Disulfiram Chlordiazepoxide

Disulfiram inhibits hepatic drug metabolism and can prolong the effects of substances that are normally metabolized in the liver. This has been studied for various benzodiazepines. The clearances of chlordiazepoxide and diazepam were significantly reduced and their half-lives prolonged by disulfiram (43). 

Disulfiram and/or its metabolites can inhibit many enzymes with crucial sulfhydryl groups thus, disulfiram has a wide spectrum of biological effects. It inhibits hepatic CYPs and thereby mtetferes with the metabolism o/phenytoin, chlordiazepoxide, barbiturates, warfarin, and other drugs. 

An isolated report describes temazepam toxicity due to disulfiram. The serum levels of chlordiazepoxide and diazepam are increased by the use of disulfiram and some patients may possibly experience increased drowsiness. Alprazolam, oxazepam and lorazepam are either not affected, or only minimally affected, by disulfiram. 

After taking disulfiram 500 mg daily for 14 to 16 days, the plasma clearance of single doses of chlordiazepoxide and diazepam were reduced by 54% and 41%, respectively, and Ihe half-lives were increased by 84% and 37%, respectively. The plasma levels of chlordiazepoxide were approximately doubled. Oxazepam was also given following disulfiram treat-menl bul changes in oxazepam pharmacokinetics were minimal. There was no difference in Ihe interaction belween alcoholic subjects (without hepatic cirrhosis) and healthy subjects. ... 

Disulfiram inhibits the initial metabolism (A-demethylation and oxidation) of both chlordiazepoxide and diazepam by the liver so that an alternative but slower metabolic pathway is used. This results in the accumulation of these benzodiazepines in the body. In contrast, the metabolism (glucuronidation) of oxazepam and lorazepam is minimally affected by disulfiram so that their clearance from the body remains largely unaffected. The possible interaction between disulfiram and temazepam is not understood, as temazepam is also mainly eliminated in the urine as the inactive glucuronide metabolite, and so its metabolism would not be expected to be affected by disulfiram. 

There seems to be only one report (with temazepam) of a olinieally signif-ieant interaction between disiifiram and the benzodiazepines, and this report is unconfirmed, as the patient did not take temazepam alone. The other reports only describe potential interactions that have been identified by single-dose studies. These do not necessarily reliably predict what will happen in practice. However, it seems possible that some patients will experience increased drowsiness, possibly because of this interaction, and because drowsiness is a very common adverse effect of disulfiram. Reduce the dosage of the benzodiazepine if necessary. Benzodiazepines that are metabolised by similar pathways to diazepam and chlordiazepoxide, may possibly interact in the same way (e.g. bromazepam, clonazepam, clorazepate, prazepam, ketazolam, clobazam, flurazepam, nitrazepam, medazepam) but this needs confirmation. Alprazolam, oxazepam and lo-razepam appear to be non-interacting alternatives. 

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