Disulfiram hepatotoxicity

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. 

Naltrexone can theoretically increase the risk of hepatotoxicity if combined with disulfiram, although in practice this... 

Prior to starting disulfiram, baseline liver function tests (LFTs) should be obtained, and patients should be monitored for hepatotoxicity. LFTs should be repeated at 2 weeks, 3 months, and 6 months, then twice yearly. The prescriber should wait at least 24 hours after the last drink before starting disulfiram, usually at a dose of 250 mg/day. 

Interactions between ethylene dichloride and other substances have been reported in animal studies. Specifically, a combination treatment with disulfiram caused testicular atrophy (not seen with either agent alone) and lowered the ethylene dichloride dose at which liver effects occurred. Increased hepatotoxic-ity has also been observed in some animals... 

Naltrexone is generally taken once a day in an oral dose of 50 mg for treatment of alcoholism. An extended-release formulation administered as an IM injection once every 4 weeks is also effective. The drug can cause dose-dependent hepatotoxicity and should be used with caution in patients with evidence of mild abnormalities in serum aminotransferase activity. The combination of naltrexone plus disulfiram should be avoided, since both drugs are potential hepatotoxins. Administration of naltrexone to patients who are physically dependent on opioids precipitates an acute withdrawal syndrome, so patients must be opioid-free before initiating naltrexone therapy. Naltrexone also blocks the therapeutic effects of usual doses of opioids. 

Several adverse effects of disulfiram itself (as opposed to the aldehyde that it allows to accumulate) have been described. They include neurological reactions and skin reactions, but hepatotoxicity is the only previously reported life-threatening reaction, and it is rare (3). 

A rare but potentially fatal idiosyncratic hepatotoxicity can occur with disulfiram. As a result, baseline liver function tests should be obtained and the patient monitored for hepatotoxicity by monitoring for symptoms and by repeating the liver function tests at 2 weeks,... 

A 54-year-old obese patient with type 2 diabetes and a history of alcoholism probably should not receive metformin because it can increase his risk of (A) A disulfiram-like reaction Excessive weight gain Hypoglycemia Lactic acidosis Serious hepatotoxicity... 

Disulfiram had no important effect on the metabolism of para-cetamoi in one study, but decreased the production of the glutathione (hepatotoxic) metaboiites in another. 

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