Drug Interaction Report

CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

ADJUST DOSING INTERVAL: Oral products containing zinc such as mineral supplements and multivitamins may interfere with the gastrointestinal absorption of cephalexin, ceftibuten or cephradine. In one pharmacokinetic study (n=12), concurrent administration of zinc sulfate (250 mg, single oral dose) and cephalexin (500 mg, single oral dose) decreased cephalexin maximum concentration (Cmax) and systemic exposure (AUC; 0-inf) by 31.05% and 27.4%, respectively. However, in the same study, when zinc sulfate was administered 3 hours after the cephalexin dose, no significant alteration in cephalexin pharmacokinetics were observed.

MANAGEMENT: Oral medications or mineral supplements that contain zinc are recommended to be administered at least 3 hours after the cephalexin, ceftibuten or cephradine dose.