Source: European Medicines Agency (EU) Revision Year: 2018 Publisher: UCB Pharma SA, Allée de la Recherche 60, B-1070 Brussels, Belgium
Keppra is indicated as monotherapy in the treatment of partial onset seizures with or without secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed epilepsy.
Keppra is indicated as adjunctive therapy:
Keppra therapy can be initiated with either intravenous or oral administration. Conversion to or from oral to intravenous administration can be done directly without titration. The total daily dose and frequency of administration should be maintained.
The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg twice daily.
The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment.
Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decreases every two to four weeks.
There is no experience with administration of intravenous levetiracetam for longer period than 4 days.
If levetiracetam has to be discontinued it is recommended to withdraw it gradually (e.g. in adults and adolescents weighing more than 50 kg: 500 mg decreases twice daily every two to four weeks; in children and adolescents weighting less than 50 kg: dose decrease should not exceed 10 mg/kg twice daily every two weeks).
Adjustment of the dose is recommended in elderly patients with compromised renal function (see “Renal impairment” below).
The daily dose must be individualised according to renal function.
For adult patients, refer to the following table and adjust the dose as indicated. To use this dosing table, an estimate of the patient’s creatinine clearance (CLcr) in ml/min is needed. The CLcr in ml/min may be estimated from serum creatinine (mg/dl) determination, for adults and adolescents weighting 50 kg or more, the following formula:
CLcr (ml/min) = [140-age (years)] x weight (kg) / 72 x serum creatinine (mg/dl) (x 0.85 for women)
Then CLcr is adjusted for body surface area (BSA) as follows:
CLcr (ml/min/1.73 m²) = CLcr (ml/min) / BSA subject (m²) x 1.73
Dosing adjustment for adult and adolescents patients weighing more than 50 kg with impaired renal function:
| Group | Creatinine clearance (ml/min/1.73m²) | Creatinine clearance Dose and frequency |
|---|---|---|
| Normal | >80 | 500 to 1,500 mg twice daily |
| Mild | 50-79 | 500 to 1,000 mg twice daily |
| Moderate | 30-49 | 250 to 750 mg twice daily |
| Severe | <30 | 250 to 500 mg twice daily |
| End-stage renal disease patients undergoing dialysis1 | - | 500 to 1,000 mg once daily2 |
1 A 750 mg loading dose is recommended on the first day of treatment with levetiracetam.
2 Following dialysis, a 250 to 500 mg supplemental dose is recommended.
For children with renal impairment, levetiracetam dose needs to be adjusted based on the renal function as levetiracetam clearance is related to renal function. This recommendation is based on a study in adult renally impaired patients.
The CLcr in ml/min/1.73 m² may be estimated from serum creatinine (mg/dl) determination, for young adolescents and children using the following formula (Schwartz formula)
CLcr (ml/min/1.73 m²) = Height (cm) x ks / Serum Creatinine (mg/dl)
ks = 0.55 in Children to less than 13 years and in adolescent female; ks= 0.7 in adolescent male
Dosing adjustment for children and adolescents patients weighing less than 50 kg with impaired renal function:
| Group | Creatinine clearance (ml/min/1.73m²) | Dose and frequency | |
|---|---|---|---|
| Children from 4 years and adolescents weighing less than 50 kg | |||
| Normal | >80 | 10 to 30 mg/kg (0.10 to 0.30 ml/kg) twice daily | |
| Mild | 50-79 | 10 to 20 mg/kg (0.10 to 0.20 ml/kg) twice daily | |
| Moderate | 30-49 | 5 to 15 mg/kg (0.05 to 0.15 ml/kg) twice daily | |
| Severe | <30 | 5 to 10 mg/kg (0.05 to 0.10 ml/kg) twice daily | |
1 A 15 mg/kg (0.15 ml/kg) loading dose is recommended on the first day of treatment with levetiracetam.
2 Following dialysis, a 5 to 10 mg/kg (0.05 to 0.10 ml/kg) supplemental dose is recommended.
No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate the renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is <60 ml/min/1.73 m².
The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to age, weight and dose.
The safety and efficacy of Keppra in children below and adolescents 16 years as monotherapy treatment have not been established.
No data are available.
The initial therapeutic dose is 10 mg/kg twice daily.
Depending upon the clinical response and tolerability, the dose can be increased up to 30 mg/kg twice daily. Dose changes should not exceed increases or decreases of 10 mg/kg twice daily every two weeks. The lowest effective dose should be used.
Dose in children 50 kg or greater is the same as in adults.
Dose recommendations for children and adolescents:
| Weight | Starting dose: 10 mg/kg twice daily | Maximum dose: 30 mg/kg twice daily |
|---|---|---|
| 15 kg1 | 150 mg twice daily | 450 mg twice daily |
| 20 kg1 | 200 mg twice daily | 600 mg twice daily |
| 25 kg | 250 mg twice daily | 750 mg twice daily |
| From 50 kg2 | 500 mg twice daily | 1500 mg twice daily |
1 Children 25 kg or less should preferably start the treatment with Keppra 100 mg/ml oral solution.
2 Dose in children and adolescents 50 kg or more is the same as in adults.
The safety and efficacy of Keppra concentrate for solution for infusion in infants and children less than 4 years have not been established.
Currently available data are described in sections 4.8, 5.1, and 5.2 but no recommendation on a posology can be made.
Keppra concentrate is for intravenous use only and the recommended dose must be diluted in at least 100 ml of a compatible diluent and administered intravenously as a 15-minute intravenous infusion (see section 6.6).
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Keppra overdoses.
There is no specific antidote for levetiracetam. Treatment of an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60% for levetiracetam and 74% for the primary metabolite.
3 years.
From a microbiological point of view, the product should be used immediately after dilution. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
This medicinal product does not require any special storage conditions.
For storage conditions of the diluted medicinal product, see section 6.3.
5 ml glass vial (type I) closed by a polytetrafluoroethylene grey chlorobutyl rubber stopper or an uncoated grey bromobutyl rubber stopper and sealed with an aluminium/polypropylene flip cap.
Each carton contains 10 vials.
See Table 1 for the recommended preparation and administration of Keppra concentrate for solution for infusion to achieve a total daily dose of 500 mg, 1,000 mg, 2,000 mg, or 3,000 mg in two divided doses.
Table 1. Preparation and administration of Keppra concentrate for solution for infusion:
| Dose | Withdrawal Volume | Volume of Diluent | Infusion Time | Frequency of Administration | Total Daily Dose |
|---|---|---|---|---|---|
| 250 mg | 2.5 ml (half 5 ml vial) | 100 ml | 15 minutes | Twice daily | 500 mg/day |
| 500 mg | 5 ml (one 5 ml vial) | 100 ml | 15 minutes | Twice daily | 1000 mg/day |
| 1000 mg | 10 ml (two 5 ml vials) | 100 ml | 15 minutes | Twice daily | 2000 mg/day |
| 1500 mg | 15 ml (three 5 ml vials) | 100 ml | 15 minutes | Twice daily | 3000 mg/day |
This medicinal product is for single use only, any unused solution should be discarded.
Keppra concentrate for solution for infusion was found to be physically compatible and chemically stable for at least 24 hours when mixed with the following diluents and stored in PVC bags at controlled room temperature 15-25°C.
Diluents:
Medicinal product with particulate matter or discoloration should not be used. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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