Are there any reports of levetiracetam-induced thrombocytopenia?/nA 49-year-old man with a brain tu

Fråga: Are there any reports of levetiracetam-induced thrombocytopenia?

A 49-year-old man with a brain tumour and epilepsy had levetiracetam added and phenytoin and phenobarbital doses increased at the same time. Twenty days later, his thrombocyte levels had decreased to 7 (reference value 150-400) from 314 10E9/L and levetiracetam was withdrawn. Sertraline was also withdrawn. The thrombocyte count did not increase until immunoglobulin was given during days five to ten after withdrawal of sertraline and levetiracetam. Irregular antibodies for thrombocytes were observed in the presence of levetiracetam but not sertraline, which support that this was a levetiracetam-induced thrombocytopenia. The case has been reported to the regional pharmacovigilance centre.

Sammanfattning: Only one published case report of levetiracetam-associated thrombocytopenia was found in the literature. In the Swedish and international adverse drug reaction registries there are 15 cases of thrombocytopenia associated with levetiracetam treatment. Thrombocytopenia is possibly a previously unknown, rare side effect that can develop during levetiracetam treatment.

Svar: Levetiracetam is a quite new antiepileptic drug that has been on the Swedish market since 2000 (1). Thus, previously unknown side effects might still be revealed.

Only one published case report of levetiracetam-associated thrombocytopenia has been found in the literature. It concerns a 16 year-old girl who first developed a chronic immune-mediated thrombocytopenia during treatment with valproid acid, oxcarbazepin and phenytoin. All drugs were withdrawn and her thrombocyte count increased. However, following the initiation of levetiracetam monotherapy, her thrombocyte decreased again and she developed bleedings (2).

So far, only eleven cases of levetiracetam side effects have been reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC). One of these reports concerns a 19-year old woman with thrombocytopenia, which improved after withdrawal of the drug. However, several other factors, such as polypharmacy, infection and a previous thrombocytopenia, might also have contributed to, or caused the reaction. (1).

The WHO adverse drug reaction-monitoring centre has received totally 576 adverse drug reaction reports associated with levetiracetam treatment of which 14 reports concerns thrombocytopenia. However, these reports are not evaluated as to the cause relationship, due to differences among reporting countries (3).

The manufacturer of Keppra (levetiracetam), UCB, did not want to send any information according to their internal policy. 1 Swedis (The Swedish Drug Information System) (cited 2003-06-18) 2 Hartmann H, Schumacher U, Seeck M. Verschlechterung einer Immunthrombopenie unter Monotherapie mit Levetiracetam. Aktuel Neurol 2002;29:467-8. 3 Vigibase: WHO:s adverse drug reactions database (cited 2003-06-18)