KEPPRA Oral solution Ref.[116930] Active ingredients: Levetiracetam

Source: European Medicines Agency (EU)  Revision Year: 2026  Publisher: UCB Pharma SA, Allée de la Recherche 60, B-1070 Brussels, Belgium

4.1. Therapeutic indications

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

  • in the treatment of partial onset seizures with or without secondary generalisation in adults, adolescents, children and infants from 1 month of age with epilepsy.
  • in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy.
  • in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.

4.2. Posology and method of administration

Posology

Partial onset seizures

The recommended dosing for monotherapy (from 16 years of age) and adjunctive therapy is the same; as outlined below.

All indications

Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more

The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. However, a lower initial dose of 250 mg twice daily may be given based on physician assessment of seizure reduction versus potential side effects. This can be increased to 500 mg twice daily after two weeks.

Depending upon the clinical response and tolerability, the daily dose can be increased up to 1500 mg twice daily. Dose changes can be made in 250 mg or 500 mg twice daily increases or decreases every two to four weeks.

Adolescents (12 to 17 years) weighing below 50 kg and children from 1 month of age

The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to weight, age and dose. Refer to Paediatric population section for dosing adjustments based on weight.

Discontinuation

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 weighing 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).

Special populations

Elderly (65 years and older)

Adjustment of the dose is recommended in elderly patients with compromised renal function (see "Renal impairment" below).

Renal impairment

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 weighing 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 adolescent patients weighing more than 50 kg with impaired renal function:

GroupCreatinine clearance
(ml/min/1.73m²)
Dose and frequency
Normal≥80500 to 1500 mg twice daily
Mild50-79500 to 1000 mg twice daily
Moderate30-49250 to 750 mg twice daily
Severe<30250 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 adolescent patients weighing less than 50 kg with impaired renal function:

GroupCreatinine
clearance
(ml/min/1.73m²)
Dose and frequency1
Infants 1 to less than 6
months
Infants 6 to 23 months, children
and adolescents weighing less
than 50 kg
Normal≥807 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
Mild50-797 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
Moderate30-493.5 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<303.5 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.

Hepatic impairment

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.

Paediatric population

The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to age, weight and dose.

Keppra oral solution is the preferred formulation for use in infants and children under the age of 6 years. 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.

Monotherapy

The safety and efficacy of Keppra in children and adolescents below 16 years as monotherapy treatment have not been established.

No data are available.

Adolescents (16 and 17 years of age) weighing 50 kg or more with partial onset seizures with or without secondary generalisation with newly diagnosed epilepsy

Please refer to the above section on Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more.

Add-on therapy for infants aged 6 to 23 months, children (2 to 11 years) and adolescents (12 to 17 years) weighing less than 50 kg

The initial therapeutic dose is 10 mg/kg twice daily.

Depending upon the clinical response and tolerability, the dose can be increased by 10 mg/kg twice daily every 2 weeks 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 for all indications.

Dose in children 50 kg or greater is the same as in adults for all indications.

Please refer to the above section on Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more for all indications.

Dose recommendations for infants from 6 months of age, children and adolescents:

WeightStarting dose:
10 mg/kg twice daily
Maximum dose:
30 mg/kg twice daily
6 kg160 mg (0.6 ml) twice daily180 mg (1.8 ml) twice daily
10 kg1100 mg (1 ml) twice daily300 mg (3 ml) twice daily
15 kg1150 mg (1.5 ml) twice daily450 mg (4.5 ml) twice daily
20 kg1200 mg (2 ml) twice daily600 mg (6 ml) twice daily
25 kg250 mg twice daily750 mg twice daily
From 50 kg2500 mg twice daily1500 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.

Add-on therapy for infants aged from 1 month to less than 6 months

The initial therapeutic dose is 7 mg/kg twice daily.

Depending upon the clinical response and tolerability, the dose can be increased by 7 mg/kg twice daily every 2 weeks up to recommended dose of 21 mg/kg twice daily. Dose changes should not exceed increases or decreases of 7 mg/kg twice daily every two weeks. The lowest effective dose should be used.

Infants should start the treatment with Keppra 100 mg/ml oral solution.

Dose recommendations for infants aged from 1 month to less than 6 months:

WeightStarting dose:
7 mg/kg twice daily
Maximum dose:
21 mg/kg twice daily
4 kg28 mg (0.3 ml) twice daily84 mg (0.85 ml) twice daily
5 kg35 mg (0.35 ml) twice daily105 mg (1.05 ml) twice daily
7 kg49 mg (0.5 ml) twice daily147 mg (1.5 ml) twice daily

Three presentations are available:

  • A 300 ml bottle with a 10 ml oral syringe (delivering up to 1000 mg levetiracetam) graduated every 0.25 ml (corresponding to 25 mg).
    This presentation should be prescribed for children aged 4 years and older, adolescents and adults.
  • A 150 ml bottle with a 5 ml oral syringe (delivering up to 500 mg levetiracetam) graduated every 0.1 ml (corresponding to 10 mg) from 0.3 ml to 5 ml and every 0.25 ml (corresponding to 25 mg) from 0.25 ml to 5 ml.
    In order to ensure the accuracy of the dosing, this presentation should be prescribed for infants and young children aged from 6 months to less than 4 years.
  • A 150 ml bottle with a 1 ml oral syringe (delivering up to 100 mg levetiracetam) graduated every 0.05 ml (corresponding to 5 mg)
    In order to ensure the accuracy of the dosing, this presentation should be prescribed for infants aged 1 month to less than 6 months.

Method of administration

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.

4.9. Overdose

Symptoms

Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Keppra overdoses.

Management of overdose

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.

6.3. Shelf life

3 years.

After first opening: 7 months.

6.4. Special precautions for storage

Store in the original bottle in order to protect from light.

6.5. Nature and contents of container

300 ml amber glass bottle (type III) with a white child resistant closure (polypropylene) in a cardboard box also containing a 10 ml graduated oral syringe (polypropylene, polyethylene) and an adaptor for the syringe (polyethylene).

150 ml amber glass bottle (type III) with a white child resistant closure (polypropylene) in a cardboard box also containing a 5 ml graduated oral syringe (polypropylene, polyethylene) and an adaptor for the syringe (polyethylene).

150 ml amber glass bottle (type III) with a white child resistant closure (polypropylene) in a cardboard box also containing a 1 ml graduated oral syringe (polypropylene, polyethylene) and an adaptor for the syringe (polyethylene).

6.6. Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.