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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever oritavancin is added to or withdrawn from therapy.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.

ADJUST DOSE: Smoking tobacco may decrease the steady-state systemic exposure of istradefylline by 38% to 54%.

MANAGEMENT: The possibility of reduced therapeutic effects of istradefylline should be considered in smokers. The manufacturer recommends an istradefylline dosage of 40 mg once daily in patients who smoke 20 or more cigarettes (or the equivalent amount of another tobacco product) per day.