DOSAGE AND ADMINISTRATION
KEPPRA is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.
KEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.
KEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized 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 14 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.
KEPPRA is given orally with or without food.
Table 14: KEPPRA Tablet Weight-Based Dosing Guide For Children | Daily Dose
|
|---|
| Patient Weight | 20 mg/kg/day
(BID dosing) | 40 mg/kg/day
(BID dosing) | 60 mg/kg/day
(BID dosing) |
| 20.1-40 kg | 500 mg/day
(1 x 250 mg
tablet BID) | 1000 mg/day
(1 x 500 mg
tablet BID) | 1500 mg/day
(1 x 750 mg
tablet BID) |
| >40 kg | 1000 mg/day
(1 x 500 mg
tablet BID) | 2000 mg/day
(2 x 500 mg
tablets BID) | 3000 mg/day
(2 x 750 mg
tablets BID) |
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:
Daily dose (mg/kg/day) x patient weight (kg)
Total daily dose (mL/day) = ———————————————————————
100 mg/mL
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.
Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
Primary Generalized Tonic-Clonic Seizures
Adults 16 Years And Older
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.
Pediatric Patients Ages 6 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 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). 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 Table 14 for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.
Adult Patients With Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 15. 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:
[140-age (years)] x weight (kg)
CLcr = ————————————————— (x 0.85 for female patients)
72 x serum creatinine (mg/dL)
Table 15: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function | Group | Creatinine Clearance
(mL/min) | Dosage
(mg) | Frequency |
| 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. |
| Normal | > 80 | 500 to 1,500 | Every 12 h |
| Mild | 50 – 80 | 500 to 1,000 | Every 12 h |
| Moderate | 30 – 50 | 250 to 750 | Every 12 h |
| Severe | < 30 | 250 to 500 | Every 12 h |
| ESRD patients using dialysis | ---- | 500 to 1,000 | 1Every 24 h |
|
