Boca Pharmacal, Llc

---

Methimazole is administered orally. It is usually given in 3 equal doses at approximately 8-hour intervals.

Adults

The initial daily dosage is 15 mg for mild hyperthyroidism, 30 to 40 mg for moderately severe hyperthyroidism, and 60 mg for severe hyperthyroidism, divided into 3 doses at 8-hour intervals. The maintenance dosage is 5 to 15 mg daily.

Pediatric

Initially, the daily dosage is 0.4 mg/kg of body weight divided into 3 doses and given at 8-hour intervals. The maintenance dosage is approximately 1/2 of the initial dose.

---

2.1  Important Administration Instructions

Levetiracetam is given orally with or without food. The levetiracetam dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.

Prescribe the oral solution for pediatric patients with body weight ≤ 20 kg. Prescribe the oral solution or tablets for pediatric patients with body weight above 20 kg.

When using the oral solution in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).

Levetiracetam tablets, USP should be swallowed whole. Levetiracetam tablets, USP should not be chewed or crushed.

2.2  Dosing for Partial Onset Seizures

Adults 16 Years And Older

Initiate treatment with a daily dose of 1,000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1,000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3,000 mg. There is no evidence that doses greater than 3,000 mg/day confer additional benefit.

Pediatric Patients

Information describing the use of levetiracetam tablets in pediatric patients less than 4 years of age as adjunctive therapy in the treatment of partial onset seizures is approved for UCB, Inc.’s levetiracetam tablets. However, due to UCB Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

4 Years To < 16 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3,000 mg/day.

For Levetiracetam tablets, USP dosing in pediatric patients weighing 20 to 40 kg, initiate treatment with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). Increase the daily dose every 2 weeks by increments of 500 mg to a maximum recommended daily dose of 1,500 mg (750 mg twice daily).

For Levetiracetam tablets, USP dosing in pediatric patients weighing more than 40 kg, initiate treatment with a daily dose of 1,000 mg/day given as twice daily dosing (500 mg twice daily). Increase the daily dose every 2 weeks by increments of 1,000 mg/day to a maximum recommended daily dose of 3,000 mg (1,500 mg twice daily).

Levetiracetam Oral Solution Weight-Based Dosing Calculation For Pediatric PatientsThe following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients:

2.3  Dosing for Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy

Initiate treatment with a dose of 1,000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase the dosage by 1,000 mg/day every 2 weeks to the recommended daily dose of 3,000 mg. The effectiveness of doses lower than 3,000 mg/day has not been studied.

2.4  Dosing for Primary Generalized Tonic-Clonic Seizures

Adults 16 Years And Older

Initiate treatment with a dose of 1,000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase dosage by 1,000 mg/day every 2 weeks to the recommended daily dose of 3,000 mg. The effectiveness of doses lower than 3,000 mg/day has not been adequately studied.

Pediatric Patients Ages 6 To <16 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution [see Dosage and Administration (2.1)]. Only whole tablets should be administered.

2.5  Dosage Adjustments in Adult Patients with Renal Impairment

Levetiracetam dosing must be individualized according to the patient’s renal function status. Recommended dosage adjustments for adults are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this an estimate of the patient’s creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:

Then CLcr is adjusted for body surface area (BSA) as follows:

Table 1: Dosing Adjustment Regimen For Adult Patients With Renal Impairment  Group

Creatinine Clearance

(mL/min/1.73m2)  Dosage (mg)  Frequency Normal > 80 500 to 1,500 Every 12 hours Mild 50 – 80 500 to 1,000 Every 12 hours Moderate 30 – 50 250 to 750 Every 12 hours Severe < 30 250 to 500 Every 12 hours ESRD patients using dialysis - - - - 500 to 1,0001 Every 24 hours1

1 Following dialysis, a 250 to 500 mg supplemental dose is recommended.

---

Acute otitis media: Instill Antipyrine and Benzocaine Otic Solution, permitting the solution to run along the wall of the ear canal until it is filled. Avoid touching the ear with dropper. Then moisten a cotton pledget with Antipyrine and Benzocaine Otic Solution and insert into meatus. Repeat every one to two hours until pain and congestion are relieved.

Removal of Cerumen:

Before: Instill Antipyrine and Benzocaine Otic Solution three times daily for two or three days to help detach cerumen from wall of ear canal and facilitate removal.

After: Antipyrine and Benzocaine Otic Solution is useful for drying out the ear canal or relieving discomfort.

Before and after removal of cerumen, a cotton pledget moistened with Antipyrine and Benzocaine Otic Solution should be inserted into the meatus following instillation.

---

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

Anxiety Disorders and Transient Symptoms of Anxiety

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

In all patients, dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage. Although there are no systematically collected data to support a specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more than 0.5 mg every 3 days. Some patients may require an even slower dosage reduction.

Panic Disorder

The successful treatment of many panic disorder patients has required the use of alprazolam at doses greater than 4 mg daily. In controlled trials conducted to establish the efficacy of alprazolam in panic disorder, doses in the range of 1 to 10 mg daily were used. The mean dosage employed was approximately 5 to 6 mg daily. Among the approximately 1700 patients participating in the panic disorder development program, about 300 received alprazolam in dosages of greater than 7 mg/day, including approximately 100 patients who received maximum dosages of greater than 9 mg/day. Occasional patients required as much as 10 mg a day to achieve a successful response.

Dose Titration

Treatment may be initiated with a dose of 0.5 mg three times daily. Depending on the response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg per day. Slower titration to the dose levels greater than 4 mg/day may be advisable to allow full expression of the pharmacodynamic effect of alprazolam. To lessen the possibility of interdose symptoms, the times of administration should be distributed as evenly as possible throughout the waking hours, that is, on a three or four times per day schedule.

Generally, therapy should be initiated at a low dose to minimize the risk of adverse responses in patients especially sensitive to the drug. Dose should be advanced until an acceptable therapeutic response (i.e., a substantial reduction in or total elimination of panic attacks) is achieved, intolerance occurs, or the maximum recommended dose is attained.

Dose Maintenance

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

The necessary duration of treatment for panic disorder patients responding to alprazolam is unknown. After a period of extended freedom from attacks, a carefully supervised tapered discontinuation may be attempted, but there is evidence that this may often be difficult to accomplish without recurrence of symptoms and/or the manifestation of withdrawal phenomena.

Dose Reduction

Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided (see WARNINGS, PRECAUTIONS, DRUG ABUSE AND DEPENDENCE).

In all patients, dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage. Although there are no systematically collected data to support a specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.

In any case, reduction of dose must be undertaken under close supervision and must be gradual. If significant withdrawal symptoms develop, the previous dosing schedule should be reinstituted and, only after stabilization, should a less rapid schedule of discontinuation be attempted. In a controlled postmarketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. It is suggested that the dose be reduced by no more than 0.5 mg every 3 days, with the understanding that some patients may benefit from an even more gradual discontinuation. Some patients may prove resistant to all discontinuation regimens.

Dosing in Special Populations

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

---

Dosage should be individualized according to the response of the patient. The suggested dosage ranges from 25 to 50 mg one to three times daily.  Treatment should begin with 25 to 50 mg once daily with subsequent increase in individual dose or frequency according to response. A single daily dose is preferably given in mid-morning or mid-afternoon, according to the patient’s eating habits. In an occasional patient it may be desirable to avoid late afternoon administration. Use of benzphetamine hydrochloride is not recommended in individuals under 12 years of age.

---

The average dosage of Methscopolamine Bromide Tablets USP is 2.5 mg one-half hour before meals and 2.5 to 5 mg at bedtime. A starting dose of 12.5 mg daily will be clinically effective in most patients without the production of appreciable side effects.

If the patient is having severe symptoms which demand prompt relief, the drug may be started on a daily dosage of 20 mg, administered in doses of 5 mg one-half hour before meals and at bedtime. If very unpleasant side effects develop promptly, the daily dosage should be reduced. If neither symptomatic relief nor side effects appear, the daily dosage may be increased. Some patients have tolerated 30 mg daily with no unpleasant reactions.

Patients whose dosage has been reduced to eliminate or modify side effects often continue to show adequate response both subjectively in relief of symptoms and objectively as measured by antisecretory effects.

The ultimate aim of therapy is to arrive at a dosage which provides maximal clinical effectiveness with a minimum of unpleasant side effects. Many patients report no side effects on a dosage which gives complete relief of symptoms. On the other hand, some patients have reported severe side effects without appreciable symptomatic relief. Such patients must be considered unsuited for this therapy. Usually they have been or will prove to be similarly intolerant to other anticholinergic drugs. If methscopolamine bromide is to be used in a patient who gives a history of such intolerance, it should be

started at a low dosage.

---

Carbinoxamine maleate is contraindicated in children younger than 2 years of age (see CONTRAINDICATIONS).

Carbinoxamine maleate should be taken on an empty stomach with water.

DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT.

Carbinoxamine maleate dosage should be based on the severity of the condition and the response of the patient. The drug is well tolerated in adult doses as high as 24 mg daily, in divided doses, over prolonged periods. On the other hand, some patients respond to as little as 4 mg daily.

Clinical experience suggests the following dosage schedules:

Tablets

Usual Adult Dosage:

1 or 2 tablets (4 to 8 mg) 3 to 4 times daily.

Usual Child’s Dosage:

Six to eleven years – 1/2 to 1 tablet (2 to 4 mg) 3 to 4 times daily.

Oral Solution

Usual Adult Dosage:

1 or 2 teaspoonfuls (4 to 8 mg) 3 to 4 times daily.

Usual Child’s Dosage:

(approximately 0.2 to 0.4 mg/kg/day, divided into 3 to 4 doses):

Six to eleven years – 1/2 to 1 teaspoonful (2 to 4 mg) 3 to 4 times daily.

Dosing for children 2 to 5 years of age should be based on weight whenever possible. The usual dosage for children 2 to 5 years of age is approximately 0.2 to 0.4 mg/kg/day, divided into 3 to 4 daily doses. In general, this corresponds to a dose of 1/4 to 1/2 teaspoonful (1 to 2 mg) 3 to 4 times daily.

---

Levetiracetam is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

Partial Onset Seizures

Adults 16 Years And Older

In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients Ages 4 To <16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 10 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

Levetiracetam is given orally with or without food.

The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or 60 mg/kg/day:

A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.

Adult Patients With Impaired Renal Function

Levetiracetam dosing must be individualized according to the patient’s renal function status. Recommended doses and adjustment for dose for adults are shown in Table 11. To use this dosing table, an estimate of the patient’s creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:

---

See following chart. May be dropped directly into mouth with dropper; or mixed with cereal, fruit juice or other food.

---

See following chart. May be dropped directly into mouth with dropper; or mixed with cereal, fruit juice or other food.

---

See following chart. May be dropped directly into mouth with dropper; or mixed with cereal, fruit juice or other food.

---

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

2.1    Recommended Adults Dosage

The recommended adult dosage is based on body weight as follows:

•    For patients weighing less than 60 kg: 30 mg every 12 hours.

•    For patients weighing at least 60 kg: 40 mg every 12 hours.

2.2    Recommended Pediatric Dosage

•    For newborns from birth to 13 days old: 0.5 mg/kg given every 12 hours.

•    For pediatric patients at least 14 days old and weighing less than 30 kg: 1 mg/kg given every 12 hours.

•    For pediatric patients weighing at least 30 kg: use the recommended adult dosage.

2.3    Dosage Adjustment

Renal Impairment Adult Patients: Stavudine may be administered to adult patients with impaired renal function with an adjustment in dosage as shown in Table 1.

Table 1: Recommended Dosage Adjustment for Adult Patients with Renal Impairment Creatinine Clearance(mL/min) Recommended Stavudine Dose by Patient Weight At least 60 kg Less than 60 kg * Administered after the completion of hemodialysis on dialysis days and at the same time of day on non-dialysis days. greater than 50 40 mg every 12 hours 30 mg every 12 hours 26-50 20 mg every 12 hours 15 mg every 12 hours 10-25 20 mg every 24 hours 15 mg every 24 hours Hemodialysis 20 mg every 24 hours* 15 mg every 24 hours*

Pediatric Patients: Since urinary excretion is also a major route of elimination of stavudine in pediatric patients, the clearance of stavudine may be altered in children with renal impairment. There are insufficient data to recommend a specific dose adjustment of stavudine in this patient population.

2.4    Method of Preparation for Oral Solution

Prior to dispensing, the pharmacist must constitute the dry powder with purified water to a concentration of 1 mg stavudine per mL of solution, as follows:

1.  Add 200 mL of purified water to the container.

2.  Shake container vigorously until the powder dissolves completely. Constitution in this way produces 200 mL (deliverable volume) of 1 mg/mL stavudine solution. The solution may appear slightly hazy.

3.  Dispense solution in original container with measuring cup provided. Instruct patient to shake the container vigorously prior to measuring each dose and to store the tightly closed container in a refrigerator, 2°C to 8°C (36°F to 46°F). Discard any unused portion after 30 days.

---

2.1    Treatment of HIV-1 Infection

Adults: The recommended oral dose of zidovudine is 600 mg/day in divided doses in combination with other antiretroviral agents.

Pediatric Patients (Aged 4 Weeks to <18 Years): Healthcare professionals should pay special attention to accurate calculation of the dose of Zidovudine, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.

Prescribers should calculate the appropriate dose of zidovudine for each child based on body weight (kg) and should not exceed the recommended adult dose.

Before prescribing Zidovudine capsules, children should be assessed for the ability to swallow capsules. If a child is unable to reliably swallow a Zidovudine capsule, the Zidovudine syrup formulation should be prescribed.

The recommended dosage in pediatric patients 4 weeks of age and older and weighing ≥4 kg is provided in Table 1. Zidovudine syrup should be used to provide accurate dosage when whole tablets or capsules are not appropriate.

Table 1: Recommended Pediatric Dosage of Zidovudine

Body Weight (kg) Total Daily Dose Dosage Regimen and Dose Twice Daily Three Times Daily 4 to <9 24 mg/kg/day 12 mg/kg 8 mg/kg ≥ 9 to <30 18 mg/kg/day 9 mg/kg 6 mg/kg ≥ 30 600 mg/day 300 mg 200 mg

Alternatively, dosing for zidovudine can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine is 480 mg/m2/day in divided doses (240 mg/m2 twice daily or 160 mg/m2 three times daily). In some cases the dose calculated by mg/kg will not be the same as that calculated by BSA.

2.2    Prevention of Maternal-Fetal HIV-1 Transmission

The recommended dosage regimen for administration to pregnant women (>14 weeks of pregnancy) and their neonates is:

Maternal Dosing: 100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous zidovudine should be administered at 2 mg/kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg/kg/hour (total body weight) until clamping of the umbilical cord.

Neonatal Dosing: Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously. See Table 2.

Table 2. Recommended Neonatal Dosages of Zidovudine

Route Total Daily Dose Dose and Dosage Regimen Oral 8 mg/kg/day 2 mg/kg every 6 hours IV 6 mg/kg/day 1.5 mg/kg infused over 30 minutes, every 6 hours

2.3    Patients With Severe Anemia and/or Neutropenia

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

2.4    Patients With Renal Impairment

End-Stage Renal Disease: In patients maintained on hemodialysis or peritoneal dialysis, the recommended dosage is 100 mg every 6 to 8 hours [see Clinical Pharmacology (12.3)].

2.5    Patients With Hepatic Impairment

There are insufficient data to recommend dose adjustment of zidovudine in patients with mild to moderate impaired hepatic function or liver cirrhosis.

---

2.1    Treatment of HIV-1 Infection

Adults: The recommended oral dose of zidovudine is 600 mg/day in divided doses in combination with other antiretroviral agents.

Pediatric Patients (Aged 4 Weeks to <18 Years): Healthcare professionals should pay special attention to accurate calculation of the dose of Zidovudine, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.

Prescribers should calculate the appropriate dose of zidovudine for each child based on body weight (kg) and should not exceed the recommended adult dose.

Before prescribing Zidovudine Capsules or Tablets, children should be assessed for the ability to swallow capsules or tablets. If a child is unable to reliably swallow a Zidovudine Capsule or Tablet, the Zidovudine oral solution formulation should be prescribed.

The recommended dosage in pediatric patients 4 weeks of age and older and weighing ≥4 kg is provided in Table 1. Zidovudine oral solution should be used to provide accurate dosage when whole tablets or capsules are not appropriate.

Table 1: Recommended Pediatric Dosage of Zidovudine

Body Weight (kg) Total Daily Dose Dosage Regimen and Dose Twice Daily Three Times Daily 4 to <9 24 mg/kg/day 12 mg/kg 8 mg/kg ≥ 9 to <30 18 mg/kg/day 9 mg/kg 6 mg/kg ≥ 30 600 mg/day 300 mg 200 mg

Alternatively, dosing for zidovudine can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine is 480 mg/m2/day in divided doses (240 mg/m2 twice daily or 160 mg/m2 three times daily). In some cases the dose calculated by mg/kg will not be the same as that calculated by BSA.

2.2    Prevention of Maternal-Fetal HIV-1 Transmission

The recommended dosage regimen for administration to pregnant women (>14 weeks of pregnancy) and their neonates is:

Maternal Dosing: 100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous zidovudine should be administered at 2 mg/kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg/kg/hour (total body weight) until clamping of the umbilical cord.

Neonatal Dosing: Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously. See Table 2.

Table 2. Recommended Neonatal Dosages of Zidovudine

Route Total Daily Dose Dose and Dosage Regimen Oral 8 mg/kg/day 2 mg/kg every 6 hours IV 6 mg/kg/day 1.5 mg/kg infused over 30 minutes, every 6 hours

2.3    Patients With Severe Anemia and/or Neutropenia

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

2.4    Patients With Renal Impairment

End-Stage Renal Disease: In patients maintained on hemodialysis or peritoneal dialysis, the recommended dosage is 100 mg every 6 to 8 hours [see Clinical Pharmacology (12.3)].

2.5    Patients With Hepatic Impairment

There are insufficient data to recommend dose adjustment of zidovudine in patients with mild to moderate impaired hepatic function or liver cirrhosis.

---

See following chart. May be dropped directly into mouth with dropper; or mixed with cereal, fruit juice or other food.

Fluoride Ion Level in Drinking Water (ppm)*

Age

<0.3 ppm

0.3-0.6 ppm

>0.6 ppm

Birth - 6 months

None

None

None

6 mos - 3 years

0.25 mg (1 mL) / day**

None

None

3 - 6 years

0.50 mg (2 mL) / day

0.25 mg (1 mL) / day

None

*1.0 ppm = 1 mg/liter  ** 2.2 mg sodium fluoride contains 1 mg fluoride ion.

---

Dosage should be adjusted according to 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 tablespoonful every 4 to 6 hours as needed for pain. The total daily dosage for adults should not exceed 6 tablespoonfuls.

The usual dosages for children are given by the table on the next page, and are to be given every 4 to 6 hours as needed for pain. These dosages correspond to an average individual dose of 0.27 mL/kg of hydrocodone bitartrate and acetaminophen oral solution (providing 0.135 mg/kg of hydrocodone bitartrate and 5.85 mg/kg of acetaminophen). Dosing should be based on the weight whenever possible.

The total daily dosage for children should not exceed 6 doses per day.

It is of utmost importance that the dose of hydrocodone bitartrate and acetaminophen oral solution be administered accurately. A household teaspoon or tablespoon is not an adequate measuring device, especially when one-half or three-fourths of a teaspoonful is to be measured. Given the inexactitude of the household spoon measure and the possibility of using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that caregivers obtain and use a calibrated measuring device. Health care providers should recommend a dropper that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage.

---

Adults and pediatric patients 12 years of age and over: 10 mL (2 teaspoonfuls) every 4 hours. Children 6 to under 12 years of age: 5 mL (1 teaspoonful) every 4 hours.  Children 2 to under 6 years of age: 2.5 mL (½ teaspoonful) every 4 hours. Infants 6 months to under 2 years of age: Dosage to be established by a physician.

Do not exceed 6 doses during a 24-hour period.

---

2.1    Dosage in Adult Patients with Normal Renal Function

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

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].

 Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min)  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 isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)].  § Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)].  ¶ This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia.  # This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli.  Þ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9 )].

ß The safety of levofloxacin in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.

à Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Higher doses of levofloxacin typically used for treatm

 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 Þ, ß  Pediatric patients < 50 kg and ≥ 6 months of age Þ, ß  500 mgsee  Table 2 below (2.2) 

60ß 

60ß 

Plague, adult and pediatric patients > 50 kg à Pediatric patients < 50 kg and ≥ 6 months of age

500 mg

see Table 2 below (2.2)

10 to 14

10 to 14

2.2    Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.

  Table 2: Dosage in Pediatric Patients ≥ 6 months of age  Type of Infection*  Dose  Freq. Once every  Duration†  * Due to Bacillus anthracis [see Indications and Usage (1.13)] and Yersinia pestis [see Indications and Usage (1.14)].  † Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.  ‡ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)]

§ The safety of levofloxacin in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.

¶Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis.<</html>

 Inhalational Anthrax (post-exposure)‡,§  Pediatric patients > 50 kg  500 mg  24 hr  60 days§ Pediatric patients < 50 kg and ≥ 6  months of age

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

 

12 hr

 

60 days§

 

Plague¶

      Pediatric patients > 50 kg

500 mg

 

24 hr

 

10 to 14 days

   Pediatric patients < 50 kg and ≥ 6 months of age  8 mg/kg (not to exceed 250 mg per dose)  12 hr 10 to 14 days 

2.3    Dosage Adjustment in Adults with Renal Impairment

Administer levofloxacin with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance <50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations (8.6)].

Table 3 shows how to adjust dose based on creatinine clearance.

  Table 3: Dosage Adjustment in Adult Patients with Renal Impairment (creatinine clearance <50 mL/min)   Dosage in Normal Renal Function Every 24 hours   Creatinine Clearance 20 to 49 mL/min   Creatinine Clearance 10 to 19 mL/min   Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD)  750 mg  750 mg every 48 hours  750 mg initial dose, then 500 mg every 48 hours  750 mg initial dose, then 500 mg every 48 hours  500 mg  500 mg initial dose, then 250 mg every 24 hours  500 mg initial dose, then 250 mg every 48 hours  500 mg initial dose, then 250 mg every 48 hours  250 mg  No dosage adjustment required  250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required  No information on dosing adjustment is available

2.4    Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

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

2.5    Administration Instructions

Food and Levofloxacin Tablets Levofloxacin Tablets can be administered without regard to food.

Hydration for Patients Receiving Levofloxacin tablets Adequate hydration of patients receiving oral levofloxacin 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)].

---

Dosage should be adjusted according to severity of pain and 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.

5 mg/300 mg: The usual adult dose is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed eight tablets.

7.5 mg/300 mg: The usual adult dose is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed six tablets.

10 mg/300 mg: The usual adult dose is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed six tablets.