Clomethiazole Alcohol

Nimmerrichter AA, Walter H, Gutierrez-Lobos KE, et al Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal. Alcohol 37 67—73, 2002... 

Clomethiazole can also be effective for controlling status epilepticus but is used mainly to treat agitated states, especially alcoholic delirium tremens and associated seizures. 

The functional capacity of the brain is impaired. Irreversible damage may manifest in a measurable fallout of neuronal cell bodies. Often delirium tremens develops (usually triggered by alcohol withdrawal), which can be managed with intensive therapy (clomethiazole, haloperidol, among others). In addition, alcoholic hallucinations and Wernicke-Korsakow syndrome occur. All of these are desolate states. 

A 53-year-old male car driver was followed by the police for about 2 km, while he drove in an unsafe manner, until the car crashed into the owner s garage. Analysis of his blood showed a clomethiazole concentration of 3.3 pg/ml. Neither alcohol nor any other drug could be detected. One day later he committed suicide by swallowing at least 60 capsules of clomethiazole. 

Clomethiazole is structurally related to vitamin B 1 (thiamine) and is a hypnotic, sedative and anticonvulsant. It is comparatively free from hangover it can cause nasal irritation and sneezing. Dependence occurs and use should always be brief. When taken orally, it is subject to extensive hepatic first-pass metabolism (which is defective in the elderly and in liver damaged alcoholics who get higher peak plasma concentrations), and the usual t) is 4 h (with more variation in the old than the young) it may also be given i.v. 

Clomethiazole was an alternative to a benzodiazepine for alcohol withdrawal but is now rarely used due to concerns over respiratory depression and abuse potential. 

When treating alcoholic liver diseases, it should be taken into account that one is generally dealing with chronic alcoholics. Therefore, one should be aware of the fact that a withrawal syndrome might occur, possibly requiring the application of clomethiazole, haloperidol or clonidine. In this complicated phase, the administration of zinc is likewise recommended. (138)... 

Medium-chain triglycerides solubilize 192 mg of clomethizole edisilate in Heminevrin Capsules soft gelatin capsules (60 mg equivalent of clomethiazole). Clomethiazole is an oily viscous liquid as the free base but the edisilate (ethanedisulfonate) salt is a solid. Clomethiazole is a short-acting hypnotic and sedative with anticonvulsant effects, and Heminevrin is indicated for treatment of resdessness and insomnia that accompany alcohol withdrawal. Clomethiazole has a short half-life and low bioavailability due to extensive hepatic hrst-pass metabolism. The dose of Heminevrin is one to four capsules as needed, and the capsules are stored at room temperature. Heminevrin Capsules have been available in the United Kingdom since 1998. 

Clomethiazole has been successfully used to treat alcohol withdrawal, but the long-term use of alcohol with clomethiazole can cause serious, even potentially fatal CNS depression, due to additive CNS depressant effects fatal respiratory depression can occur even with short-term use in alcoholics with cirrhosis. The concurrent use of clomethiazole and alcohol may also affect driving skills. Clomethiazole bioavailability may be increased by alcohol. 

Clomethiazole is commonly used to treat withdrawal from alcohol because of its hypnotic, anxiolytic and anticonvulsant effects. It is very effective if a rapidly reducing dosage regimen is followed over six days, but if it is used long-term and drinking continues it carries several serious risks. 

Alcoholics readily transfer dependency to clomethiazole and may visit several practitioners and hospitals to get their supplies. Tolerance develops so that very large amounts may need to be taken (up to 25 g daily). Often alcohol abuse continues and the combination of large amounts of alcohol and clomethiazole can result in coma and even fatal respiratory depression, due mainly to simple additive CNS depression. ... 

Other factors are that aleohol inereases the bioavailability of clomethiazole (probably by impairing first pass metabolism), and in the case of those with alcoholic cirrhosis, the systemic bioavailability may be increased tenfold because of venous shunting. However, one study in 6 healthy subjects reported that intravenous alcohol 0.8 mL/kg given acutely had no effect on the disposition or elimination of clomethiazole. It was proposed that alcohol given orally might affect the absorption or rate of uptake of clomethiazole. ... 

Clomethiazole should not be given long-term for alcohol withdrawal states or to those who continue to drink alcohol. Use for more than 9 days is not recommended. It has been said that if prescribers choose to manage detoxification at home, it should be done under very close supervision, issuing prescriptions for only one day s supply to ensure daily contact and to minimise tiie risk of abuse. And if the patient shows evidence of tolerance or clomethiazole dependency or of continuing to drink alcohol, the only safe policy is rapid admission for inpatient care. The manufacturer warns that alcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short-term use. ... 

There do not appear to be any studies on the combined effects of clomethiazole and alcohol on driving and related skills, but concurrent use would be expected to increase the risks. 

Gabapentin 800 mg on the first day and 600 mg/day on the next 2 days has been prospectively studied in the treatment of acute severe alcohol withdrawal symptoms in 37 patients, of whom 27 were early responders and 10 required treatment with clomethiazole ( = 4) or clonazepam... 

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