Maraviroc dose should be increased to 600 mg twice daily when co-administered with efavirenz in the ABSENCE of a PI or other potent CYP3A4 inhibitor. Coadministration of efavirenz (600 mg once daily) and maraviroc (100 mg twice daily) decreased maraviroc AUC (45%) and Cmax (51%). Efavirenz concentrations were not measured, but no effect is expected. 

The CYP3A inducer efavirenz decreased the Cmax and AUC of maraviroc. Coadministration of efavirenz (600 mg once daily) and maraviroc (100 mg twice daily) decreased maraviroc AUC, Cmax and Cmin by 45%, 51% and 45%, respectively (n=12). When compared to maraviroc 100 mg twice daily alone, coadministration of efavirenz (600 mg once daily) and maraviroc (200 mg twice daily) to 12 subjects increased maraviroc AUC, Cmax and Cmin by 15%, 16% and 9%, respectively. The recommended dose of maraviroc when coadministered with efavirenz (without a potent CYP3A inducer) is 600 mg twice daily. No additional maraviroc dose adjustment when coadministered with potent CYP3A inducers is required in patients with CrCl 30-80 mL/min. Maraviroc is contraindicated in patients with severe renal impairment (<30 mL/min) or ESRD on regular hemodialysis who are receiving potent CYP3A inducers.

Coadministration of maraviroc (100 mg twice daily) and efavirenz (600 mg once daily) decreased maraviroc AUC and Cmax by 45% and 51%, respectively. Efavirenz concentrations were not measured, but no effect is expected. Refer to the SmPC for maraviroc.

Coadministration of maraviroc (100 mg twice daily) and efavirenz (600 mg once daily) was studied in 12 subjects. The Cmax, AUC and Cmin of maraviroc decreased by 51%, 45% and 45%, respectively. Refer to the full prescribing information for maraviroc for guidance on coadministration with efavirenz.

Coadministration of maraviroc (100 mg twice daily) and efavirenz (600 mg once daily) was studied in 12 HIV- subjects. In the presence of efavirenz, maraviroc AUC and Cmax decreased by 51% and 66%, respectively. Dose adjustment of maraviroc to 200 mg twice daily adequately compensated for the interactions (GMR for AUC and Cmax of 1.1 and 1.2, respectively). Measurement of 6ß-OH cortisol/cortisol ratio indicated that CYP3A4 was moderately induced by efavirenz (2.4-fold). 

Coadministration of maraviroc (300 mg single dose) to HIV+ subjects stable on an efavirenz containing regimen (600 mg once daily with 3TC/ZDV or ddI/TDF) reduced maraviroc AUC by ~50% when compared to historical data. Cmax was reduced by 67% (EFV/3TC/ZDV, n=8) or 76% (EFV/ddI/TDF, n=8). 

Efavirenz + Boosted PIs 
LHPG Comment: Note the difference in recommendations for fosamprenavir/ritonavir/efavirenz. The European SPC does not recommend coadministration, but the US Prescribing Information indicates 150 mg twice daily.

Maraviroc dose should be decreased to 150 mg twice daily when co-administered with efavirenz in the PRESENCE of a PI other than tipranavir/ritonavir where the dose should be 600 mg twice daily. 
Coadministration of efavirenz (600 mg once daily), lopinavir/ritonavir (400/100 mg twice daily) and maraviroc (300 mg twice daily) increased maraviroc AUC by 2.53-fold and Cmax by 1.25-fold. Efavirenz and lopinavir/ritonavir concentrations were not measured, but no effect expected. 
Coadministration of efavirenz (600 mg once daily), saquinavir/ritonavir (1000/100 mg twice daily) and maraviroc (100 mg twice daily) increased maraviroc AUC by 5.00-fold and Cmax by 2.26-fold. Efavirenz and saquinavir/ritonavir concentrations not measured, but no effect expected. 
Efavirenz and atazanavir/ritonavir  or darunavir/ritonavir has not been studied. Based on the extent of inhibition by atazanavir/ritonavir or darunavir/ritonavir in the absence of efavirenz, an increased exposure is expected.

Coadministration of lopinavir/ritonavir (400/100 mg twice daily), efavirenz (600 mg once daily) and maraviroc (300 mg twice daily) increased maraviroc AUC, Cmax and Cmin by 2.53-fold, 1.25-fold and 6.29-fold, respectively (n=11). 
Coadministration of saquinavir/ritonavir (1000/100 mg twice daily), efavirenz (600 mg once daily) and maraviroc (100 mg twice daily) increased maraviroc AUC, Cmax and Cmin by 5-fold, 2.26-fold and 8.42-fold, respectively (n=11). When maraviroc is given with efavirenz and PIs (except tipranavir/ritonavir, the recommended dose of maraviroc is 150 mg twice daily.