Clobazam Dosing in Pediatric Patients
For pediatric patients ≥2 years old with Lennox-Gastaut syndrome, start clobazam at 5 mg/day for patients ≤30 kg or 10 mg/day for patients >30 kg, titrating weekly to target doses of 20 mg/day (≤30 kg) or 40 mg/day (>30 kg) based on efficacy and tolerability. 1
Weight-Based Dosing Algorithm
Patients ≤30 kg Body Weight
- Starting dose: 5 mg/day (can be given as single daily dose) 1
- Day 7: Increase to 10 mg/day (divide into twice daily dosing) 1
- Day 14: Increase to 20 mg/day (divide into twice daily dosing) 1
Patients >30 kg Body Weight
- Starting dose: 10 mg/day (divide into twice daily dosing) 1
- Day 7: Increase to 20 mg/day (divide into twice daily dosing) 1
- Day 14: Increase to 40 mg/day (divide into twice daily dosing) 1
Critical Dosing Principles
Weekly titration only: Do not escalate doses more rapidly than weekly intervals, as clobazam requires 5 days and its active metabolite N-desmethylclobazam requires 9 days to reach steady-state concentrations 1
Divided dosing requirement: Any daily dose >5 mg must be administered in two divided doses; only the 5 mg daily dose can be given as a single dose 1
Dose-response relationship: Each dose level within the weight-based ranges has demonstrated efficacy, with effectiveness increasing at higher doses 1
Real-World Dosing Experience
Research data from tertiary pediatric centers shows broader dosing ranges are commonly used in clinical practice:
- Typical starting dose: 0.2 mg/kg/day (range 0.13-0.33 mg/kg/day) 2
- Target maintenance dose: 0.48 mg/kg/day (range 0.26-0.80 mg/kg/day) 2
- Absolute dose range: 5-60 mg/day (mean 37.5 mg/day) in epileptic encephalopathies 3
These real-world doses often exceed FDA-labeled recommendations but demonstrate that 67.7% of pediatric patients with refractory epilepsy achieve ≥50% seizure reduction, with 28% becoming seizure-free 2
Special Populations Requiring Dose Adjustment
CYP2C19 Poor Metabolizers
- Starting dose: 5 mg/day for all patients regardless of weight 1
- Titration: Proceed to half the standard doses in Table 1 based on weight and tolerability 1
- Rationale: These patients accumulate higher levels of the active metabolite N-desmethylclobazam 1
Discontinuation Protocol
To prevent withdrawal seizures and status epilepticus, taper clobazam by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued. 1
- If withdrawal reactions occur, pause the taper or increase back to the previous dose level, then resume tapering more slowly 1
- Abrupt discontinuation can precipitate life-threatening withdrawal reactions 1
Safety Monitoring
Common Adverse Effects
- Tiredness: Occurs in 14.6% of pediatric patients 2
- Mood/behavioral changes: Occurs in 7.7% of pediatric patients 2
- Discontinuation rate: Only 9% of patients discontinue due to adverse effects or lack of efficacy 2
Critical Drug Interactions
- Valproic acid: Clobazam significantly reduces valproate clearance; monitor valproate levels closely and watch for toxicity 4
- Primidone: Clearance is reduced with clobazam cotherapy 4
- Phenobarbital: Decreases clobazam serum concentrations 4
- Phenytoin/Carbamazepine: Increase N-desmethylclobazam concentrations 4
Black Box Warnings
- Concomitant opioid use: Reserve only for patients without alternative options; can cause profound sedation, respiratory depression, coma, and death 1
- Abuse potential: Assess each patient's risk for abuse, misuse, and addiction before prescribing and throughout treatment 1
- Physical dependence: Develops with continued use; requires gradual taper to discontinue 1
Efficacy Across Epilepsy Syndromes
While FDA-approved only for Lennox-Gastaut syndrome in patients ≥2 years, clobazam demonstrates efficacy across multiple pediatric epilepsy syndromes including myoclonic astatic epilepsy and West syndrome, with 85% of responders maintaining improvement for >1 year 3. The drug is well-tolerated with a high safety profile and minimal development of efficacy tolerance in well-designed studies 5