Temazepam Disulfiram

Disulfiram inhibits CYP enzymes 1A2, 2C9, and 3A4 many benzodiazepines are metabolized via these pathways lorazepam, temazepam, and oxazepam are NOT metabolized via the CYP4S0 system and are reasonable alternatives. 

Temazepam (Restoril) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia, anxiety, depression, panic attacks Action Benzodiaz ine Dose 15-30 mg PO hs PRN X in elderly Caution [X, /-] Potentiates CNS dqjressive effects of opioids, barbs, EtOH, antihistamines, MAOIs, TCAs Contra NAG Disp Caps SE Confusion, dizziness, drowsiness, hangover Interactions T Effects W/ cimetidine, disulfiram, kava kava, valerian T CNS depression W/ anticonvulsants, CNS depressants, EtOH t effects OF haloperidol, phenytoin X effects W/ aminophylline, dyphylline, OCPs, oxtriphylline, rifampin, theophylline, tobacco X effects OF levodopa EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH can T CNS depression abruptly D/C after >10 d use may cause withdrawal OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote, activated charcoal may be effective... 

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. 

A man taking disulfiram 200 mg daily developed confusion, drowsiness, slurred speech and an unsteady gait within a few days of starting to take temazepam 20 mg at night. This was interpreted as temazepam toxicity. The symptoms disappeared when both drugs were stopped. ... 

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. 

Hardman M, Biniwale A, Clarke CE. Temazepam toxicity precipitated by disulfiram. Lancet (1994) 344, 1231-2. 

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