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# Clobazam (Oral)
## Overview
Clobazam is a 1,5-benzodiazepine with a unique chemical structure that may provide a more favorable side-effect profile (e.g., less sedation) compared to 1,4-benzodiazepines. It acts as a positive allosteric modulator of the $\text{GABA}_A$ receptor.
## Primary Indications
Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥2 years old.
## Adult Dosing
* **Initial Dose:** 5 mg twice daily (10 mg/day).
* **Titration:** Increase at weekly intervals based on clinical response and tolerability.
* **Target/Maintenance Dose:** 20 mg twice daily (40 mg/day).
* **Note:** Doses >20 mg/day should be divided twice daily.
## Pediatric Dosing
* **Patients $\le$30 kg:**
* Initial: 5 mg once daily.
* Target: 20 mg/day (divided into two doses after 1 week).
* **Patients >30 kg:**
* Initial: 5 mg twice daily (10 mg/day).
* Target: 40 mg/day (divided into two doses after 1 week).
## Dose Adjustments
* **Renal Impairment:** No formal dosage adjustments provided; use caution as drug clearance may be prolonged.
* **Hepatic Impairment:** Reduce initial and target doses by 50%. Dose titration should be slower.
* **Geriatric:** Initiate at the lowest dose; titrate cautiously due to increased sensitivity to benzodiazepines.
* **CYP2C19 Poor Metabolizers:** Exposure to the active metabolite (N-desmethylclobazam) is increased 5-fold; initiate at 50% of the recommended dose and titrate cautiously.
## Contraindications
* Known hypersensitivity to clobazam.
* History of severe allergic reactions to any benzodiazepine.
## Adverse Effects
* **Common:** Somnolence, pyrexia, lethargy, drooling (sialorrhea), constipation, respiratory tract infection, ataxia, fatigue.
* **Serious:** Severe dermatological reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis—usually within the first 8 weeks), respiratory depression, suicidal ideation, and paradoxical reactions (aggression/irritability).
## Key Drug Interactions
* **CYP2C19 Inducers/Inhibitors:** Strong inhibitors (e.g., fluconazole, fluvoxamine) significantly increase clobazam metabolite levels.
* **CNS Depressants:** Concomitant use with opioids, alcohol, or other sedative-hypnotics increases the risk of profound sedation, respiratory depression, and death (Black Box Warning).
* **Hormonal Contraceptives:** Clobazam may decrease the efficacy of hormonal contraceptives; consider alternative non-hormonal methods.
* **AEDs:** May increase phenytoin levels; monitor for toxicity if added/removed.
## Monitoring
* Monitor for signs of respiratory depression and suicidal thoughts/behaviors.
* Screen for skin rash; discontinue immediately if a rash occurs unless it is clearly not drug-related.
* Monitor for worsening of seizure frequency when titrating or discontinuing.
## Clinical Pearls
* **Tapering:** Never discontinue abruptly; must be tapered gradually over 2+ weeks to prevent withdrawal seizures and status epilepticus.
* **Administration:** Oral suspension should be shaken well. Tablets can be crushed and mixed with applesauce.
* **Tolerance:** Tolerance to the anticonvulsant effects may develop over time, though clinical data on long-term efficacy remains debated.
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**Disclaimer:** This information is for educational purposes only. Clinical practice protocols may vary by institution. Always verify dosages and drug-drug interactions against current, authoritative resources (e.g., UpToDate, Lexicomp, or the manufacturer’s official package insert) before prescribing or administering medication.
