Are there any known interactions between clomethiazole and diazepam?

Fråga: Are there any known interactions between clomethiazole and diazepam? Colleagues of the questioner have heard that the combination has been banned in Hungary due to cases of cardiac arrest in patients treated with clomethiazole and diazepam.

Sammanfattning: There are no known pharmacokinetic interactions between chlomethiazole and diazepam. A few older case reports have suspected a link between cardiac arrest and chlomethiazole treatment, but causality has not been confirmed. However, both chlomethiazole and diazepam are CNS-depressant and their effects may be enhanced by concomitant treatment.

Svar: Clomethiazole is an antispasmodic, sedative used for treatment of delirium tremens, pre delirious conditions and withdrawal symptoms after alcohol abuse, as well as for sleep disturbances and agitation in geriatric medicine (1). Diazepam is a benzodiazepine used as anxiolytic, muscle relaxant, antispasmodic, calming and sedating agent (2).

Searches in the Sphinx interaction database, Stockley´s Drug Interactions and on PubMed no known pharmacokinetic interactions can be found (3,4). However, chlomethiazole effects can be enhanced by other CNS depressants - including alcohol and benzodiazepines, or can enhances the effect of such drugs (1,4).

An extended literature search does not reveal any further studies or case reports on interactions between chlomethiazole and diazepam. A specific search of cardiac arrest and/or cardiac disease in combination with the two drugs yields nothing. However, a search for chlomethiazole and cardiac arrest reveals one paper. This is a Scottish report from 1980 which describes two cases of cardiac arrest after alcohol withdrawal treatment with i.v. infusion of chlomethiazole. Both patients also received i.v. infusions of diazepam. The authors could not establish causality (5). However, the SPC for Hemineurin, lists among the known adverse reactions (frequency not specified) "Cardiac arrest, usually associated with respiratory depression, especially at high doses and concomitant use of other CNS depressants" (1). No such events have been reported to the Swedish adverse effect registry (6).