indication

Used as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

mechanism of action

The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures. Levetiracetam did not inhibit single seizures induced by maximal stimulation with electrical current or different chemoconvulsants and showed only minimal activity in submaximal stimulation and in threshold tests. Protection was observed, however, against secondarily generalized activity from focal seizures induced by pilocarpine and kainic acid, two chemoconvulsants that induce seizures that mimic some features of human complex partial seizures with secondary generalization. Levetiracetam also displayed inhibitory properties in the kindling model in rats, another model of human complex partial seizures, both during kindling development and in the fully kindled state. The predictive value of these animal models for specific types of human epilepsy is uncertain. Levetiracetam is thought to stimulate synaptic vesicle protein 2A (SV2A), inhibiting neurotransmitter release.

toxicity

Side effects include aggression, agitation, coma, drowsiness, reduced consciousness, slowed breathing

biotransformation

The major metabolic pathway of levetiracetam (24% of dose) is an enzymatic hydrolysis of the acetamide group. No CYP450 metabolism detected.

absorption

Rapidly and almost completely absorbed after oral administration (99%). Peak plasma concentrations occurring in about an hour following oral administration in fasted subjects.

half life

6-8 hours

route of elimination

Sixty-six percent (66%) of the dose is renally excreted unchanged. The metabolites have no known pharmacological activity and are renally excreted. The mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption.

drug interactions

Carbamazepine: Concomitant therapy may results in additive adverse CNS effects.

Triprolidine: The CNS depressants, Triprolidine and Levetiracetam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.