atazanavir
Sources réglementaires consultées
Indications approuvées
- Traitement combiné de l’infection par le VIH-1 chez l’adulte et l’enfant à partir de 6 ans.
Contre-indications
Absolues
- Hypersensibilité ; hépatopathie sévère ; associations CYP3A expressément contre-indiquées, notamment rifampicine, millepertuis, simvastatine/lovastatine, pimozide, quétiapine, midazolam oral, triazolam et dérivés de l’ergot.
Mises en garde cliniques
- Il peut prolonger le PR et provoquer un bloc cardiaque ; surveiller en cas de troubles de conduction ou avec d’autres médicaments allongeant le PR. — CIMA/AEMPS, ficha técnica 84067
- Mise en garde majeure · Il peut provoquer hyperbilirubinémie, néphrolithiase, cholélithiase et maladie rénale chronique ; surveiller bilirubine et fonction rénale selon le risque. — CIMA/AEMPS, ficha técnica 84067
Interactions médicamenteuses
- SévèreInhibiteurs de la pompe a protons, antagonistes H2 et antiacides
Mécanisme: l’augmentation du pH gastrique réduit l’absorption de l’atazanavir.
Recommandation: Antiacides : administrer atazanavir 2 h avant ou 1 h après. Chez les patients naïfs, l’IPP ne doit pas depasser omeprazole 20 mg et se prend environ 12 h avant atazanavir 300 mg/ritonavir 100 mg ; les IPP ne sont pas recommandes chez les patients deja traités. Avec un antagoniste H2 chez les patients deja traités, ne pas depasser famotidine 20 mg deux fois par jour et administrer atazanavir/ritonavir simultanément ou au moins 10 h après ; sans ritonavir, administrer atazanavir 400 mg au moins 2 h avant et 10 h après, avec famotidine limitee a 20 mg par prise et 40 mg/jour.
FDA label, set_id 165cff62-b284-4a27-a65d-9ec8a5bfcdd8
- SévèreTénofovir disoproxil et modulateurs du CYP3A
Mécanisme: Ils peuvent modifier l’exposition à l’atazanavir ou au médicament associé.
Recommandation: Utiliser le schéma potentialisé et les ajustements spécifiques ; revoir toutes les associations.
CIMA/AEMPS, ficha técnica 84067
Effets indésirables
Communs (≥1%)
Hyperbilirubinémie, nausées, diarrhée, céphalées et éruption
Rares mais graves
Bloc cardiaque, hépatotoxicité, néphrolithiase, cholélithiase et réactions cutanées sévères
Grossesse et allaitement
Il peut être utilisé pendant la grossesse lorsqu’il est cliniquement indiqué avec un schéma adapté. Surveiller pendant les premiers jours tout nouveau-né exposé in utero en raison du risque d’hyperbilirubinémie sévère. Ne pas allaiter en cas de VIH sous traitement.
Bibliographie récente (PubMed)
Viruses cause a variety of diseases in the human body. Antiviral agents are used to prevent the production of disease-causing viruses. These agents obstruct and kill the virus's translation and replication. Because viruses share the metabolic processes of the majority of host cells, finding targeted medicines for the virus is difficult. In the ongoing search for better antiviral agents, the USFDA approved EVOTAZ, a new drug discovered for the treatment of Human Immunodeficiency Virus (HIV). It is a once-daily (OD) fixed-dose combination of Cobicistat, a cytochrome P450 (CYP) enzyme inhibitor, and Atazanavir, a protease inhibitor. The combination drug was created in such a way that it can inhibit both CYP enzymes and proteases at the same time, resulting in the virus's death. The drug is not effective in children under the age of 18; however, it is still being studied for various parameters. This review article focuses on EVOTAZ's preclinical and clinical aspects, as well as its efficacy and safety profiles.
Children living with human immunodeficiency virus (HIV) have limited options for second-line antiretroviral therapy (ART). In this open-label trial with a 2-by-4 factorial design, we randomly assigned children with HIV who had first-line treatment failure to receive second-line therapy with tenofovir alafenamide fumarate (TAF)-emtricitabine or standard care (abacavir or zidovudine, plus lamivudine) as the backbone and dolutegravir or ritonavir-boosted darunavir, atazanavir, or lopinavir as the anchor drug. The primary outcome was a viral load of less than 400 copies per milliliter at 96 weeks. We hypothesized that TAF-emtricitabine would be noninferior to standard care, that dolutegravir and ritonavir-boosted darunavir would each be superior to ritonavir-boosted lopinavir and atazanavir analyzed in combination, and that ritonavir-boosted atazanavir would be noninferior to ritonavir-boosted lopinavir. Safety was also assessed. A total of 919 children underwent randomization; 458 were assigned to receive TAF-emtricitabine, and 461 to receive standard care. Assigned anchor drugs were dolutegravir (229 participants), ritonavir-boosted darunavir (232), ritonavir-boosted atazanavir (231), and ritonavir-boosted lopinavir (227). The median age of participants was 10 years, and 497 (54.1%) were male. The median viral load at baseline was 17,573 copies per milliliter. At week 96, TAF-emtricitabine was superior to standard care: the adjusted difference in the percentage of participants with a viral load of less than 400 copies per milliliter was 6.3 percentage points (95% confidence interval [CI], 2.0 to 10.6; P = 0.004). Dolutegravir was superior to ritonavir-boosted lopinavir and atazanavir analyzed in combination (adjusted difference, 9.7 percentage points; 95% CI, 4.8 to 14.5; P<0.001), but ritonavir-boosted darunavir was not (adjusted difference, 5.6 percentage points; 95% CI, 0.3 to 11.0; P = 0.04 [prespecified threshold, P = 0.03]). Ritonavir-boosted atazanavir was noni