etravirine
Regulatory sources consulted
Approved indications
- Treatment of HIV-1 in treatment-experienced patients, always with a boosted protease inhibitor and other antiretrovirals.
Contraindications
Absolute
- Hypersensitivity to etravirine.
- Concomitant elbasvir/grazoprevir.
Clinical warnings
- It may cause severe rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS; stop immediately for a severe reaction. — CIMA/AEMPS, ficha técnica 08468002
Drug interactions
- HighStrong CYP inducers such as rifampicin, carbamazepine, phenytoin, or St John’s wort
Mechanism: They reduce etravirine and may cause loss of virologic response.
Recommendation: The combination is not recommended.
CIMA/AEMPS, ficha técnica 08468002
- HighNarrow-therapeutic-index CYP3A4, CYP2C9, or CYP2C19 substrates
Mechanism: Etravirine induces CYP3A4 and inhibits CYP2C9/CYP2C19.
Recommendation: Review the substrate label and monitor efficacy or toxicity.
CIMA/AEMPS, ficha técnica 08468002
- HighDolutegravir
Mechanism: Etravirine markedly reduces dolutegravir exposure without a compatible boosted protease inhibitor.
Recommendation: Do not combine dolutegravir with etravirine unless the regimen includes atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir as labeled.
CIMA/AEMPS, ficha técnica 08468002
Adverse events
Common (≥1%)
Rash, diarrhea, nausea, headache, and peripheral neuropathy
Rare but serious
Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, and hepatitis
Pregnancy and lactation
It may be considered during pregnancy when clinically indicated. Do not breastfeed during HIV treatment.
Recent literature (PubMed)
Multiple factors may affect combined antiretroviral therapy (cART). We investigated the impact of food, beverages, dietary supplements, and alcohol on the pharmacokinetic and pharmacodynamic parameters of 33 antiretroviral drugs. Systematic review in adherence to PRISMA guidelines was performed, with 109 reports of 120 studies included. For each drug, meta-analyses or qualitative analyses were conducted. We have found clinically significant interactions with food for more than half of antiretroviral agents. The following drugs should be taken with or immediately after the meal: tenofovir disoproxil, etravirine, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosine, zalcitabine, zidovudine, efavirenz, amprenavir, fosamprenavir, and indinavir should be taken on an empty stomach for maximum patient benefit. Antiretroviral agents not mentioned above can be administered regardless of food. There is insufficient evidence available to make recommendations about consuming juice or alcohol with antiretroviral drugs. Resolving drug-food interactions may contribute to maximized cART effectiveness and safety. Múltiples factores pueden afectar la terapia antirretroviral combinada (cART). Investigamos el impacto de los alimentos, las bebidas, los suplementos dietéticos y el alcohol en los parámetros farmacocinéticos y farmacodinámicos de 33 medicamentos antirretrovirales. Se realizó la revisión sistemática en apego a las guías PRISMA, con 109 reportes de 120 estudios incluidos. Para cada fármaco se realizaron metanálisis o análisis cualitativos. Hemos encontrado interacciones clínicamente significativas con alimentos para más de la mitad de los fármacos antirretrovirales. Los siguientes medicamentos deben tomarse durante o inmediatamente después de comer: tenofovir, disoproxil, etravirina, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosina, zalc
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) have emerged as a vital cornerstone of highly active antiretroviral therapy (HAART) regimens, owing to their unique antiviral activity, low toxicity and high specificity. Diarylpyrimidines (DAPYs) as the second generation NNRTIs, represented by etravirine and rilpivirine, have attracted extensive attention due to their high anti-HIV potency. However, rapid emergence of resistant mutations, suboptimal pharmacokinetics (PK), and toxicity remain significant challenges. Recent structural modifications of DAPY analogues have focused on improving resistance profiles, optimizing PK properties (such as half-life and bioavailability), diversifying core structures through scaffold hopping, refining side-chain structures to enhance activity and selectivity, and reducing toxicity and side effects. Moreover, developing new DAPY analogues with broad-spectrum antiviral activity has become a key research priority. This review provides a comprehensive overview of the evolution of DAPYs from 2019 to 2023, including scaffold hopping and structural modifications of the right wing, left wing, central pyrimidine core, and linker, affording valuable insights for the future development of effective HIV-1 inhibitors.
This phase I study investigated potential drug-drug interactions of the maturation inhibitor GSK3640254 (GSK'254) with darunavir/ritonavir (DRV/RTV) and/or etravirine (ETR). In this randomized, open-label, single-sequence, multiple-dose study, healthy participants received GSK'254 200 mg once daily alone or coadministered with DRV/RTV 600/100 mg twice daily (BID; n = 19), ETR 200 mg BID (n = 19) or DRV/RTV 600/100 mg + ETR 200 mg BID (n = 16) under fed conditions. Primary endpoints were steady-state area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC0-τ ) and maximum observed concentration (Cmax ). Secondary endpoints included trough concentration (Cτ ), safety and tolerability. Pharmacokinetic parameters were calculated using standard noncompartmental analysis, and geometric least-squares mean ratios were derived from linear mixed-effects models. GSK'254 AUC0-τ (geometric least-squares mean ratio [90% confidence interval], 1.14 [1.00-1.29]), Cmax (1.07 [0.92-1.24]) and Cτ (1.17 [1.01-1.35]) were similar when administered alone and with DRV/RTV. Etravirine coadministration decreased GSK'254 AUC0-τ (0.53 [0.48-0.59]), Cmax (0.60 [0.53-0.68]) and Cτ (0.51 [0.39-0.66]). Similar reductions were not observed with GSK'254 + DRV/RTV + ETR (AUC0-τ , 0.94 [0.82-1.09]; Cmax , 0.89 [0.75-1.07]; Cτ , 1.02 [0.89-1.18]). GSK'254 had no meaningful effect on DRV/RTV or ETR concentrations. All reported adverse events (AEs) were grade 1; 3 led to withdrawal and resolved (rash, asymptomatic electrocardiogram T-wave inversion, periorbital oedema). Most common AEs were diarrhoea (n = 9) and headache (n = 7). No deaths or serious AEs occurred. GSK'254 pharmacokinetics was not meaningfully affected by DRV/RTV or DRV/RTV + ETR, but were reduced with only ETR; no new tolerability concerns were observed.