etravirine
Sources réglementaires consultées
Indications approuvées
- Traitement du VIH-1 chez les patients prétraités, toujours avec un inhibiteur de protéase potentialisé et d’autres antirétroviraux.
Contre-indications
Absolues
- Hypersensibilité à l’étravirine.
- Association à elbasvir/grazoprévir.
Mises en garde cliniques
- Elle peut provoquer éruption sévère, syndrome de Stevens-Johnson, nécrolyse épidermique toxique ou DRESS ; arrêter immédiatement en cas de réaction sévère. — CIMA/AEMPS, ficha técnica 08468002
Interactions médicamenteuses
- SévèreInducteurs puissants des CYP tels que rifampicine, carbamazépine, phénytoïne ou millepertuis
Mécanisme: Ils réduisent l’étravirine et peuvent entraîner une perte de réponse virologique.
Recommandation: L’association n’est pas recommandée.
CIMA/AEMPS, ficha técnica 08468002
- SévèreSubstrats CYP3A4, CYP2C9 ou CYP2C19 à marge thérapeutique étroite
Mécanisme: L’étravirine induit CYP3A4 et inhibe CYP2C9/CYP2C19.
Recommandation: Consulter le RCP du substrat et surveiller efficacité ou toxicité.
CIMA/AEMPS, ficha técnica 08468002
- SévèreDolutégravir
Mécanisme: L’étravirine réduit fortement l’exposition au dolutégravir en l’absence d’un inhibiteur de protéase potentialisé compatible.
Recommandation: Ne pas associer dolutégravir et étravirine sauf si le schéma comprend atazanavir/ritonavir, darunavir/ritonavir ou lopinavir/ritonavir selon le RCP.
CIMA/AEMPS, ficha técnica 08468002
Effets indésirables
Communs (≥1%)
Éruption, diarrhée, nausées, céphalées et neuropathie périphérique
Rares mais graves
Syndrome de Stevens-Johnson, nécrolyse épidermique toxique, DRESS et hépatite
Grossesse et allaitement
Elle peut être envisagée pendant la grossesse si cliniquement indiquée. Ne pas allaiter pendant le traitement du VIH.
Bibliographie récente (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.