Drug Interactions between oritavancin and Synalgos-DC

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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever oritavancin is added to or withdrawn from therapy.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

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.