Keppra (UCB Pharma)
250 mg, 500 mg and 1000 mg film-coated tablets
Approved indication: epilepsy
Australian Medicines Handbook Section 16.1
Over the past few years several drugs have been developed as `add-on therapy' for patients whose epilepsy is not well controlled by conventional treatment(see `New antiepileptic drugs' Aust Prescr 1999;22:61-3). Levetiracetam is a new drug which has been approved as add-on therapy for patients with partial onset seizures with or without secondary generalisation.
The mechanism of action is unknown. Levetiracetam does not act in the same way as other antiepileptic drugs.
Patients take levetiracetam twice a day. Absorption is rapid and unaffected by food. Most of the drug is excreted unchanged in the urine. The dose should be adjusted if renal function is reduced. Although 24% of each dose is metabolised no dose adjustment is needed in hepatic impairment unless liver function is severely reduced.
A double-blind trial compared levetiracetam with placebo as add-on therapy for 294 patients with refractory partial seizures. The frequency of seizures was halved in 33% of patients taking levetiracetam 1000 mg daily and in 40%of patients taking 3000 mg daily. Only 11% of the placebo group had similar reductions in seizure frequency. Patients taking the higher dose of levetiracetam had a 30% reduction in the weekly frequency of seizures relative to placebo.1
The common adverse effects of levetiracetam are somnolence, asthenia and headache. If treatment has to stop it should be gradually withdrawn. In the clinical trials 13% of patients given levetiracetam developed an infection compared with 7% of patients given a placebo. A few patients will have a decreased white blood cell count. Some patients taking levetiracetam will develop behavioural problems such as hostility, particularly in the first few weeks of treatment. There have been a few reports of psychotic symptoms.
As levetiracetam is mainly excreted in urine it is unlikely to have significant interactions with drugs metabolised by the liver. It does not inhibit the cytochromeP450 system. The pharmacokinetics of levetiracetam are unchanged by phenytoin, carbamazepine, phenobarbitone, lamotrigine and gabapentin.
The studies show that levetiracetam is a better adjunctive therapy than placebo, but its long-term safety is unknown. There is also no information about its use in children or how it compares with the other add-on therapies.
