efavirenz
Sources réglementaires consultées
Indications approuvées
- Traitement antiviral combiné du VIH-1 chez l’adulte, l’adolescent et l’enfant de 3 ans ou plus ayant un poids adapté à la présentation.
Contre-indications
Absolues
- Hypersensibilité à l’éfavirenz.
- Insuffisance hépatique sévère.
- Association à elbasvir/grazoprévir.
- Association au millepertuis.
Mises en garde cliniques
- Il peut provoquer symptômes neuropsychiatriques sévères, idées suicidaires, convulsions et encéphalopathie tardive ; évaluer antécédents et nouveaux symptômes. — CIMA/AEMPS, ficha técnica 79191
- Risque d’éruption sévère, d’hépatotoxicité et d’allongement du QT ; surveiller le foie et éviter les associations à risque. — CIMA/AEMPS, ficha técnica 79191
Interactions médicamenteuses
- SévèreVoriconazole
Mécanisme: L’éfavirenz réduit le voriconazole et le voriconazole augmente l’éfavirenz.
Recommandation: En cas d’association, utiliser voriconazole 400 mg toutes les 12 heures et éfavirenz 300 mg une fois par jour sous forme de gélules ; surveiller efficacité et toxicité.
CIMA/AEMPS, ficha técnica 79191
- SévèreInducteurs ou substrats CYP2B6/CYP3A4 et médicaments allongeant le QT
Mécanisme: L’éfavirenz présente de multiples interactions d’induction/inhibition et peut majorer le risque QT.
Recommandation: Évaluer chaque association et surveiller concentrations, réponse ou ECG selon le cas.
CIMA/AEMPS, ficha técnica 79191
- SévèreRifampicine
Mécanisme: Elle réduit l’exposition à l’éfavirenz.
Recommandation: Chez les personnes d’au moins 50 kg, augmenter l’éfavirenz à 800 mg une fois par jour pendant l’utilisation de rifampicine.
CIMA/AEMPS, ficha técnica 79191
Effets indésirables
Communs (≥1%)
Vertiges, insomnie, somnolence, troubles de la concentration, rêves anormaux et éruption
Rares mais graves
Syndrome de Stevens-Johnson, insuffisance hépatique, comportement suicidaire, convulsions et encéphalopathie
Grossesse et allaitement
Il ne doit pas être utilisé pendant la grossesse sauf si la situation clinique exige le traitement. Effectuer un test de grossesse avant l’instauration. Utiliser une contraception barrière en plus de la contraception hormonale pendant le traitement et 12 semaines après. Ne pas allaiter pendant le traitement du VIH.
Bibliographie récente (PubMed)
The provision of long-acting reversible contraceptive (LARC) methods is one of the best tools available to avoid high rates of unplanned pregnancy (UP), a public health problem that affects millions of women worldwide. In this review we provide an update regarding subdermal contraceptive implants including etonogestrel (ENG) and levonorgestrel (LNG) implants. Implants have been shown to be one of the most effective forms of contraceptive, with failure in only 4/1000 women for up to five years. Thus, their provision is an excellent strategy for reducing UPs. After a single intervention, implants provide long-term contraception with minimal side effects. Implants have few contraindications, but care must be taken to check for drug interactions with topiramate, rifampin and efavirenz. Although the ENG implant is approved for up to three years of use, research is ongoing into the possibility of extending its use beyond that period.
Dengue, caused by dengue virus (DENV), is now endemic in nearly 100 countries and infection incidence is reported in another 30 countries. Yearly an estimated 400 million cases and 2200 deaths are reported. Effective vaccines against DENV are limited and there has been significant focus on the development of effective antiviral against the disease. The World Health Organization has initiated research programs to prioritize the development and optimization of antiviral agents against several viruses including Flaviviridae. A significant effort has been taken by the researchers to develop effective antivirals against DENV. Several potential small-molecule inhibitors like efavirenz, tipranavir and dasabuvir have been tested against envelope and non-structural proteins of DENV, and are in clinical trials around the world. We recently developed one small molecule, namely 7D, targeting the host PF4-CXCR3 axis. 7D inhibited all 4 serotypes of DENV in vitro and specifically DENV2 infection in two different mice models. Although the development of dengue vaccines remains a high priority, antibody cross reactivity among the serotypes and resulting antibody-dependent enhancement (ADE) of infection are major concerns that have limited the development of effective vaccine against DENV. Therefore, there has been a significant emphasis on the development of antiviral drugs against dengue. This review article describes the rescue effects of some of the small molecule inhibitors to viral/host factors associated with DENV pathogenesis.
Although single-tablet, oral bictegravir, emtricitabine, and tenofovir alafenamide or dolutegravir and lamivudine are preferred regimens in several major guidelines and are widely used in many countries, they have not been compared in a fully powered trial. This study aimed to prospectively compare the 48-week results of dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide as maintenance therapies for people with HIV. PASO-DOBLE is a randomised, multicentre, open-label, non-inferiority trial done over 48 weeks at 30 sites in Spain. Adults (aged ≥18 years) with HIV-1, without previous viral failure, who had reached virological suppression on oral regimens containing at least one pill a day, cobicistat, efavirenz, or tenofovir disoproxil fumarate and no previous use of dolutegravir or bictegravir, and plasma HIV-1 RNA <50 copies per mL for at least 24 weeks were eligible. Participants were randomly assigned (1:1) to switch regimens to dolutegravir 50 mg and lamivudine 300 mg or bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily, using random block permutation, stratified by tenofovir alafenamide presence at baseline and sex assigned at birth. The primary endpoint was the proportion of participants with HIV RNA ≥50 copies per mL at week 48 in the intention-to-treat exposed population (ie, all participants who received at least one dose of study medication). The primary and safety analysis was done in the intention-to-treat exposed population. The non-inferiority margin was 4%. This trial is registered with ClinicalTrials.govNCT04884139 and is incomplete. Between July 14, 2021, and March 24, 2023, 553 participants initiated dolutegravir and lamivudine (n=277) or bictegravir, emtricitabine, and tenofovir alafenamide (n=276). The difference in the proportion of participants with HIV RNA ≥50 copies per mL between the dolutegravir and lamivudine group (six [2%] of 277) and bictegravir, emtricitabine, and t
Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors deem to have demonstrated clinical utility, meaning that testing improves treatment outcomes. The objective of this narrative review is to describe the current status of pharmacogenetic testing recommendations within clinical practice guidelines in the US. Guidelines were reviewed for pharmacogenetic testing recommendations for 21 gene-drug pairs that have well-established drug response associations and all of which are categorized as clinically actionable by the Clinical Pharmacogenetics Implementation Consortium. The degree of consistency within and between organizations in pharmacogenetic testing recommendations was assessed. Relatively few clinical practice guidelines that provide a pharmacogenetic testing recommendation were identified. Testing recommendations for HLA-B*57:01 before initiation of abacavir and G6PD before initiation of rasburicase, both of which are included in drug labeling, were mostly consistent across guidelines. Gene-drug pairs with at least one clinical practice guideline recommending testing or stating that testing could be considered included CYP2C19-clopidogrel, CYP2D6-codeine, CYP2D6-tramadol, CYP2B6-efavirenz, TPMT-thiopurines, and NUDT15-thiopurines. Testing recommendations for the same gene-drug pair were often inconsistent between organizations and sometimes inconsistent between different guidelines from the same organization. A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines, which could benefit patients and society by increasing clinical use of pharmacogenetic testing. Efavirenz is excreted into breastmilk and small amount