Clinical Information

Clobazam is a broad spectrum, antiepileptic drug used for various types of seizures, Lennox-Gastaut syndrome (a type of childhood onset epilepsy), and migraine prophylaxis. Clobazam blocks voltage-dependent sodium channels, potentiates gamma-aminobutyric acid (GABA) activity at some of the GABA receptors, and inhibits potentiation of the glutamate receptor and carbonic anhydrase enzyme, all of which contribute to its antiepileptic and antimigraine efficacy.

In general, clobazam shows favorable pharmacokinetics with good absorption (1-4 hours for the immediate-release formulation), low protein binding, and minimal hepatic metabolism. Elimination is predominantly renal, and it is excreted unchanged in the urine with an elimination half-life of approximately 21 hours. As with other anticonvulsant drugs eliminated by the renal system, patients with impaired kidney function exhibit decreased clobazam clearance and a prolonged elimination half-life.

Serum concentrations of other anticonvulsant drugs are not significantly affected by the concurrent administration of clobazam, with the exception of patients on phenytoin whose serum concentrations can increase after the addition of clobazam. Other drug-drug interactions include the coadministration of phenobarbital, phenytoin, or carbamazepine, which can result in decreased clobazam concentrations. In addition, concurrent use of posaconazole and clobazam may result in the elevation of clobazam serum concentrations. Therefore, changes in cotherapy with these medications (phenytoin, carbamazepine, posaconazole, or phenobarbital) may require dose adjustment of clobazam, and therapeutic drug monitoring can be helpful. The most common adverse drug effects associated with clobazam include weight loss, loss of appetite, somnolence, dizziness, coordination problems, memory impairment, and paresthesia.