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# Clobazam (Oral)
## Overview
Clobazam is a benzodiazepine derivative used as an adjunctive treatment for seizures associated with Lennox-Gastaut syndrome (LGS). It is also used for other seizure types, particularly in pediatric patients.
## Primary Indications
* Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.
* Adjunctive treatment for other seizure types in pediatric patients (off-label in many regions, consult local guidelines).
## Adult Dosing
* **LGS:** The recommended starting dose is 5 mg orally twice daily. Increase dose by 5 mg/day every 3-7 days as needed. The usual maintenance dose is 10 mg twice daily. The maximum recommended dose is 20 mg twice daily.
* **Other Seizures (Off-label):** Dosing is highly variable and depends on seizure type and patient response. Consult specific protocols.
## Pediatric Dosing
* **LGS (2 to <10 years of age):** Starting dose 0.5 mg/kg/day divided into two doses. Increase dose by 0.5-1 mg/kg/day every 3-7 days. Maximum dose: 1 mg/kg/day divided into two doses, not to exceed the adult maximum of 20 mg twice daily.
* **LGS (10 to <30 kg):** Starting dose 5 mg orally once daily. Increase dose by 2.5-5 mg/day every 3-7 days. Maximum dose: 10 mg twice daily.
* **LGS (≥30 kg):** Starting dose 10 mg orally once daily. Increase dose by 5 mg/day every 3-7 days. Maximum dose: 20 mg twice daily.
* **Other Seizures (Off-label):** Dosing is highly variable and depends on seizure type and patient response. Consult specific protocols.
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. Consider lower doses.
* **Renal Impairment:** Use with caution. Consider lower doses.
* **Concomitant Medications:** Significant interactions exist (see Key Drug Interactions). Dose adjustments may be necessary.
## Contraindications
* Known hypersensitivity to clobazam or other benzodiazepines.
* Severe hepatic impairment.
## Adverse Effects
Common adverse effects include somnolence, decreased appetite, constipation, aggression, irritability, and behavioral changes. Serious adverse effects include serious skin reactions (e.g., Stevens-Johnson syndrome), suicidal ideation/behavior, respiratory depression, and physical dependence.
## Key Drug Interactions
* **CYP3A4 Inhibitors/Inducers:** Clobazam is metabolized by CYP3A4. Concomitant use with strong inhibitors (e.g., ketoconazole, ritonavir) can increase clobazam levels, while strong inducers (e.g., rifampin, carbamazepine) can decrease levels.
* **CYP2C19 Inhibitors:** Clobazam is a substrate of CYP2C19. Strong inhibitors (e.g., fluconazole) can increase clobazam levels.
* **CNS Depressants:** Additive sedative effects with alcohol, opioids, other benzodiazepines, antihistamines, and antipsychotics. Increased risk of respiratory depression.
* **Other Antiepileptic Drugs (AEDs):** Clobazam can affect levels of other AEDs (e.g., stiripentol, brivaracetam, valproic acid). Monitor AED levels and for toxicity.
## Monitoring
* Monitor for therapeutic effectiveness (seizure frequency).
* Monitor for adverse effects, particularly somnolence, behavioral changes, and signs of CNS depression.
* Monitor for signs of physical dependence and withdrawal symptoms upon discontinuation.
* Monitor for suicidal ideation and behavior.
* Monitor for serious skin reactions.
## Clinical Pearls
* Clobazam can be taken with or without food.
* Due to its long half-life, once-daily dosing may be possible for some patients, but twice-daily is standard for LGS.
* Withdrawal symptoms can occur upon abrupt discontinuation. Taper slowly.
* The risk of serious skin reactions is a significant concern; patients should be counseled to seek immediate medical attention if a rash develops.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and local protocols before making any treatment decisions.
