Antiretroviral (non-nucleoside reverse transcriptase inhibitor)
Etravirine 100 mg; tabs.
HIV-1 infection, in combination with other antiretrovirals, intreatment-experienced adults with evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretrovirals.
Etravirine is an NNRTI. It works by blocking RNA-dependent and DNA-dependent DNA polymerase activity of HIV-1.
After oral administration, maximum plasma levels are reached in about 2.5-4 hours. For maximum absorption, etravirine should be taken after a meal. It is highly protein-bound, primarily to albumin and alpha 1-acid glycoprotein, and metabolized by the liver to mostly inactive metabolites. Mild-to-moderate hepatic impairment does not affect its metabolism, but patients with severe hepatic impairment have not been studied.
The approval for this drug was based on analyses of two randomized, double-blind, placebo-controlled studies that were conducted in clinically advanced, three-class antiretroviral treatment-experienced adults. These studies compared etravirine + background regimen with placebo + background regimen. All subjects received darunavir/ritonavir as part of their background regimen and at least two other investigator-selected antiretrovirals.
Subjects were treatment-experienced HIV-1 infected patients with plasma HIV-1 RNA levels of >5,000 copies/mL while on a stable antiretroviral regimen for at least eight weeks; they had at least one NNRTI resistance-associated mutation and three or more specific protease inhibitor (PI) mutations. Virologic response was defined as an undetectable viral load (<50 copies/mL of viral RNA) at 24 weeks. Pooled results for the two studies indicated that, at 24 weeks, 59.8% of the patients given etravirine + background regimen were responders, compared with 40.2% for the placebo group. At week 24, 74% of the etravirine-treated group had a viral load of <400 copies/mL, compared with 51.5% of the placebo group. Studies are continuing.
Take after meals. May disperse tabs in water and drink. 200 mg twice daily.
Severe hepatic impairment. Pregnancy (Cat. B). Nursing mothers: not recommended.
Concomitant tipranivir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, PIs without ritonavir (e.g., atazanavir, fosamprenavir, nelfinavir, indinavir), ritonavir (600 mg twice daily), NNRTIs (e.g., efavirenz, nevirapine, delavirdine): not recommended. Avoid rifampin, rifapentine, St. John’s wort, carbamazepine, phenytoin, phenobarbital; rifabutin with darunavir/ritonavir. May affect, or be affected by, drugs that induce or inhibit or are substrates of CYP3A4, CYP2C9, CYP2C19 (e.g., azole antifungals, immunosuppressants); monitor. Potentiated by lopinavir/ritonavir. May antagonize antiarrhythmics (e.g., amiodarone, bepridil, disopyramide, flecainide, lidocaine, mexiletine, propafenone, quinidine) (monitor), sildenafil. May potentiate warfarin, diazepam. May be antagonized by anticonvulsants, dexamethasone. Clarithromycin (consider azithromycin for treating MAC). Adjust statin dose (except pravastatin, rosuvastatin). Rifabutin (adjust dose with etravirine monotherapy).
Rash (may be serious, e.g., Stevens-Johnson syndrome, hypersensitivity, erythema multiforme; discontinue if occurs), GI upset, fat redistribution, immune reconstitution syndrome, lab value changes (e.g., lipids, blood glucose).
Report pregnant patients exposed to etravirine by calling 800.258.4263.
For more information, call877.732.2488 or visit www.Intelence-info.com