a serum creatinine of 1.5 mg% or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3 mg% can also be given full doses but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine of 3.1 to 4.5 mg% should be given 1/2 the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min. or less or serum creatinine of 4.6 mg% or greater should be given 1/2 the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. Patients undergoing peritoneal dialysis: see CLINICAL PHARMACOLOGY.

Pediatric Dosage

In pediatric patients, a total daily dosage of 25 to 50 mg per kg (approximately 10 to 20 mg per pound) of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections. Total daily dosage may be increased to 100 mg per kg (45 mg per pound) of body weight for severe infections. Since safety for use in premature infants and in neonates has not been established, the use of Cefazolin for Injection in these patients is not recommended.

Pediatric Dosage Guide Weight

25 mg/kg/day

Divided into 3 Doses

25 mg/kg/day

Divided into 4 Doses lbs kg

Approximate

Single Dose

(mg/q8 h)

Vol. (mL)

Needed with

Dilution of

125 mg/mL

Approximate

Single Dose

(mg/q6 h)

Vol. (mL)

Needed with

Dilution of

125 mg/mL 10 4.5 40 mg 0.35 mL 30 mg 0.25 mL 20 9 75 mg 0.6 mL 55 mg 0.45 mL 30 13.6 115 mg 0.9 mL 85 mg 0.7 mL 40 18.1 150 mg 1.2 mL 115 mg 0.9 mL 50 22.7 190 mg 1.5 mL 140 mg 1.1 mL Weight

50 mg/kg/day

Divided into 3 Doses

50 mg/kg/day

Divided into 4 Doses lbs kg

Approximate

Single Dose

(mg/q8 h)

Vol. (mL)

Needed with

Dilution of

225 mg/mL

Approximate

Single Dose

(mg/q6 h)

Vol. (mL)

Needed with

Dilution of

225 mg/mL 10 4.5 75 mg 0.35 mL 55 mg 0.25 mL 20 9 150 mg 0.7 mL 110 mg 0.5 mL 30 13.6 225 mg 1 mL 170 mg 0.75 mL 40 18.1 300 mg 1.35 mL 225 mg 1 mL 50 22.7 375 mg 1.7 mL 285 mg 1.25 mL

In pediatric patients with mild to moderate renal impairment (creatinine clearance of 70 to 40 mL/min.), 60 percent of the normal daily dose given in equally divided doses every 12 hours should be sufficient. In patients with moderate impairment (creatinine clearance of 40 to 20 mL/min.), 25 percent of the normal daily dose given in equally divided doses every 12 hours should be adequate. Pediatric patients with severe renal impairment (creatinine clearance of 20 to 5 mL/min.) may be given 10 percent of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose.

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

Valproic Acid Capsules, USP is administered orally. Valproic Acid Capsules, USP is 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 has 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 Total Daily Dose (mg) Number of Capsules (Kg) (Lb) 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 Patient - 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.

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Do not take more than directed

Adults and Children 12 years and over: ■ Take 2 caplets every 4 to 6 hours while symptoms last

■ Do not take more than 8 caplets in 24 hours ■ Do not take for more than 10 days unless

directed by a doctor

Children under 12 years: Do not use adult Extra Strength product in children under 12 years of

age; this will provide more than the recommended dose (overdose) of acetaminophen and may

cause liver damage.

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Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.

Parenteral routes of administration other than intravenous are not recommended.

PROTONIX I.V. for Injection may be administered intravenously through a dedicated line or through a Y-site. The intravenous line should be flushed before and after administration of PROTONIX I.V. for Injection with either 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP. When administered through a Y-site, PROTONIX I.V. for Injection is compatible with the following solutions: 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP.

Midazolam HCl has been shown to be incompatible with Y-site administration of PROTONIX I.V. for Injection. PROTONIX I.V. for Injection may not be compatible with products containing zinc. When PROTONIX I.V. for Injection is administered through a Y-site, immediately stop use if precipitation or discoloration occurs.

2.1 Gastroesophageal Reflux Disease Associated With a History of Erosive Esophagitis

Recommended Dosage

The recommended adult dose is 40 mg pantoprazole given once daily by intravenous infusion for 7 to 10 days.

Treatment with PROTONIX® I.V. (pantoprazole sodium) for Injection should be discontinued as soon as the patient is able to receive treatment with PROTONIX Delayed-Release Tablets or Oral Suspension.

Administration and Preparation Instructions

Data on the safe and effective dosing for conditions other than those described [see Indications and Usage (1)] such as life-threatening upper gastrointestinal bleeds, are not available. PROTONIX I.V. 40 mg once daily does not raise gastric pH to levels sufficient to contribute to the treatment of such life-threatening conditions.

Fifteen Minute Infusion

PROTONIX I.V. for Injection should be reconstituted with 10 mL of 0.9% Sodium Chloride Injection, USP, and further diluted (admixed) with 100 mL of 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP, to a final concentration of approximately 0.4 mg/mL. The reconstituted solution may be stored for up to 6 hours at room temperature prior to further dilution. The admixed solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution. Both the reconstituted solution and the admixed solution do not need to be protected from light.

PROTONIX I.V. for Injection admixtures should be administered intravenously over a period of approximately 15 minutes at a rate of approximately 7 mL/min.

Two Minute Infusion

PROTONIX I.V. for Injection should be reconstituted with 10 mL of 0.9% Sodium Chloride Injection, USP, to a final concentration of approximately 4 mg/mL. The reconstituted solution may be stored for up to 24 hours at room temperature prior to intravenous infusion and does not need to be protected from light. PROTONIX I.V. for Injection should be administered intravenously over a period of at least 2 minutes.

2.2 Pathological Hypersecretion Including Zollinger-Ellison Syndrome

Recommended Dosage

The dosage of PROTONIX I.V. for Injection in patients with pathological hypersecretory conditions including Zollinger-Ellison Syndrome varies with individual patients. The recommended adult dosage is 80 mg intravenously every 12 hours. The frequency of dosing can be adjusted to individual patient needs based on acid output measurements. In those patients who need a higher dosage, 80 mg intravenously every 8 hours is expected to maintain acid output below 10 mEq/h. Daily doses higher than 240 mg or administered for more than 6 days have not been studied [see Clinical Studies (14)]. Transition from oral to intravenous and from intravenous to oral formulations of gastric acid inhibitors should be performed in such a manner to ensure continuity of effect of suppression of acid secretion. Patients with Zollinger-Ellison Syndrome may be vulnerable to serious clinical complications of increased acid production even after a short period of loss of effective inhibition.

Administration and Preparation Instructions

Fifteen Minute Infusion

Each vial of PROTONIX I.V. for Injection should be reconstituted with 10 mL of 0.9% Sodium Chloride Injection, USP. The contents of the two vials should be combined and further diluted (admixed) with 80 mL of 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP, to a total volume of 100 mL with a final concentration of approximately 0.8 mg/mL. The reconstituted solution may be stored for up to 6 hours at room temperature prior to further dilution. The admixed solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution. Both the reconstituted solution and the admixed solution do not need to be protected from light.

PROTONIX I.V. for Injection should be administered intravenously over a period of approximately 15 minutes at a rate of approximately 7 mL/min.

Two minute Infusion

PROTONIX I.V. for Injection should be reconstituted with 10 mL of 0.9% Sodium Chloride Injection, USP, per vial to a final concentration of approximately 4 mg/mL. The reconstituted solution may be stored for up to 24 hours at room temperature prior to intravenous infusion and does not need to be protected from light. The total volume from both vials should be administered intravenously over a period of at least 2 minutes.

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do not take more than directed (see Liver warning) adults and children 12 years and over take 2 caplets every 4 hours do not take more than 12 caplets in 24 hours swallow whole – do not crush, chew or dissolve children under 12 years do not use this adult product in children under 12 years of age

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adults and children 12 years and over take 2 tablets every 4 to 6 hours do not take more than 8 tablets in 24 hours children ages 6 to 12 years take 1 tablet every 4 to 6 hours do not take more than 4 tablets in 24 hours children under 6 years do not use this product in children under 6 years of age

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Prevention of Chemotherapy-Induced Nausea and Vomiting

Adult Dosing

The recommended IV dosage of ondansetron for adults is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. The recommended infusion rate should not be exceeded (see OVERDOSAGE). With the three-dose (0.15 mg/kg) regimen, the first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of ondansetron.

Ondansetron Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.

Vial

DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Pediatric Dosing

On the basis of the available information (see CLINICAL TRIALS, Pediatric Studies and CLINICAL PHARMACOLOGY, Pharmacokinetics), the dosage in pediatric cancer patients 6 months to 18 years of age should be three 0.15 mg/kg doses. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy, subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of ondansetron. The drug should be infused intravenously over 15 minutes. Little information is available about dosage in pediatric cancer patients younger than 6 months of age.

Vial

DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Geriatric Dosing

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

Prevention of Postoperative Nausea and Vomiting

Adult Dosing

The recommended IV dosage of ondansetron for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, IV dose of ondansetron 4 mg, administration of a second IV dose of 4 mg ondansetron postoperatively does not provide additional control of nausea and vomiting.

Vial

REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

Pediatric Dosing

The recommended IV dosage of ondansetron for pediatric surgical patients (1 month to 12 years of age) is a single 0.1 mg/kg dose for patients weighing 40 kg or less, or a single 4 mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic ondansetron.

Vial

REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.

Geriatric Dosing

The dosage recommendation 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), a single maximal daily dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron.

Stability

Ondansetron Injection is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following IV fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 3% Sodium Chloride Injection.

Although Ondansetron Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative. After dilution, do not use beyond 24 hours.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Precaution

Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.

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• do not take more than 6 doses in any 24-hour period • measure only with dosing cup provided • keep dosing cup with product • mL = milliliter • this adult product is not intended for use in children under 12 years of age

age

dose

adults and children 12 years and over

10 mL every 4 hours

children under 12 years

do not use