Drug Interaction Report

CONTRAINDICATED: Consumption of ethanol during treatment with disulfiram may cause flushing, nausea, blurred vision, dyspnea, tachypnea, tachycardia, and hypotension. Death has been reported. The mechanism is probably related to inhibition of aldehyde dehydrogenase, the enzyme responsible for the oxidation of acetaldehyde to acetyl CoA. Accumulation of acetaldehyde probably results.

MANAGEMENT: Ethanol should be avoided in patients receiving disulfiram.

MONITOR: Oral caffeine may significantly increase the bioavailability of melatonin. The proposed mechanism is inhibition of CYP450 1A2 first-pass metabolism. After administration of melatonin 6 mg and caffeine 200 mg orally (approximately equivalent to 1 large cup of coffee) to 12 healthy subjects, the mean peak plasma concentration (Cmax) of melatonin increased by 137% and the area under the concentration-time curve (AUC) increased by 120%. The metabolic inhibition was greater in nonsmokers (n=6) than in smokers (n=6). The greatest effect was seen in subjects with the *1F/*1F genotype (n=7), whose melatonin Cmax increased by 202%. The half-life did not change significantly. The clinical significance of this interaction is unknown.

According to some authorities, alcohol may reduce the effect of melatonin on sleep. The mechanism of this interaction is not fully understood.

In addition, CYP450 1A2 inducers like cigarette smoking may reduce exogenous melatonin plasma levels. In a small clinical trial (n=8), habitual smokers had their melatonin plasma levels measured two times, each after a single oral dose of 25 mg of melatonin. They had smoked prior to the first measurement but had not smoked for 7 days prior to the second. Cigarette smoking significantly reduced melatonin plasma exposure (AUC) as compared to melatonin levels after 7 days of smoking abstinence (7.34 +/- 1.85 versus 21.07 +/- 7.28 nmol/L*h, respectively).

MANAGEMENT: Caution and monitoring are recommended if melatonin is used with inhibitors of CYP450 1A2 like caffeine or inducers of CYP450 1A2 like cigarette smoking. Consumption of alcohol should be avoided when taking melatonin.