Coadministration of efavirenz and raltegravir (400 mg single dose) decreased raltegravir AUC by 36%, Cmax by 36% and Cmin by 21%. Coadministration of efavirenz and raltegravir (1,200 mg single dose) decreased raltegravir AUC, C24 and Cmax by 14%, 6% and 9%, respectively. No dose adjustment required for raltegravir (400 mg twice daily and 1,200 mg once daily).

Efavirenz did not have a clinically meaningful effect on the pharmacokinetics of 400 mg twice daily raltegravir or 1200 mg once daily raltegravir. No dose adjustment is required when raltegravir 400 mg twice daily or 1200 mg once daily is coadministered. Coadministration of efavirenz (600 mg once daily) and raltegravir (400 mg single dose) decreased raltegravir Cmax, AUC and Cmin by 36%, 36% and 21% (n=9). Coadministration of efavirenz (600 mg once daily) and raltegravir (1200 mg single dose) decreased raltegravir Cmax, AUC and Cmin by 9%, 14% and 6% (n=21).

Coadministration of raltegravir (100 mg single dose) and efavirenz decreased raltegravir AUC, Cmax and C12 by 36%, 36% and 21%, respectively, via UGT1A1 induction. No dosage adjustment is necessary for raltegravir.

Based on the results of drug interaction studies, no dosage adjustment is recommended when efavirenz is given with raltegravir. Coadministration of raltegravir (400 mg single dose) and efavirenz (600 mg once daily) was studied in 9 subjects. Raltegravir Cmax, AUC and Cmin decreased by 36%, 36% and 21%, respectively.

The potential effect of efavirenz on raltegravir pharmacokinetics was examined in healthy subjects administered raltegravir alone (400 mg single dose), followed by efavirenz (600 mg once daily) for 14 days with a single dose of raltegravir (400 mg) on day 12. In the presence of efavirenz, raltegravir pharmacokinetics were moderately to weakly reduced: GMR (90% CI) for C12h, AUC and Cmax were 0.79 (0.49, 1.28), 0.64 (0.52, 0.80) and 0.64 (0.41, 0.98), respectively. Though plasma concentrations of raltegravir were reduced by efavirenz, the degree of this reduction was not considered to be clinically meaningful and no dose adjustment is required.