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:
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.
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 infants older than 6 months, children and adolescents weighting less than 50 kg: dose decrease should not exceed 10 mg/kg twice daily every two weeks; in infants (less than 6 months): dose decrease should not exceed 7 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) | 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, children and infants, using the following formula (Schwartz formula):
CLcr (ml/min/1.73 m²) = Height (cm) x ks / Serum Creatinine (mg/dl)
ks= 0.45 in Term infants to 1 year old; ks= 0.55 in Children to less than 13 years and in adolescent female; ks= 0.7 in adolescent male
Dosing adjustment for infants, children and adolescents patients weighing less than 50 kg with impaired renal function:
| Group | Creatinine clearance (ml/min/1.73m²) | Dose and frequency1 | |
|---|---|---|---|
| Infants 1 to less than 6 | Infants 6 to 23 months, children and adolescents weighing less than 50 kg | ||
| Normal | >80 | 7 to 21 mg/kg (0.07 to 0.21 ml/kg) twice daily | 10 to 30 mg/kg (0.10 to 0.30 ml/kg) twice daily |
| Mild | 50-79 | 7 to 14 mg/kg (0.07 to 0.14 ml/kg) twice daily | 10 to 20 mg/kg (0.10 to 0.20 ml/kg) twice daily |
| Moderate | 30-49 | 3.5 to 10.5 mg/kg (0.035 to 0.105 ml/kg) twice daily | 5 to 15 mg/kg (0.05 to 0.15 ml/kg) twice daily |
| Severe | <30 | 3.5 to 7 mg/kg (0.035 to 0.07 ml/kg) twice daily | 5 to 10 mg/kg (0.05 to 0.10 ml/kg) twice daily |
| End-stage renal disease patients undergoing dialysis | -- | 7 to 14 mg/kg (0.07 to 0.14 ml/kg) once daily2,4 | 10 to 20 mg/kg (0.10 to 0.20 ml/kg) once daily3,5 |
1 Keppra oral solution should be used for doses under 250 mg, for doses not multiple of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets.
2 A 10.5 mg/kg (0.105 ml/kg) loading dose is recommended on the first day of treatment with levetiracetam.
3 A 15 mg/kg (0.15 ml/kg) loading dose is recommended on the first day of treatment with levetiracetam.
4 Following dialysis, a 3.5 to 7 mg/kg (0.035 to 0.07 ml/kg) supplemental dose is recommended.
5 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 tablet formulation is not adapted for use in infants and children under the age of 6 years. Keppra oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases Keppra oral solution should be used.
The safety and efficacy of Keppra in children and adolescents below 16 years as monotherapy treatment have not been established.
No data are available.
Keppra oral solution is the preferred formulation for use in infants and children under the age of 6 years.
For children 6 years and above, Keppra oral solution should be used for doses under 250 mg, for doses not multiple of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets.
The lowest effective dose should be used. The starting dose for a child or adolescent of 25kg should be 250mg twice daily with a maximum dose of 750mg twice daily. Dose in children 50 kg or greater is the same as in adults.
The oral solution is the formulation to use in infants.
The film-coated tablets must be taken orally, swallowed with a sufficient quantity of liquid and may be taken with or without food. After oral administration the bitter taste of levetiracetam may be experienced. The daily dose is administered in two equally divided doses.
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Keppra overdoses.
After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. 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.
This medicinal product does not require any special storage conditions.
Aluminium/PVC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 100, 120 film- coated tablets and multipacks containing 200 (2 packs of 100) film-coated tablets.
Aluminium/PVC perforated unit dose blisters placed into cardboard boxes containing 100 × 1 film- coated tablet.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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