Clomethiazole

Oral

Insomnia

Adult: 1 or 2 capsules (192 or 384 mg of the base or the equivalent) before going to bed.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Oral

Alcohol withdrawal syndrome

Adult: Per cap contains 192 mg Clomethiazole base. On the 1st day, 9-12 capsules, or the equivalent, divided into 3 or 4 doses. Gradually reduce dosage over the following 5 days. Not to be used for >9 days.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Oral

Sedation

Adult: 1 capsule (192 mg of the base or the equivalent) tid.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Intravenous

Status epilepticus

Adult: Initially, 5-15 ml/min (0.8% solution) infusion, up to a total of 40-100 ml. Reduce thereafter to a slower maintenance rate depending on the patient's response (usual rate: 0.5-1 ml/min).

Child: Initially, 0.01 mL/kg/min (0.8% solution) infusion, gradually adjust upwards every 2-4 hr until seizures stop or drowsiness occurs. Reduce gradually every 4-6 hr once seizures have been absent for about 2 days.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Intravenous

Alcohol withdrawal syndrome

Adult: Initially, 3-7.5 ml/min (0.8% solution) infusion until shallow sleep is induced, reduce thereafter to 0.5-1 ml/min to maintain shallow sleep and adequate spontaneous breathing. For urgent deep sedation: Initially, 40-100 ml of a 0.8% solution may be given over 3-5 min.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Intravenous

Pre-eclamptic toxaemia

Adult: Initially, 0.5-0.75 ml/min (0.8% solution) infusion during labour. Maintain at 0.5 ml/min for 12 hr following delivery. May continue with oral therapy thereafter.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Oral

Insomnia

Adult: 1 or 2 capsules (192 or 384 mg of the base or the equivalent) before going to bed.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Oral

Alcohol withdrawal syndrome

Adult: Per cap contains 192 mg Clomethiazole base. On the 1st day, 9-12 capsules, or the equivalent, divided into 3 or 4 doses. Gradually reduce dosage over the following 5 days. Not to be used for >9 days.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Oral

Sedation

Adult: 1 capsule (192 mg of the base or the equivalent) tid.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Intravenous

Status epilepticus

Adult: Initially, 5-15 ml/min (0.8% solution) infusion, up to a total of 40-100 ml. Reduce thereafter to a slower maintenance rate depending on the patient's response (usual rate: 0.5-1 ml/min).

Child: Initially, 0.01 mL/kg/min (0.8% solution) infusion, gradually adjust upwards every 2-4 hr until seizures stop or drowsiness occurs. Reduce gradually every 4-6 hr once seizures have been absent for about 2 days.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Intravenous

Alcohol withdrawal syndrome

Adult: Initially, 3-7.5 ml/min (0.8% solution) infusion until shallow sleep is induced, reduce thereafter to 0.5-1 ml/min to maintain shallow sleep and adequate spontaneous breathing. For urgent deep sedation: Initially, 40-100 ml of a 0.8% solution may be given over 3-5 min.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Intravenous

Pre-eclamptic toxaemia

Adult: Initially, 0.5-0.75 ml/min (0.8% solution) infusion during labour. Maintain at 0.5 ml/min for 12 hr following delivery. May continue with oral therapy thereafter.

Renal impairment: Dose reduction may be needed.

Hepatic impairment: Dose reduction may be needed.

Known sensitivity to Clomethiazole. Acute pulmonary insufficiency.

A combination of Clomethiazole and diazoxide should be avoided as an adverse neonatal reaction suspected to be due to the maternal administration of this combination has been reported.

The combination of propranolol and Clomethiazole has produced profound bradycardia in one patient possibly due to increased bioavailability of propranolol.

There is evidence to indicate that the metabolism of Clomethiazole is inhibited by cimetidine, thus the co-administration of these drugs may lead to increased blood/plasma levels of Clomethiazole.

When Clomethiazole was administered by intravenous infusion in combination with carbamazepine, the clearance of Clomethiazole increased by 30%, resulting in decreased plasma concentrations to the same extent. This interaction has not been studied after oral administration of Clomethiazole. However, co-administration of carbamazepine and oral Clomethiazole could result in both decreased bioavailability and increased clearance. Higher doses of Clomethiazole could therefore be needed to obtain an effect when co-administered with carbamazepine or another potent inducer of the CYP3A4 enzyme

The most common side-effect is nasal congestion and irritation, which may occur 15 to 20 minutes after drug ingestion. Conjunctival irritation has also been noted in some cases. Occasionally, these symptoms may be severe and may be associated with severe headache. This is commonest with the initial dose following which it decreases in severity with subsequent doses. Increased nasopharyngeal/bronchial secretions can occur.

Rash and urticaria have been reported. In rare cases, bullous skin eruptions have been reported.

Gastrointestinal disturbances have been reported.

Reversible increases of transaminases or bilirubin have been reported.

In rare cases anaphylactic reactions have occurred.

When Clomethiazole has been given at higher than recommended doses for other than recommended indications over prolonged periods of time, physical dependence, tolerance and withdrawal reactions have been reported.

Great caution is required in prescribing Clomethiazole for patients with a history of chronic alcoholism, drug abuse or marked personality disorder.

When used as a night-time hypnotic, hangover effects in the elderly may occur but are uncommon due to the short half-life.

Excessive sedation may occur, especially with higher doses or when given to the elderly for daytime sedation. Paradoxical excitement or confusion may occur rarely.