What is the recommended dosage and usage of Clobazam for anxiety disorders and epilepsy management?

Clobazam Dosage and Usage for Anxiety Disorders and Epilepsy Management

For epilepsy management, clobazam is dosed according to body weight: patients ≤30 kg should start at 5 mg daily and titrate up to 20 mg daily, while patients >30 kg should start at 10 mg daily and titrate up to 40 mg daily, with dose escalation occurring no more rapidly than weekly. 1

Dosing for Epilepsy (Lennox-Gastaut Syndrome)

Weight-Based Dosing

• For patients ≤30 kg:

  • Starting dose: 5 mg daily 1
  • Day 7: Increase to 10 mg daily 1
  • Day 14: Increase to 20 mg daily (maximum dose) 1

• For patients >30 kg:

  • Starting dose: 10 mg daily 1
  • Day 7: Increase to 20 mg daily 1
  • Day 14: Increase to 40 mg daily (maximum dose) 1

Administration Guidelines

• Daily doses >5 mg should be administered in divided doses twice daily 1
• A 5 mg daily dose can be administered as a single dose 1
• Clobazam can be taken with or without food 1
• Do not escalate doses more rapidly than weekly, as clobazam and its active metabolite require 5 and 9 days, respectively, to reach steady-state 1

Special Populations

Elderly Patients

• Starting dose: 5 mg/day for all elderly patients 1
• Titrate according to weight, but to half the standard dose as tolerated 1
• If necessary, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on weight) may be started on day 21 1

CYP2C19 Poor Metabolizers

• Starting dose: 5 mg/day 1
• Titrate slowly according to weight, but to half the standard dose as tolerated 1
• If necessary, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on weight) may be started on day 21 1

Renal Impairment

• No dose adjustment required for mild to moderate renal impairment 1
• Limited data available for severe renal impairment or end-stage renal disease 1

Hepatic Impairment

• Proceed slowly with dose escalation in patients with hepatic impairment 1

Use in Anxiety Disorders

While clobazam is primarily indicated for epilepsy in the US (specifically Lennox-Gastaut syndrome), it has been used internationally for anxiety disorders:

• Typical dosage for anxiety: 20-30 mg/day 2
• Can be administered as either a single daily dose or divided doses 3, 4
• Studies have shown that single daily dosing (20 mg at night) is as effective as divided dosing (10 mg twice daily) for anxiety 3, 4

Important Safety Considerations

Risks and Warnings

• Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death 1
• Risk of abuse, misuse, and addiction 1
• Abrupt discontinuation may precipitate withdrawal reactions 1

Discontinuation Protocol

• Use a gradual taper to discontinue clobazam or reduce the dosage 1
• Taper by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued 1
• If withdrawal reactions occur, consider pausing the taper or increasing to the previous dosage level, then decrease more slowly 1

Common Side Effects

• Somnolence or sedation 1
• Constipation 1
• Pyrexia 1
• Lethargy 1
• Drooling 1

Clinical Efficacy

• In refractory epilepsy, clobazam has shown >50% reduction in seizure frequency in 40-50% of patients 5
• Complete seizure freedom (100% reduction) has been reported in 10-30% of patients 5
• Tolerance leading to discontinuation occurs in approximately 9% of patients 5
• Clobazam has demonstrated efficacy as both adjunctive therapy and in limited monotherapy trials 6

Clobazam's unique 1,5-benzodiazepine structure results in less sedation compared to other benzodiazepines, making it valuable for both epilepsy management and anxiety treatment when appropriate 6.