Drug Interactions between maraviroc and Tuinal

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.

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.