clomethiazole: clinical use

Prescribing considerations

• Alcohol withdrawal requires close hospital supervision; avoid outpatient use in people who continue to drink or misuse alcohol.
• Older people may have increased exposure and delayed elimination, increasing sedation risk.
• Use particular caution with sleep apnoea, chronic respiratory disease, significant hepatic impairment, chronic kidney disease or a history suggesting dependence or self-escalation.
• Review CNS depressants and relevant metabolic interactions before prescribing.
• Oral use is not recommended in children; safety and efficacy under 18 years have not been established.
• Sorbitol-containing formulations are unsuitable in hereditary fructose intolerance.

Contraindications and cautions

• Hypersensitivity to clomethiazole or formulation excipients
• Acute pulmonary insufficiency

Monitoring

• Consciousness and ability to remain rousable during alcohol withdrawal
• Respiratory and cardiovascular status
• Hepatic status
• Renal function where chronic kidney disease is present
• Tolerance, dependence, withdrawal or unsanctioned escalation
• Effects or concentrations of clinically important CYP2E1 substrates where appropriate

Clinical pharmacology

Clomethiazole is distinct from benzodiazepines and barbiturates and mainly potentiates GABA-A receptor activity. It has low oral bioavailability, high clearance, a short elimination half-life and extensive hepatic metabolism; elimination is slower in cirrhosis.

Formulation and product differences

• Capsules must be swallowed whole and stored in their original container, protected from light and moisture.
• Syrup must be diluted with water or juice and taken immediately; minimise plastic contact because of sorption.
• Syrup contains sorbitol and a small amount of ethanol. Refrigerate it, do not freeze it and keep it in its original bottle.
• Capsules also contain sorbitol but do not require refrigeration.

Capsule

Route: Oral

Strengths: 192 mg

Syrup

Route: Oral

Strengths: 31.5 mg/mL