Population PK analysis showed that the effect of emtricitabine/tenofovir disaproxil fumarate on the pharmacokinetics of raltegravir (1,200 mg once daily) was minimal (12% increase in relative bioavailability), and was not statistically or clinically significant. Co-administration of emtricitabine/tenofovir disaproxil fumarate and raltegravir 1,200 mg once daily is permitted. No dose adjustment required for raltegravir (400 mg twice daily and 1,200 mg once daily) or tenofovir disoproxil fumarate.

Coadministration of raltegravir (400 mg twice daily for 4 days) and tenofovir-DF (300 mg once daily for 7 days) alone and in combination for 4 days was studied in HIV- subjects. Pharmacokinetic profiles were also determined in HIV+ patients given raltegravir monotherapy alone or in combination with tenofovir-DF/lamivudine. In healthy volunteers raltegravir AUC and Cmax were modestly increased in the presence of tenofovir-DF (49% and 64%, respectively), while there was no effect of tenofovir-DF on raltegravir Cmin (3% increase). However, there was a modest increase of 42% in Cmin in HIV-infected patients. Raltegravir only had a small effect on tenofovir-DF AUC (10% decrease), Cmax (23% decrease) and Cmin (13% decrease). The authors conclude that coadministration of raltegravir and tenofovir-DF does not change the pharmacokinetics of either drug to a clinically meaningful degree and consequently may be coadministered without dose adjustments.