Drug interactions between Agenerase and Selzentry

ADJUST DOSE: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of maraviroc, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of maraviroc (100 mg twice a day) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once a day) increased the mean maraviroc peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 3.5- and 5-fold, respectively, compared to administration alone. When the same dosage of maraviroc was administered with ritonavir (100 mg twice a day), maraviroc Cmax increased by nearly 1.3-fold and AUC by 2.6-fold. An even greater increase of nearly 5-fold in Cmax and 10-fold in AUC was observed during coadministration of maraviroc and saquinavir/ritonavir (1000 mg/100 mg twice a day). At 300 mg twice a day, mean maraviroc Cmax increased by approximately 2-fold and AUC by 3.6-fold during coadministration with atazanavir (400 mg once a day). When the same dosage of maraviroc was given with atazanavir/ritonavir (300 mg/100 mg once a day), maraviroc Cmax increased by 2.7-fold and AUC increased by nearly 5-fold. During coadministration with lopinavir/ritonavir (400 mg/100 mg twice a day), maraviroc Cmax and AUC increased by 2-fold and 4-fold, respectively. MANAGEMENT: Maraviroc should be administered at a dosage of 150 mg twice daily during coadministration with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, delavirdine, clarithromycin, telithromycin, nefazodone, and protease inhibitors (except tipranavir plus ritonavir). This dosage is recommended whether or not a concomitant CYP450 3A4 inducer (e.g., efavirenz, rifampin, carbamazepine, phenobarbital, phenytoin) is used.