Clobazam is a 1,5-benzodiazepine derivative used primarily as an adjunctive therapy for Lennox-Gastaut syndrome (LGS) and other forms of epilepsy. It is also indicated for the short-term management of anxiety disorders. It acts as a positive allosteric modulator at the GABA-A receptor, enhancing inhibitory neurotransmission in the CNS. In India, it is a widely used anticonvulsant and anxiolytic, available under multiple brands.
Adult: Anxiety: 10-20 mg/day in divided doses or as a single dose at night. Max: 30 mg/day. Epilepsy (LGS): Start at 5-10 mg/day, titrate up to 20-40 mg/day based on response and tolerability. Max recommended: 40 mg/day.
Note: Can be taken with or without food. Tablet should be swallowed whole with water. For epilepsy, doses are typically divided twice daily. Do not crush or chew. Avoid abrupt discontinuation; taper dose gradually over weeks to months to avoid withdrawal seizures or symptoms.
Clobazam binds to a specific, high-affinity site on the GABA-A receptor complex, distinct from the classical benzodiazepine binding site. This binding facilitates the opening of the chloride ion channel upon GABA binding, increasing the frequency of channel opening. The resulting influx of chloride ions hyperpolarizes the neuronal membrane, making it less excitable and producing CNS depressant effects.
Pregnancy: Category D (as per some regulatory bodies; FDA Pregnancy Category is now part of the Pregnancy and Lactation Labeling Rule). Evidence of human fetal risk. Benzodiazepines cross the placenta and may cause fetal harm, including 'floppy infant syndrome', neonatal withdrawal, and possible teratogenicity (cleft lip/palate). Use only if clearly needed and benefit outweighs risk. Avoid during first trimester if possible. Monitor neonate for withdrawal symptoms.
Driving: IMPAIRS ALERTNESS. Patients should not drive or operate heavy machinery, especially during initiation and dose adjustment, until individual response is known. Effects are potentiated by alcohol.
| Alcohol | Potentiates CNS depression, respiratory depression, psychomotor impairment. | Major |
| Other CNS Depressants (Opioids, Barbiturates, other Benzodiazepines, Sedative Antihistamines) | Additive CNS depression, increased risk of respiratory depression, sedation, coma. | Major |
| Strong CYP2C19 Inhibitors (e.g., Omeprazole, Fluconazole, Fluvoxamine) | Increases levels of active metabolite N-desmethylclobazam, leading to enhanced effects and toxicity. | Moderate |
| Strong CYP3A4 Inducers (e.g., Carbamazepine, Phenytoin, Rifampicin, St. John's Wort) | Decreases clobazam levels, potentially reducing efficacy. | Moderate |
| Sodium Valproate | May increase levels of N-desmethylclobazam. | Moderate |
| Theophylline | May antagonize the sedative effects of clobazam. | Minor |