Clobazam Treatment Regimen for Epilepsy
Clobazam should be initiated at 5 mg daily for patients ≤30 kg or 10 mg daily for patients >30 kg, administered in divided doses if above 5 mg/day, with weekly titration to target doses of 20 mg/day (≤30 kg) or 40 mg/day (>30 kg) based on efficacy and tolerability. 1
Weight-Based Dosing Protocol
The FDA-approved dosing regimen follows a structured escalation schedule 1:
For patients ≤30 kg:
- Day 1: Start 5 mg once daily 1
- Day 7: Increase to 10 mg/day in divided doses 1
- Day 14: Increase to 20 mg/day in divided doses 1
For patients >30 kg:
- Day 1: Start 10 mg/day in divided doses 1
- Day 7: Increase to 20 mg/day in divided doses 1
- Day 14: Increase to 40 mg/day in divided doses 1
Critical Timing Considerations
Do not escalate doses more rapidly than weekly intervals, as clobazam requires 5 days to reach steady-state and its active metabolite N-desmethylclobazam requires 9 days 1. Premature dose escalation increases the risk of adverse effects without additional therapeutic benefit.
Administration Guidelines
- Doses >5 mg/day must be divided into twice-daily administration 1
- A 5 mg daily dose can be given as a single dose 1
- Can be taken with or without food 1
- Shake oral suspension well before each dose and use only the provided oral dosing syringe 1
Special Population Adjustments
Elderly patients require modified dosing:
- Start all elderly patients at 5 mg/day regardless of weight 1
- Titrate to half the standard doses shown in the weight-based table 1
- If needed, may increase to maximum dose (20 or 40 mg/day based on weight) starting day 21 1
CYP2C19 poor metabolizers require the same conservative approach:
- Start at 5 mg/day 1
- Titrate to half the standard doses 1
- Optional escalation to maximum dose starting day 21 if clinically indicated 1
Hepatic impairment:
- Proceed slowly with dose escalation due to hepatic metabolism 1
- No specific dosing recommendations available for severe hepatic impairment 1
Renal impairment:
- No dose adjustment needed for mild-to-moderate renal impairment 1
- No data available for severe renal impairment or end-stage renal disease 1
Discontinuation Protocol
Never abruptly discontinue clobazam due to risks of withdrawal reactions, increased seizure frequency, and status epilepticus 1.
Gradual taper protocol:
- Decrease total daily dose by 5-10 mg/day on a weekly basis until discontinued 1
- If withdrawal reactions develop, pause the taper or increase back to the previous dose level 1
- Subsequently decrease more slowly 1
Clinical Efficacy Context
Research demonstrates that clobazam produces seizure freedom in 7-20% of patients with refractory epilepsy and >50% seizure reduction in approximately 50-65% of patients when used as adjunctive therapy 2, 3, 4. The typical effective dose range in clinical studies was 20-40 mg/day (mean 22-37 mg/day) 2, 3, 4. Efficacy tolerance has not been a significant problem in well-designed studies, though approximately 36% of patients may develop tolerance over time 5, 6.
Critical Safety Warnings
Boxed warnings mandate attention to:
- Concomitant opioid use: Reserve only for patients without alternatives; limit dosages and durations; monitor for respiratory depression 1
- Abuse and addiction risk: Assess each patient's risk before prescribing and throughout treatment 1
- Physical dependence: Develops with continued use; abrupt discontinuation can precipitate life-threatening withdrawal 1
Common adverse effects include sedation (most frequent), constipation, pyrexia, lethargy, and drooling, occurring in >10% of patients 1. Serious dermatological reactions including Stevens-Johnson syndrome require immediate discontinuation at first sign of rash 1.