What is the recommended dose of Frisium (clobazam) for a pediatric patient?

Frisium (Clobazam) Dosing in Pediatric Patients

For children ≥2 years old with Lennox-Gastaut syndrome, start clobazam at 5 mg daily for patients ≤30 kg or 10 mg daily for patients >30 kg, then titrate weekly to target doses of 20 mg/day and 40 mg/day respectively, divided into twice-daily administration for doses above 5 mg. 1

Weight-Based Dosing Algorithm

The FDA-approved dosing follows a structured three-week titration schedule based on body weight 1:

For Children ≤30 kg:

• Week 1 (Days 1-6): 5 mg once daily 1
• Week 2 (Days 7-13): 10 mg divided twice daily 1
• Week 3 onward (Day 14+): 20 mg divided twice daily 1

For Children >30 kg:

• Week 1 (Days 1-6): 10 mg divided twice daily 1
• Week 2 (Days 7-13): 20 mg divided twice daily 1
• Week 3 onward (Day 14+): 40 mg divided twice daily 1

Critical Titration Considerations

Do not escalate doses more rapidly than weekly intervals because 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 accumulation and adverse effects.

The dose range within each weight category (5-20 mg for ≤30 kg; 10-40 mg for >30 kg) has demonstrated efficacy, with effectiveness increasing at higher doses, allowing individualization based on clinical response and tolerability 1.

Administration Guidelines

• Doses >5 mg/day must be divided into twice-daily administration 1
• Single daily dosing is acceptable only for the 5 mg dose 1
• Shake the oral suspension well before each dose 1
• Use only the provided oral dosing syringe for accurate measurement 1
• Can be administered with or without food 1

Special Population Adjustments

CYP2C19 Poor Metabolizers:

These patients accumulate higher levels of the active metabolite N-desmethylclobazam 1. For known poor metabolizers:

• Start at 5 mg/day regardless of weight 1
• Titrate to half the standard doses in Table 1 (i.e., maximum 10 mg/day for ≤30 kg; 20 mg/day for >30 kg) 1

Discontinuation Protocol

Never abruptly stop clobazam due to risks of withdrawal reactions, increased seizure frequency, and status epilepticus 1. Use a gradual taper:

• Decrease total daily dose by 5-10 mg/week until discontinued 1
• If withdrawal symptoms emerge, pause the taper or increase back to the previous dose level, then taper more slowly 1

Safety Monitoring

The most serious risks include 1:

• Respiratory depression (especially with concomitant opioids—reserve combination only when alternatives are inadequate) 1
• Abuse, misuse, and addiction potential (assess risk before and during treatment) 1
• Physical dependence with prolonged use 1
• Serious dermatological reactions including Stevens-Johnson syndrome—discontinue at first sign of rash unless clearly unrelated 1
• Somnolence and sedation—monitor for CNS depression, particularly with other CNS depressants 1
• Suicidal behavior and ideation—monitor for emergence of suicidal thoughts 1

Common Pitfalls to Avoid

• Do not use adult dosing in children—pediatric patients require weight-based mg/kg calculations, not simply reduced adult doses 2, 3
• Do not skip the weekly titration intervals—premature escalation before steady-state is reached increases toxicity risk 1
• Do not administer doses >5 mg once daily—divided dosing is required for efficacy and tolerability 1
• Do not use standard dosing in CYP2C19 poor metabolizers—these patients require 50% dose reduction 1