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monitoring for the development of adverse effects may be appropriate for some drugs whenever oritavancin is added to or withdrawn from therapy.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 reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.