atazanavir
Regulatory sources consulted
Approved indications
- Combination treatment of HIV-1 infection in adults and pediatric patients aged 6 years and older.
Contraindications
Absolute
- Hypersensitivity; severe liver disease; expressly contraindicated CYP3A combinations, including rifampin, St John’s wort, simvastatin/lovastatin, pimozide, quetiapine, oral midazolam, triazolam, and ergots.
Clinical warnings
- It may prolong PR and cause heart block; monitor in conduction disorders or with other PR-prolonging drugs. — CIMA/AEMPS, ficha técnica 84067
- Major warning · It may cause hyperbilirubinemia, nephrolithiasis, cholelithiasis, and chronic kidney disease; monitor bilirubin and renal function according to risk. — CIMA/AEMPS, ficha técnica 84067
Drug interactions
- HighProton-pump inhibitors, H2 antagonists, and antacids
Mechanism: Increased gastric pH reduces atazanavir absorption.
Recommendation: Antacids: give atazanavir 2 h before or 1 h after. In treatment-naive patients, the PPI must not exceed omeprazole 20 mg and is taken about 12 h before atazanavir 300 mg/ritonavir 100 mg; PPIs are not recommended in treatment-experienced patients. With an H2 antagonist in treatment-experienced patients, do not exceed famotidine 20 mg twice daily and give atazanavir/ritonavir simultaneously or at least 10 h afterward; without ritonavir, give atazanavir 400 mg at least 2 h before and 10 h after, with famotidine limited to 20 mg per dose and 40 mg/day.
FDA label, set_id 165cff62-b284-4a27-a65d-9ec8a5bfcdd8
- HighTenofovir disoproxil and CYP3A modulators
Mechanism: They may change atazanavir or concomitant-drug exposure.
Recommendation: Use the boosted regimen and specific adjustments; review all combinations.
CIMA/AEMPS, ficha técnica 84067
Adverse events
Common (≥1%)
Hyperbilirubinemia, nausea, diarrhea, headache, and rash
Rare but serious
Heart block, hepatotoxicity, nephrolithiasis, cholelithiasis, and severe skin reactions
Pregnancy and lactation
It may be used during pregnancy when clinically indicated with an appropriate regimen. Monitor every infant exposed in utero during the first days of life for severe hyperbilirubinemia. Do not breastfeed if you have HIV and receive treatment.
Recent literature (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