Drug interactions

Interactions with protease inhibitors complicate regimens containing etravirine. This is an especially important issue for a second-line NNRTI that may be used in salvage regimens with protease inhibitors.

Etravirine cannot be co-administered with boosted tipranavir/ritonavir (Aptivus), boosted fosamprenavir (Lexiva), full-dose ritonavir (Norvir 600 mg), boosted atazanavir (Reyataz), unboosted protease inhibitors, and other NNRTIs.

Etravirine blood levels increase by 17% when prescribed with lopinavir (Kaletra). This combination may be used, but should be administered with caution. Etravirine blood levels increase by 45% when given in combination with indinavir (Crixivan), which is why indinavir must be boosted with ritonavir when used in an etravirine-containing regimen.

Co-administration of etravirine with unboosted saquinavir (Invirase) can lower saquinavir levels by 40%. Co-administration of etravirine and unboosted indinavir (Crixivan) can lower indinavir levels by 50%.

Because etravirine is such a potent inducer of the cytochrome p450 CYP3A4 pathway, it greatly speeds up the metabolism of the CCR5 antagonist maraviroc (Celsentri, Selzentry). Co-administration can reduce total maraviroc concentrations over a 12-hour period by 53% (AUC₁₂) and peak levels of maraviroc (C_max) by 60%.

Therefore, if a patient isn't also taking a potent CYP3A4 inhibitor such as a protease inhibitor, the recommended clinical dose for maraviroc alongside etravirine is 600mg twice daily. However, if maraviroc is being dosed alongside etravirine and darunavir together, a dose reduction to 150mg twice daily is necessary. Data showed no effect of maraviroc on etravirine pharmacokinetics, so no dose adjustment of etravirine is necessary.

Etravirine cannot be given with carbamazepine, phenobarbital, phenytoin, rifabutin (if part of a protease inhibitor/ritonavir containing-regimen), rifampin, rifapentine, or St John's wort (Hypericum perforatum). It does not appear to affect blood levels of methadone. Etravirine may reduce levels of clopidogrel.

Etravirine should be used with caution alongside fluconazole or voriconazole, because these drugs have the potential to raise etravirine levels.

The efficacy of etravirine and/or its side-effect profile can change when given with inhibitors, inducers, or substrates of CYP3A4, CYP2C9, and CYP2C19. Further information on drug interactions is available at www.intelence-info.com.