Drug Interaction Report

MONITOR: Coadministration with oritavancin may increase the plasma concentrations of drugs that are substrates of CYP450 2C9, and/or 2C19. The mechanism is decreased clearance due to inhibition of these isoenzymes by oritavancin. In a screening drug interaction study in 16 healthy volunteers, a single 1,200 mg dose of oritavancin increased the omeprazole-to-5-hydroxyomeprazole plasma ratio by 15% and the systemic exposure (AUC) of warfarin by 31%, indicating weak inhibition of CYP450 2C19 and CYP450 2C9, respectively.

MANAGEMENT: Caution is advised when oritavancin used concomitantly with drugs that are substrates of CYP450 2C9 and/or 2C19, particularly sensitive substrates, or those with a narrow therapeutic range. Dosage adjustments as well as closer clinical and laboratory monitoring for the development of adverse effects may be appropriate for some drugs whenever oritavancin is added to or withdrawn from therapy. Individual product labeling should be consulted for further guidance.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of zafirlukast. In two separate studies, one using a high-fat and the other a high-protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%.

MANAGEMENT: To ensure maximal oral absorption, zafirlukast should be administered at least 1 hour before or 2 hours after meals.