Drug interactions between Adrenocot and Selzentry

MONITOR: Coadministration with inducers of the CYP450 3A4 isoenzyme and/or P-glycoprotein efflux transporter may decrease the plasma concentrations of maraviroc, which is a substrate of both. According to the product labeling, administration of maraviroc (100 mg twice a day) with the potent CYP450 3A4/P-glycoprotein inducer rifampin (600 mg once a day) reduced the mean maraviroc peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 66%, 63% and 78%, respectively, compared to administration alone. When the same dosage of maraviroc was administered with efavirenz (600 mg once a day), maraviroc Cmax, AUC, and Cmin decreased by approximately 50% each. In contrast, maraviroc Cmax increased by 25% and AUC increased by 153% during coadministration with efavirenz (600 mg once a day) plus the potent CYP450 3A4 inhibitors lopinavir/ritonavir (400 mg/100 mg twice a day). An even greater increase of 2.3-fold in Cmax and 5-fold in AUC was observed during coadministration of maraviroc (300 mg twice a day) and efavirenz plus saquinavir/ritonavir (1000 mg/100 mg twice a day).

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution is advised if maraviroc is used in combination with CYP450 3A4 and/or P-glycoprotein inducers. A dosage adjustment for maraviroc may be necessary if an interaction is suspected. Maraviroc should be administered at a dosage of 600 mg twice daily during coadministration with potent CYP450 3A4 inducers such as efavirenz, rifampin, carbamazepine, phenobarbital, and phenytoin. However, if a potent CYP450 3A4 inhibitor such as itraconazole, ketoconazole, delavirdine, clarithromycin, telithromycin, nefazodone, or any protease inhibitor (except tipranavir plus ritonavir) is also used in combination with the inducer, then maraviroc dosage should be reduced to 150 mg twice daily.