Disulfiram dosage

Disulfiram produces a variety of adverse effects, which commonly include drowsiness, lethargy, and fatigue (Chick 1999). Other more serious adverse effects, such as optic neuritis, peripheral neuropathy, and hepatotoxicity, are rare. Psychiatric effects of disulfiram are also uncommon. They probably occur only at higher dosages of the drug and may result from the inhibition by disulfiram of a variety of enzymes in addition to ALDH. Included among the enzymes inhibited by disulfiram is dopamine P-hydroxylase, inhibition of which increases dopamine levels, which in turn can exacerbate psychotic symptoms in patients with schizophrenia and occasionally may result in psychotic or depressive symptoms in patients without schizophrenia. 

Disulfiram is usually given orally. Because there is an increased risk of side effects and toxic hazards as the dosage is increased, the daily dosage prescribed in the United States has been limited to 250—500 mg/day. However, efforts to titrate the dosage of disulfiram in relation to a challenge dose of ethanol indicated that some patients require in excess of 1 g/day of disulfiram to reach blood levels sufficient to produce a DER (Brewer 1984). 

Only a few well-documented drug combinations with phenytoin may necessitate dosage adjustment. Coadministration of the following drugs can result in elevations of plasma phenytoin levels in most patients cimetidine, chloramphenicol, disulfiram, sulthiame, and isoniazid (in slow acetylators). Phenytoin often causes a decline in plasma carbamazepine levels if these two drugs are given concomitantly. 

Disulfiram Potentiation (162,163) Inhibition of microsomal enzymes (162) Adjust dosage... 

Retrobulbar neuritis can be part of a disulfiram-induced polyneuritis, with dramatic reduction in visual acuity and impaired colour perception (SEDA-10, 349) (12). This complication is rare but serious. It occurs at dosages of 500 mg/day, and there is a latent period of 2-36 months. Tobacco abuse is thought to be a predisposing factor. Disulfiram can cause optic neuropathy (13,14). 

Certain drugs inhibit non-microsomal metabolic pathways. Metronidazole, like disulfiram, inhibits aldehyde dehydrogenase, the enzyme that normally oxidizes acetaldehyde to acetic acid in the metabolic pathway for ethanol. Allopurinol inhibits xanthine oxidase, the enzyme that catalyses the oxidation of hypoxanthine to xanthine and xanthine to uric acid. Because azathioprine and 6-mercaptopurine are metabolized by xanthine oxidase, the dosage of these drugs (synthetic xanthine analogues), when used concomitantly with... 

The interaction between phenytoin and disulfiram is established, moderately well documented, clinieally important and potentially serious. It seems to occur in most patients and develops rapidly. Reeovery may take 2 to 3 weeks after the disulfiram is withdrawn. It has been suggested that the dosage of phenytoin could be reduced to accommodate the interaetion, but it may be difficult to maintain the balance required. Monitor very closely if both drugs are given. ... 

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. 

Information appears to be limited to this study but it would seem to be a clinically important interaction. Monitor the serum levels of theophylline and its effects if disulfiram is added, anticipating the need to reduce the theophylline dosage. Note that the extent of this interaction appears to depend upon the dosage of disulfiram used. 

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