An isolated report describes temazepam toxicity due to disulfiram. The serum levels of chlordiazepoxide and diazepam areincreased by use of disulfiram and some patients may possiblyexperience increased drowsiness. Alprazolam,oxazepam and lorazepam are either not affected, or only minimally affected, by disulfiram.
A man taking disulfiram 200mg daily developed confusion,drowsiness, slurred speech and an unsteady gait within a few days of starting to take temazepam 20mg at night. This was interpreted as temazepam toxicity. The symptoms disappeared when both drugs were stopped (See reference number 1).
After taking disulfiram 500mg daily for 14 to 16 days, plasma clearance of single doses of chlordiazepoxide and diazepam were reduced by 54 % and 41%, respectively, and half-lives were increased by 84 % and 37%, respectively. The plasma levels of chlordiazepoxide were approximately doubled. Oxazepam was also given following disulfiram treatment but changes in oxazepam pharmacokinetics were minimal. There was no difference in interaction between alcoholic subjects (without hepatic cirrhosis) and healthy subjects (See reference number 2).
Other studies show that pharmacokinetics of lorazepam and alprazolam are unaffected by disulfiram (See reference number 3,4)
Disulfiram inhibits initial metabolism (N-demethylation and oxidation) of both chlordiazepoxide and diazepam by liver so that an alternative but slower metabolic pathway is used. This results in accumulation of these benzodiazepines in body. In contrast, metabolism (glucuronidation) of oxazepam and lorazepam is minimally affected by disulfiram so that their clearance from body remains largely unaffected (See reference number 2,3). The possible interaction between disulfiram and temazepam is not understood, as temazepam is also mainly eliminated in urine as 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 clinically significant interaction between disulfiram and benzodiazepines, and this report is unconfirmed, as 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 dosage of benzodiazepine if necessary. Benzodiazepines that are metabolised by similar pathways to diazepam and chlordiazepoxide, may possibly interact in same way (e.g. bromazepam,clonazepam, clorazepate, prazepam, ketazolam, clobazam, flurazepam, nitrazepam, medazepam) but this needs confirmation. Alprazolam,oxazepam and lorazepam appear to be non-interacting alternatives.
Hardman M,Biniwale A, Clarke CE. Temazepam toxicity precipitated by disulfiram. Lancet (1994) 344, 1231–2.
MacLeod SM,Sellers EM, Giles HG, Billings BJ, Martin PR, Greenblatt DJ, Marshman JA.Interaction of disulfiram with benzodiazepines. Clin Pharmacol Ther (1978) 24, 583–9.
Sellers EM,Giles HG, Greenblatt DJ, Naranjo CA. Differential effects on benzodiazepine disposition by disulfiram and ethanol. Arzneimittelforschung (1980) 30, 882–6.
Diquet B,Gujadhur L, Lamiable D, Warot D, Hayoun H, Choisy H. Lack of interaction between disulfiram and alprazolam in alcoholic patients. Eur J Clin Pharmacol (1990) 38, 157–
60.