Clobazam Dosing in Children
For pediatric patients with epilepsy, initiate clobazam at 5 mg/day for children ≤30 kg or 10 mg/day for children >30 kg, then titrate weekly to a target maintenance dose of 20 mg/day (≤30 kg) or 40 mg/day (>30 kg), administered in divided doses twice daily. 1
Weight-Based Dosing Algorithm
Children ≤30 kg Body Weight
- Starting dose (Day 1): 5 mg/day (can be given as single daily dose) 1
- Day 7: Increase to 10 mg/day (divided twice daily) 1
- Day 14: Increase to 20 mg/day (divided twice daily) 1
- Maximum dose: 20 mg/day 1
Children >30 kg Body Weight
- Starting dose (Day 1): 10 mg/day (divided twice daily) 1
- Day 7: Increase to 20 mg/day (divided twice daily) 1
- Day 14: Increase to 40 mg/day (divided twice daily) 1
- Maximum dose: 40 mg/day 1
Critical Dosing Principles
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.
Any daily dose greater than 5 mg must be divided into twice-daily administration to optimize tolerability and maintain stable plasma concentrations. 1
Practical Dosing Considerations
Real-world pediatric epilepsy studies demonstrate that the typical effective dose range is 0.2-0.8 mg/kg/day, with a median target dose of approximately 0.48 mg/kg/day. 2 However, the FDA-approved weight-based dosing table should guide initial prescribing rather than mg/kg calculations, as this approach has been validated in clinical trials. 1
Research shows that 67.7% of children with refractory epilepsy respond to clobazam (≥50% seizure reduction), with 28% achieving complete seizure freedom. 2 Response rates are dose-dependent, with higher doses within the approved range showing greater efficacy. 1
Special Population Adjustments
CYP2C19 Poor Metabolizers
For children identified as CYP2C19 poor metabolizers, start at 5 mg/day regardless of weight, then titrate to half the standard doses (10 mg/day for ≤30 kg or 20 mg/day for >30 kg by Day 14). 1 These patients accumulate higher levels of the active metabolite N-desmethylclobazam, requiring dose reduction to prevent toxicity. 1
If necessary based on clinical response and tolerability, further titration to maximum doses (20 mg/day or 40 mg/day) may begin on Day 21. 1
Administration Guidelines
Clobazam oral suspension can be administered with or without food. 1 Always shake the suspension well before each dose and use only the provided oral dosing syringe for accurate measurement. 1 Slowly withdraw the prescribed dose, then administer by slowly squirting into the corner of the patient's mouth. 1
Safety Profile and Monitoring
The most common adverse effects in pediatric patients are tiredness (14.6%) and mood or behavioral changes (7.7%). 2 Only 9% of children discontinue clobazam, with 59.3% of discontinuations due to adverse effects. 2
Clobazam demonstrates superior tolerability compared to other benzodiazepines because it preferentially binds to GABA-A receptor subunits that mediate anticonvulsant effects rather than sedative effects. 3 The active metabolite N-desmethylclobazam contributes to the prolonged therapeutic effect, with an elimination half-life of 40-50 hours compared to 18 hours for the parent drug. 4
Discontinuation Protocol
Never abruptly discontinue clobazam due to risk of withdrawal seizures and status epilepticus. 1 Taper by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued. 1 If withdrawal symptoms develop, pause the taper or increase back to the previous dose level, then resume tapering more slowly. 1
Common Pitfalls to Avoid
- Avoid rapid dose escalation: Weekly titration is mandatory to allow steady-state achievement and minimize adverse effects. 1
- Avoid single daily dosing for doses >5 mg: Divided twice-daily dosing is required for optimal tolerability. 1
- Avoid using mg/kg dosing as primary guide: The weight-based dosing table provides validated, safe escalation schedules. 1
- Avoid overlooking CYP2C19 status: Poor metabolizers require 50% dose reduction to prevent metabolite accumulation. 1