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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever oritavancin is added to or withdrawn from therapy.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: Alcohol may potentiate the cardiovascular effects of amphetamines. The exact mechanism of interaction is unknown. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state. The interaction was suspected in a case report of a 20-year-old male who experienced retrosternal chest pain shortly after drinking alcohol and taking a double dose of his amphetamine/dextroamphetamine medication (Adderall 15 mg X 2) to stay alert. The patient had no family history of cardiovascular diseases, and his past medical history was remarkable only for ADHD. Prior to the episode, the patient had not taken his medication for weeks and had been drinking whiskey the previous three nights before going to bed. The patient was diagnosed with myocardial infarction likely secondary to amphetamine-induced coronary vasospasm.

MANAGEMENT: Concomitant use of amphetamines and alcohol should be avoided if possible, especially in patients with a history of heart disease.