What are the precautions and dosing guidelines for clobazam (benzodiazepine) therapy?

Clobazam Dosing and Precautions

Clobazam should be dosed according to patient weight, starting at 5-10 mg daily with gradual titration to minimize adverse effects, and requires special precautions for geriatric patients, CYP2C19 poor metabolizers, and those with hepatic impairment. 1

Dosing Guidelines

Standard Dosing by Weight

• ≤30 kg body weight:

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

• >30 kg body weight:

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

Administration

• Daily doses >5 mg should be administered in two divided doses
• 5 mg daily dose can be given as a single dose
• Can be taken with or without food 1
• For oral suspension: Shake well before administration and use only the provided oral dosing syringe 1

Special Population Dosing Adjustments

Geriatric Patients

• Start at 5 mg/day for all elderly patients
• Titrate to half the standard dose as tolerated
• If necessary, additional titration to maximum dose may begin on day 21 1

CYP2C19 Poor Metabolizers

• Start at 5 mg/day
• Titrate slowly to half the standard dose
• If needed, additional titration to maximum dose may begin on day 21 1

Hepatic Impairment

• Mild to moderate impairment (Child-Pugh 5-9):
  • Start at 5 mg/day regardless of weight
  • Titrate to half the standard dose
  • Additional titration to maximum dose may begin on day 21 1
• Severe hepatic impairment:
  • No dosing recommendations available due to inadequate information 1

Renal Impairment

• No dose adjustment required for mild to moderate renal impairment
• No experience with severe renal impairment or ESRD 1

Precautions and Warnings

Major Warnings

1. Risk with opioid use: Concomitant use with opioids may cause profound sedation, respiratory depression, coma, and death 1
2. Abuse, misuse, and addiction potential: Assess risk before prescribing and throughout treatment 1
3. Dependence and withdrawal: Use gradual taper when discontinuing (5-10 mg/day reduction weekly) 1

Common Adverse Effects

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

Serious Adverse Effects

• Respiratory depression (especially with other CNS depressants)
• Serious dermatological reactions (including Stevens-Johnson syndrome)
• Suicidal behavior and ideation 1
• Paradoxical agitation (occurs in about 10% of patients treated with benzodiazepines) 2

Drug Interactions

• Alcohol: Increases clobazam blood levels by approximately 50% 1
• CYP2D6 substrates: May require lower doses when used with clobazam 1
• Strong/moderate CYP2C19 inhibitors: May require clobazam dosage adjustment 1

Clinical Efficacy

• Effective as adjunctive therapy for Lennox-Gastaut syndrome (FDA-approved indication) 1, 3
• Shows efficacy in refractory partial epilepsy with 49.4% of patients achieving ≥50% seizure reduction 4
• In temporal lobe epilepsy with hippocampal sclerosis, 56% of patients showed >50% improvement in seizure control 5

Discontinuation

• To reduce withdrawal reactions, seizure frequency increases, and status epilepticus:
  • Decrease total daily dose by 5-10 mg/day weekly
  • If withdrawal reactions occur, pause taper or return to previous dose
  • Subsequently decrease dosage more slowly 1

Monitoring

• Assess for signs of CNS depression
• Monitor for respiratory depression, especially when combined with other CNS depressants
• Watch for dermatological reactions (discontinue at first sign of rash unless clearly not drug-related)
• Monitor for suicidal thoughts or behaviors 1