Carbamazepine toxicity during combination therapy with levetiracetam: a pharmacodynamic interaction

Levetiracetam is a novel antiepileptic drug with an unknown mechanism of action. To-date levetiracetam is not known to be associated with any clinically significant pharmacokinetic interaction. Similarly, levetiracetam has not been associated with any pharmacodynamic interactions. We present four patients with severe refractory epilepsy in whom introduction of levetiracetam led to disabling symptoms compatible with carbamazepine toxicity requiring either carbamazepine dose reduction or levetiracetam withdrawal. As carbamazepine and carbamazepine-epoxide blood levels were not altered during levetiracetam co-medication, a pharmacodynamic interaction is suggested. Therefore, during levetiracetam co-medication with carbamazepine, patients should be monitored closely for symptoms of carbamazepine toxicity.