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# Clobazam (oral formulation)
## Overview
Clobazam is a benzodiazepine derivative with anticonvulsant properties. It is thought to exert its effects by enhancing the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
## Primary Indications
Adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.
## Adult Dosing
* **LGS:** The recommended starting dose is 5 mg twice daily.
* **Titration:** Increase dose by 2.5 mg to 5 mg every week as tolerated.
* **Maintenance:** Usual maintenance dose is between 0.5 mg/kg/day to 1 mg/kg/day, divided into two doses.
* **Maximum Dose:** Do not exceed 5 mg/kg/day or 600 mg daily, whichever is less.
## Pediatric Dosing (2 to 18 years)
* **LGS:** The recommended starting dose is 5 mg twice daily.
* **Titration:** Increase dose by 2.5 mg to 5 mg every week as tolerated.
* **Maintenance:** Usual maintenance dose is between 0.5 mg/kg/day to 1 mg/kg/day, divided into two doses.
* **Maximum Dose:** Do not exceed 5 mg/kg/day or 600 mg daily, whichever is less.
* **Note:** Dosing in younger children or those with lower body weight may require more precise adjustments. Local protocol may guide initial dosing and titration for this population.
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. No specific dose adjustment recommendations are established, but lower doses may be necessary.
* **Renal Impairment:** Use with caution. No specific dose adjustment recommendations are established, but lower doses may be necessary.
* **Concomitant Medications:** Dose reduction may be necessary when used with certain enzyme inhibitors (e.g., CYP2C19 inhibitors).
## Contraindications
* Known hypersensitivity to clobazam or other benzodiazepines.
* Severe hepatic impairment.
## Adverse Effects
Common adverse effects include somnolence, decreased appetite, aggression, irritability, constipation, vomiting, and falls. Serious adverse effects include increased seizure frequency or severity, suicidal behavior or ideation, severe skin reactions (e.g., Stevens-Johnson syndrome), and withdrawal symptoms.
## Key Drug Interactions
* **CYP2C19 Inhibitors (e.g., fluconazole, omeprazole):** May increase clobazam concentrations, potentially leading to increased adverse effects. Monitor closely and consider dose reduction of clobazam.
* **CYP2C19 Inducers (e.g., rifampin):** May decrease clobazam concentrations. Monitor for reduced efficacy.
* **CNS Depressants (e.g., alcohol, opioids, other sedatives):** Additive CNS depression may occur.
* **Other Anticonvulsants:** Monitor for potential changes in efficacy or adverse effects.
## Monitoring
* **Seizure frequency and severity:** Assess for efficacy and potential worsening of seizures.
* **Adverse effects:** Monitor for somnolence, behavioral changes, skin reactions, and signs of withdrawal.
* **Suicidal ideation/behavior:** Screen for these behaviors regularly.
* **Clobazam and N-desmethylclobazam (active metabolite) concentrations:** May be considered in cases of suspected toxicity, lack of efficacy, or significant drug interactions, though routine therapeutic drug monitoring is not typically required.
## Clinical Pearls
* Clobazam should be used as adjunctive therapy for LGS seizures.
* Due to the risk of serious skin reactions and suicidal behavior, patients and caregivers should be educated about these risks.
* Withdrawal symptoms can occur upon abrupt discontinuation. Tapering the dose gradually is recommended.
* Clobazam may cause cognitive impairment; caution patients regarding activities requiring mental alertness.
* Its active metabolite, N-desmethylclobazam, has a long half-life, contributing to prolonged effects and potential for accumulation.
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**Disclaimer:** This information is intended for healthcare professionals and does not replace the need to consult the most current prescribing information and available literature. Always verify current drug information with definitive sources.
