Drug Interaction Report

MONITOR: Based on in vitro inhibition data, coadministration with dalfopristin-quinupristin may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by dalfopristin-quinupristin.

MANAGEMENT: Caution is advised if dalfopristin-quinupristin must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever dalfopristin-quinupristin is added to or withdrawn from therapy.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.