Please check your internet connection and try again.
# Clobazam (Oral Formulation)
## Overview
Clobazam is a 1,5-benzodiazepine with anticonvulsant properties. Unlike 1,4-benzodiazepines (e.g., diazepam), it has a partial agonist profile at the GABA-A receptor, which may result in a more favorable side effect profile regarding sedation and tolerance. It is a controlled substance (Schedule IV).
## Primary Indications
Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥2 years.
## Adult Dosing
* **Initial Dose:** 5 mg twice daily (10 mg/day total).
* **Titration:** Increase gradually every 7 days based on clinical response and tolerance to 10 mg twice daily (20 mg/day total), then 20 mg twice daily (40 mg/day total).
* **Target/Maximum Dose:** 40 mg/day (given in two divided doses).
## Pediatric Dosing (≥2 years)
Dosing is weight-based.
* **Patients ≤30 kg:**
* Initial: 5 mg/day.
* Titration: After 7 days, increase to 10 mg/day.
* Maximum: 20 mg/day.
* **Patients >30 kg:**
* Initial: 5 mg twice daily (10 mg/day total).
* Titration: Increase every 7 days to 20 mg/day, then 40 mg/day.
* Maximum: 40 mg/day.
## Dose Adjustments
* **Hepatic Impairment:** Reduce starting dose by 50%; titrate slowly. Avoid in severe impairment (Child-Pugh Class C).
* **Renal Impairment:** No specific adjustment guidelines, but use caution as some metabolites are renally excreted.
* **CYP2C19 Poor Metabolizers:** Monitor closely; these patients may experience higher plasma levels of the active metabolite (N-desmethylclobazam).
## Contraindications
Hypersensitivity to clobazam or any component of the formulation.
## Adverse Effects
* **Common:** Somnolence, sedation, lethargy, pyrexia, drooling, constipation, upper respiratory tract infections, aggression/irritability.
* **Serious:** Severe dermatological reactions (Stevens-Johnson syndrome, Toxic Epidermal Necrolysis), respiratory depression, suicidal ideation, paradoxical reactions.
## Key Drug Interactions
* **CNS Depressants:** Enhanced sedative effects (alcohol, opioids, other benzodiazepines).
* **CYP2C19 Inhibitors:** (e.g., fluconazole, fluvoxamine, omeprazole) Increase levels of the active metabolite.
* **CYP2D6 Substrates:** Clobazam may increase levels of drugs like dextromethorphan or paroxetine.
* **Hormonal Contraceptives:** May decrease efficacy (clobazam is a weak inducer of CYP3A4).
## Monitoring
* **Respiratory Status:** Especially when combined with opioids.
* **Dermatology:** Educate patients/caregivers to monitor for rash, particularly in the first 8 weeks of therapy; discontinue immediately if SJS/TEN is suspected.
* **Behavioral/Mood:** Monitor for signs of worsening depression or suicidal ideation.
* **Seizure Activity:** Monitor frequency and severity to assess clinical response.
## Clinical Pearls
* **Withdrawal:** Abrupt discontinuation can trigger status epilepticus. Taper the dose gradually when discontinuing.
* **Administration:** Tablets can be swallowed whole or crushed and mixed with applesauce/yogurt. Oral suspension must be shaken well before use.
* **Tolerance:** Tolerance to the anticonvulsant effects may develop over time, though it is often less pronounced than with other benzodiazepines.
* **N-desmethylclobazam:** The active metabolite has a significantly longer half-life (up to 40–50 hours) than the parent drug, contributing to sustained effects.
***
**Educational Disclaimer:** This information is for educational purposes only. Always consult the most current official prescribing information (package insert) and local institutional protocols before prescribing or administering any medication.
