Drug Interaction Report

MONITOR: Coadministration with oritavancin may decrease the plasma concentrations and therapeutic effects drugs that are substrates of CYP450 3A4 and/or 2D6. The proposed mechanism is increased clearance due to oritavancin-mediated induction of these isoenzymes. In a screening drug interaction study in 16 healthy volunteers, a single 1,200 mg dose of oritavancin decreased midazolam systemic exposure (AUC) by 18% and the urinary dextromethorphan-to-dextrorphan ratio by 31%, indicating weak induction of CYP450 3A4 and 2D6, respectively.

MANAGEMENT: Caution is advised when oritavancin used concomitantly with drugs that are substrates of CYP450 3A4 and/or 2D6, particularly sensitive substrates or those for which minimal concentration changes may lead to therapeutic failure. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever oritavancin is added to or withdrawn from therapy. Individual product labeling for the CYP450 3A4 and/or 2D6 substrate(s) should be consulted for further guidance.

GENERALLY AVOID: 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 and instructed to avoid alcoholic beverages and products containing alcohol or propylene glycol while using oral, intravenous, or vaginal preparations of a nitroimidazole. Alcoholic beverages should not be consumed for up to 3 days after completion of systemic nitroimidazole therapy.