Clobazam

Actions

• Increases frequency of GABA-mediated chloride channel opening.

Metabolism

Hepatic

Enzymes involved

• CYP3A4
• CYP2B6
• CYP2C19
• CYP2C18

Elimination

Renal ~94%

Enzyme inhibition

CYP2D6

Half-life

36–42 hours

Plasma protein binding

80-90%

Important side-effects

Serious Dermatological Reactions, including Stevens-Johnson syndrome and TEN.

Suicidal behavior and ideation.

CNS depression. Concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality.

Indications

Adjunctive treatment of generalized tonic-clonic, complex partial, and myoclonic seizures.

Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome.

Dosing recommendation

Start with 10 mg/day.

Increase to 20 mg/day after 1–2 weeks.

Target dose: 10–40 mg/day divided in 1-2 doses.

Renal impairment

No dose adjustment is required for patients with mild to moderate renal impairment. Insufficient data exist on the safety of clobazam in patients with severe renal failure.

Hepatic impairment

Dose adjustment is recommended in patients with mild to moderate hepatic impairment (Child-Pugh score 5-9).