Drug Interaction Report

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 with CYP450 3A4 and/or P-glycoprotein inducers. A dosage adjustment for maraviroc may be necessary if an interaction is suspected. Some authorities recommend a dosage of 300 mg twice daily when administered concomitantly with rifabutin and tipranavir/ritonavir or fosamprenavir/ritonavir. However, if a potent CYP450 3A4 inhibitor such as itraconazole, ketoconazole, delavirdine, clarithromycin, telithromycin, nefazodone, or any protease inhibitor (except tipranavir/ritonavir or fosamprenavir/ritonavir) is also used with the inducer, then maraviroc dosage should be reduced to 150 mg twice daily.

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.

Administration with food may reduce the bioavailability of maraviroc. According to the product labeling, coadministration of a 300 mg dose of maraviroc with a high-fat breakfast reduced maraviroc peak plasma concentration (Cmax) and systemic exposure (AUC) by 33% in healthy volunteers. However, no food restrictions were used in the clinical studies that demonstrated the safety and efficacy of maraviroc. Therefore, maraviroc can be taken with or without food at the recommended dosage.