Levetiracetam is an analogue of piracetam (). It is used as an adjunct in the treatment of partial seizures with or without secondary generalisations in adults and children aged 4 years and over; in the UK, adults and adolescents aged 16 years and over may also be given levetiracetam as monotherapy for this indication. In addition, levetiracetam is licensed for adjunctive use in the treatment of myoclonic seizures in adults and children aged 12 years and over with juvenile myoclonic epilepsy. It is also licensed for use as an adjunct in the treatment of primary generalised tonic-clonic seizures in adults and children with idiopathic generalised epilepsy; for this indication, in the UK, licensed use is restricted to children aged 12 years and over, whereas in the United States of America (US and USA), it is licensed from 6 years of age. The daily oral dose of levetiracetam is given in two divided doses.
- The initial adult dose when used as an adjunct is 1 g on the first day of treatment; thereafter, the daily dose may be increased in steps of 1 g every 2 to 4 weeks until effective antiepileptic control is achieved, up to a maximum dose of 3 g daily. The initial dose in children weighing less than 50 kg is 20 mg/kg daily which may be increased in steps of 20 mg/kg every 2 weeks to a maximum of 60 mg/kg daily.
Children and adolescents weighing 50 kg or more should be given the usual adult dose. When used as monotherapy, the initial dose of levetiracetam is 500 mg daily, increased after 2 weeks to 1 g daily. Further increases may be made in steps of 500 mg every 2 weeks up to a maximum of 3 g daily. When oral use is not feasible, levetiracetam may be given by intravenous infusion over 15 minutes in doses similar to those used orally; as with the oral formulation, details of licensed uses and ages may vary from country to country. UK licensed product information states that there has been no experience with the use of intravenous levetiracetam for more than 4 days. Reduced doses are recommended in renal and severe hepatic impairment. As with other antiepileptics, withdrawal of levetiracetam therapy or transition to or from another type of antiepileptic therapy should be made gradually to avoid precipitating an increase in the frequency of seizures. UK licensed product information recommends reducing the daily dose in adults by 1 g every 2 to 4 weeks; in children, the dose reduction should not exceed 20 mg/kg every 2 weeks. For a discussion on whether or not to withdraw antiepileptic therapy in seizure-free patients.
Administration in children. Licensed indications and doses of levetiracetam in children vary from country to country, see Uses and Administration, above. It is mainly used for partial and myoclonic seizures, and in idiopathic generalised epilepsy, often as an adjunct. A retrospective review of 122 children aged from 1 month to 2 years given levetiracetam either as monotherapy (48 patients) or adjunctive therapy (74 patients) found that 70 achieved seizure remission. Of these, a longer duration of remission was seen in those receiving less than 30 mg/kg daily of levetiracetam. A case series of 3 infants aged from 2 days to 3 months reported that levetiracetam 30 mg/kg daily was effective in the treatment of refractory neonatal seizures.
Administration in hepatic impairment. No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, creatinine clearance (CC) may underestimate concomitant renal impairment, and UK licensed product information recommends that the usual adult maintenance dose should be reduced by 50% in those with a CC of less than 70 mL/mfnute.
Administration in renal impairment. Reduced doses of levetiracetam are recommended for patients with renal impairment. Suitable daily doses according to UK and US licensed product information, based on creatinine clearance (CC) and given in 2 divided doses, are:
- CC 50 to 79 mL/mrnute: 1 to 2 g
- CC 30 to 49 mL/mrnute: 500 mg to 1.5 g
- CC less than 30 mL/minute: 500 mg to 1 g
Patients receiving dialysis may be given a loading dose of 750 mg when starting levetiracetam followed by doses of 500 mg to 1 g once daily; a supplemental dose of 250 to 500 mg is recommended after dialysis.
Doses may be given orally or intravenously, as necessary. See also above for dosage recommendations in those patients with severe hepatic impairment and concomitant renal impairment.
Epilepsy. Levetiracetam is used in epilepsy () as an adjunct or monotherapy in the management of partial seizures with or without secondary generalisation. It is also used as an adjunct in myoclonic seizures and for generalised tonic-clonic seizures, although valproate is the drug of choice in the latter where these are associated with the syndrome of primary generalised epilepsy. Levetiracetam may be considered as second-line drug for atonic or tonic seizures, and has been tried in Lennox-Gastaut syndrome and in juvenile absence epilepsy in children, levetiracetam has also been tried as adjunctive therapy for nonconvulsive status epilepticus, in infantile spasms, and in severe myoclonic epilepsy of infancy, and as monotherapy in partial and generalised epilepsy
Movement disorders. Levetiracetam may be of benefit in some movement disorders. It has been tried in antipsychotic-induced tardive dyskinesia and with equivocal benefit in levodopa-induced tardive dyskinesia (see under Extrapyramidal Disorders). There is also limited evidence of benefit with levetiracetam for the treatment of chorea () in Huntington’s disease and in paroxysmal kinesigenic choreoathetosis.
Muscle spasm. Levetiracetam has been tried with some success in Meige’s syndrome, and hemifacial spasm. For use in stiff-man syndrome see below.
Psychiatric disorders. Levetiracetam has psychotropic properties and has been tried in the management of anxiety disorders () including social anxiety disorder (see Phobic Disorders), post-traumatic stress disorder (), and panic disorder (). There is also limited evidence from case reports and small open-label studies that levetiracetam may be of benefit in the treatment of bipolar disorder ().
Restless legs syndrome. Levetiracetam has been reported to be of benefit in the treatment of refractory restless legs syndrome (see Sleep-associated Movement Disorders).
Status epilepticus. Levetiracetam has been tried, with some success, in the management of nonconvulsive status epilepticus and refractory status epilepticus.
Stiff-man syndrome. In a report of a patient with stiff-man syndrome, substitution of levetiracetam for previous valproate therapy (because of suspected valproate-induced parkinsonism) resulted in complete suppression of paroxysmal spasms; benefit was sustained with continued therapy over 2 years of follow-up.
Tremor. A beta blocker is often the first drug used in patients with essential tremor who require regular treatment (); however, levetiracetam has also been tried with some success. Benefit was also reported with levetiracetam in the treatment of tremor secondary to multiple sclerosis.
The information about drugs (tablets, pills, capsules, creams, solution, nasal spray, inhaler) around the world.
Argentina: Keppra; Levron;
Czech Republic: Keppra;
Hong Kong: Keppra;
The Netherlands: Keppra;
New Zealand: Keppra;
South Africa: Keppra;
United Kingdom (UK): Keppra;
United States of America (US and USA): Keppra.
Selections from the book: “Martindale: The Complete Drug Reference. Thirty-sixth edition”. Pharmaceutical Press. 2009