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# Clobazam (Oral Formulation)
## Overview
Clobazam is a benzodiazepine derivative with anticonvulsant properties. It acts as a positive allosteric modulator of the GABA-A receptor, enhancing inhibitory neurotransmission.
## Primary Indications
* Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.
* Off-label use for other seizure types, including absence seizures and myoclonic seizures.
## Adult Dosing
* **Lennox-Gastaut Syndrome:** Initial dose is typically 5 mg twice daily. Increase dose by 5 mg every week as tolerated to a maximum of 10 mg twice daily (total daily dose 20 mg). Some patients may benefit from up to 20 mg twice daily (total daily dose 40 mg).
* **Other Seizure Types (Off-label):** Dosing varies widely. A common starting point is 5 mg once or twice daily, titrating slowly based on response and tolerability. Maximum doses are not well-established and should be guided by clinical judgment and local protocols.
## Pediatric Dosing (2 to <10 years of age or <30 kg)
* **Lennox-Gastaut Syndrome:** Initial dose is typically 2.5 mg twice daily. Increase dose by 2.5 mg every week as tolerated to a maximum of 5 mg twice daily (total daily dose 10 mg).
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. No specific dosage adjustments are established, but a lower starting dose and slower titration may be warranted.
* **Renal Impairment:** No specific dosage adjustments are established, but use with caution.
## Contraindications
* Hypersensitivity to clobazam or other benzodiazepines.
* Severe hepatic impairment.
## Adverse Effects
Common adverse effects include somnolence, decreased appetite, aggression, irritability, ataxia, constipation, nausea, vomiting, fatigue, and drooling. Serious adverse effects include serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), paradoxical reactions (increased seizure frequency, agitation, hostility), respiratory depression, and potential for dependence and withdrawal.
## Key Drug Interactions
* **CNS Depressants (e.g., alcohol, opioids, other sedatives):** Increased risk of profound sedation, respiratory depression, and coma.
* **CYP2C19 Inhibitors/Inducers:** Clobazam is a substrate of CYP2C19. Fluconazole (inhibitor) may increase clobazam levels. Rifampin (inducer) may decrease clobazam levels.
* **Antiepileptic Drugs (AEDs):** Potential for additive CNS depression. Interactions with other AEDs may alter serum concentrations of either drug, requiring monitoring.
## Monitoring
* Seizure frequency and type.
* Signs of CNS depression (sedation, dizziness).
* Signs of withdrawal upon discontinuation.
* Signs of serious skin reactions.
* Liver function tests may be considered, especially with prolonged use or in patients with hepatic impairment.
## Clinical Pearls
* Clobazam has a longer half-life than many other benzodiazepines, allowing for less frequent dosing.
* Abrupt discontinuation can lead to withdrawal symptoms, including rebound seizures. Taper slowly when discontinuing.
* Due to the risk of serious skin reactions, patients should be advised to seek immediate medical attention if a rash develops.
* Clobazam is generally not recommended as monotherapy for epilepsy.
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*Please verify the current prescribing information for clobazam for complete details.*
