Dolutegravir Dosage for Patients Taking Etravirine
Coadministering etravirine and dolutegravir results in substantially decreased levels of dolutegravir. However, adding lopinavir/ritonavir or boosted darunavir to this combination can restore appropriate dolutegravir pharmacokinetics.
The combination of dolutegravir (a promising once-daily unboosted integrase inhibitor) and etravirine (a second-generation nonnucleoside reverse transcriptase inhibitor) is a potentially attractive option for patients infected with multidrug-resistant HIV. However, possible interactions between the two drugs, which share similar metabolic pathways, are still being evaluated.
Two open-label crossover studies were recently conducted among HIV-uninfected men (33 total) to evaluate the pharmacokinetics (PK) of dolutegravir in three scenarios: when it is administered alone, when it is administered only with etravirine, and when it is administered with etravirine plus either ritonavir-boosted darunavir or lopinavir/ritonavir. Both studies were conducted by the makers of dolutegravir.
Etravirine alone decreased exposure to dolutegravir by 70% to 90%. However, this effect was markedly attenuated when either of the boosted protease inhibitors was added, leading the investigators to conclude that no dose modification is required when all three drugs are administered together.
Abstract and Introduction
Abstract
Coadministering etravirine and dolutegravir results in substantially decreased levels of dolutegravir. However, adding lopinavir/ritonavir or boosted darunavir to this combination can restore appropriate dolutegravir pharmacokinetics.
Introduction
The combination of dolutegravir (a promising once-daily unboosted integrase inhibitor) and etravirine (a second-generation nonnucleoside reverse transcriptase inhibitor) is a potentially attractive option for patients infected with multidrug-resistant HIV. However, possible interactions between the two drugs, which share similar metabolic pathways, are still being evaluated.
Two open-label crossover studies were recently conducted among HIV-uninfected men (33 total) to evaluate the pharmacokinetics (PK) of dolutegravir in three scenarios: when it is administered alone, when it is administered only with etravirine, and when it is administered with etravirine plus either ritonavir-boosted darunavir or lopinavir/ritonavir. Both studies were conducted by the makers of dolutegravir.
Etravirine alone decreased exposure to dolutegravir by 70% to 90%. However, this effect was markedly attenuated when either of the boosted protease inhibitors was added, leading the investigators to conclude that no dose modification is required when all three drugs are administered together.
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