clobazam: clinical use

Prescribing considerations

• Assess substance misuse, psychiatric illness, depression, suicidality and prescribed, non-prescribed and cannabidiol-containing products.
• Use caution in older or frail people and in renal, hepatic or respiratory impairment.
• Monitor for tolerance, loss of seizure control, misuse, dependence, paradoxical behavioural reactions and serious skin reactions.

Contraindications and cautions

• Hypersensitivity to clobazam, benzodiazepines or product excipients
• Myasthenia gravis
• Severe respiratory insufficiency
• Sleep apnoea syndrome
• Severe hepatic insufficiency
• History of drug or alcohol dependence, as specified in selected product information
• First trimester of pregnancy and breastfeeding, as specified in selected product licences
• Acute intoxication with alcohol or other centrally acting substances, for the selected oral-suspension product

Monitoring

• Sedation, cognition, coordination, falls and ability to drive safely
• Respiratory status when respiratory disease, opioids or other central nervous system depressants are present
• Seizure frequency, behavioural effects and evidence of tolerance
• Misuse, dependence and withdrawal symptoms
• Renal and hepatic function during long-term treatment
• Clinical response and, where appropriate, relevant medicine concentrations during interacting treatment

Clinical pharmacology

Clobazam is a 1,5-benzodiazepine that positively modulates GABA-A receptor activity. It is metabolised mainly by CYP3A4 to active N-desmethylclobazam, which is further metabolised primarily by CYP2C19. The long-lived metabolite contributes to accumulation, interactions and variability in CYP2C19 poor metabolisers.

Formulation and product differences

• Selected products include divisible tablets and oral suspensions with different concentrations and excipients.
• The tablet contains lactose and may be crushed into apple sauce; suspensions require thorough shaking and accurate measurement with the product-specific device.
• Tablet and suspension exposure may differ, so formulation changes require care and clinical review.
• Perizam contains maltitol, parabens, propylene glycol and sodium; Tapclob suspensions contain sorbitol and parabens.

Oral suspension

Route: Oral

Strengths: 1 mg/mL, 2 mg/mL, 5 mg/5 mL, 10 mg/5 mL

Tablet

Route: Oral

Strengths: 10 mg, 20 mg