Drug Interactions between Dolophine and metronidazole

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.

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GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of methadone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 8 study subjects stabilized on methadone maintenance treatment, ingestion of regular strength grapefruit juice (200 mL one-half hour before and 200 mL simultaneously with the daily methadone dose) for five days resulted in an approximately 17% mean increase in methadone peak plasma concentration (Cmax) and systemic exposure (AUC) and a 14% mean decrease in apparent clearance for both the R(+) and S(-) enantiomers. Grapefruit juice did not affect the time to peak level (Tmax), terminal half-life, or apparent volume of distribution of methadone. No signs or symptoms of methadone toxicity or changes in intensity of withdrawal symptoms were reported in the study.

MANAGEMENT: Given the interindividual variability in the pharmacokinetics of methadone, a more significant interaction with grapefruit juice in certain patients cannot be ruled out. Patients treated with methadone should preferably avoid or limit the consumption of grapefruit juice, particularly during the induction of maintenance treatment.

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GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

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