Antiretroviral protease inhibitor (PI)
Atazanavir is an antiretroviral medicine used to treat HIV infection, always in combination with other medicines. It is generally well tolerated, but can cause jaundice (yellow skin and eyes) due to raised bilirubin, which is not harmful but should be monitored.
Also known as: Reyataz
Combining Atazanavir with Omeprazole substantially reduces Atazanavir concentrations, with a risk of virological failure.
Atazanavir absorption depends on an acidic gastric pH: omeprazole, by suppressing acid secretion, reduces the solubility and plasma concentration of atazanavir in a clinically significant way, with a risk of loss of virologic response and development of resistance (the atazanavir label explicitly warns about this risk). If the combination is unavoidable, the label recommends not exceeding a PPI dose comparable to omeprazole 20 mg and taking it approximately 12 hours before atazanavir 300 mg with ritonavir 100 mg, with virological monitoring. In HIV patients, any drug that raises gastric pH must be managed carefully and reassessed.
Omeprazole + atazanavir: the PPI markedly reduces atazanavir exposure, with a risk of antiretroviral failure. Avoid; if needed, PPI ≤20 mg 12 hours before with boosting and monitoring.
Proton pump inhibitors such as Omeprazole raise gastric pH, reducing Atazanavir absorption and lowering its exposure.
Monitor viral load and, if available, CD4; reassess when Omeprazole is started or stopped.
Detectable viral load or signs of therapeutic failure after starting Omeprazole require reassessment of the antiretroviral regimen.
Avoid the combination when possible; if unavoidable, prefer H2-receptor antagonists and/or separate dosing times; do not use a PPI with low doses of Atazanavir.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8 ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Atazanavir with Antacids reduces Atazanavir absorption, with a risk of reduced efficacy.
Atazanavir is an HIV protease inhibitor whose absorption depends on an acidic gastric pH: antacids, by neutralising the acid, reduce the drug solubility and plasma concentration, with a risk of loss of antiretroviral efficacy and viral resistance. The atazanavir label recommends administering the drug 2 hours before or 1 hour after antacids (and buffered medications). In patients on antiretroviral therapy, any drug that raises gastric pH (antacids, H2 antagonists, proton pump inhibitors) must be managed with caution and with the recommended spacing.
Antacids + atazanavir: raised gastric pH reduces atazanavir solubility and absorption. Administer atazanavir 2 hours before or 1 hour after antacids.
Antacids (aluminium/magnesium hydroxide) raise gastric pH and may chelate Atazanavir, lowering its bioavailability.
Monitor the virological response to the antiretroviral regimen.
Detectable viral load with regular antacid use requires reassessment of the regimen.
Separate administration: take antacids at least 2 hours before or after Atazanavir.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8 ; approved Antacids label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c72f0736-ee20-45b4-baf0-b80f1e3fa9cb — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Atazanavir with Warfarin may potentiate the anticoagulant effect and increase the risk of serious bleeding.
Atazanavir inhibits CYP3A4 (and UGT1A1), enzymes involved in the metabolism of both warfarin enantiomers. The inhibition can increase warfarin exposure and raise the INR, with increased bleeding risk. Since atazanavir is used with ritonavir or cobicistat (also inhibitors), the effect can be even more pronounced. The INR should be monitored frequently at initiation, during and after antiretroviral discontinuation, and the warfarin dose adjusted accordingly.
Atazanavir inhibits CYP3A4 and UGT1A1 and can raise warfarin levels and the INR. Monitor the INR when starting, adjusting and stopping atazanavir.
Atazanavir inhibits metabolic pathways of Warfarin; the label warns of the potential for serious and/or potentially fatal bleeding with co-administration.
Watch for bleeding signs; regular INR testing at start and dose changes.
A high INR with active bleeding requires immediate discontinuation of the anticoagulant and urgent evaluation.
Monitor the INR frequently and adjust the Warfarin dose during co-administration.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Alcohol adds hepatotoxicity to that of atazanavir, with increased risk in patients with hepatitis B or C.
Avoid alcohol during treatment.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8
Taking atazanavir with food improves its absorption and reduces plasma level variability.
Take with food, preferably at the same daily meal.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8
Atazanavir prolongs the PR interval and can cause asymptomatic atrioventricular block; the risk increases with pre-existing conduction disease.
Use with caution in prior AV block or with PR-prolonging drugs; monitor ECG.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8
Atazanavir is hepatotoxic, especially in patients with hepatitis B or C; prior liver disease increases the risk of decompensation.
Monitor transaminases; consider alternatives in severe liver disease.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8
Atazanavir is used in pregnancy as part of HIV antiretroviral therapy; fetal exposure is accepted given the benefit of viral suppression.
Use in pregnancy as part of the antiretroviral regimen; the dose may need adjustment in the 3rd trimester.
Excreted into breast milk; in HIV infection breastfeeding is not recommended regardless of treatment.
Atazanavir lowers oestrogen/progestin levels — consider an additional method if a hormonal contraceptive is used.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
HIV-1 protease inhibitor (PI) that prevents the cleavage of gag and gag-pol protein precursors in the immature virion, blocking the maturation and infectivity of new virions. In combination with other antiretrovirals it reduces viral load and increases CD4 lymphocytes. Prolongs the PR interval and raises indirect bilirubin (benign jaundice).
Binds to the active site of HIV-1 protease, preventing cleavage of viral polyproteins — the resulting virions are immature and non-infectious. Pharmacokinetics are non-linear (greater than dose-proportional increases in AUC and Cmax between 200 and 800 mg/day), with a Tmax of ~2.5 hours and steady state at 4–8 days.
Atazanavir is rapidly absorbed (Tmax ~2.5 hours). Food increases bioavailability and reduces variability: a light meal increases AUC by 70% and Cmax by 57% relative to fasting. Serum protein binding is 86%, concentration-independent (albumin and alpha-1-acid glycoprotein).
Atazanavir is extensively metabolised in the liver, mainly by mono-oxygenation and dioxygenation (CYP3A4); minor pathways include glucuronidation, N-dealkylation and hydrolysis. It is a moderate CYP3A4 inhibitor and a substrate of the same enzyme and of P-glycoprotein.
The elimination half-life (t½) is ~7.9 hours with 400 mg once daily, increasing to ~18 hours when boosted with ritonavir 100 mg (300 mg/day). Steady state is reached between days 4 and 8, with ~2.3-fold accumulation.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
