Antiretroviral, HIV protease inhibitor
Brand names: Reyataz
Updated · Methodology
Second line
Atazanavir is a second-line HIV-1 protease inhibitor. GeSIDA 2024 places it as an option when dolutegravir or bictegravir are not tolerated, usually combined with ritonavir or cobicistat as a booster plus 2 NRTIs. Advantage over other protease inhibitors – minimal lipid impact. Main limitation – gastric acid dependent absorption.
Sources
ICD-10: B20 · ICD-11: 1C62
Competitive inhibitor of HIV-1 protease, the enzyme that cleaves viral polyproteins into functional proteins. Without cleavage, virions remain immature and non-infectious. Metabolised by CYP3A4 and itself inhibits CYP3A4 and UGT1A1. Absorption is gastric acid dependent – PPIs reduce bioavailability substantially.
HIV pregnancy registry shows no increase in birth defects. Can be used in pregnancy when ART is needed.
Breastfeeding by women with HIV is not recommended in Spain regardless of regimen.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
7 pairs found. Sorted from critical to minor.
Mechanism
CYP3A4 inhibition – fatal ergotism. Fatal cases reported.
Symptoms
Limb ischaemia, stroke.
Management
Combination contraindicated.
Mechanism
CYP3A4 inhibition by atazanavir raises pimozide – torsades de pointes.
Symptoms
QT prolongation, syncope.
Management
Combination contraindicated.
Mechanism
Strong CYP3A4 induction – atazanavir falls 80%. ART failure.
Symptoms
Rising viral load.
Management
Combination contraindicated.
Mechanism
Atazanavir inhibits CYP3A4. Simvastatin rises 10+ fold – fatal rhabdomyolysis.
Symptoms
Myalgia, dark urine within 5-10 days.
Management
Combination contraindicated. Switch to pravastatin or rosuvastatin.
Sources
Mechanism
CYP3A4 clears ticagrelor, and atazanavir inhibits this enzyme (atazanavir SmPC, , section 4.5). The ticagrelor SmPC classes atazanavir as a strong CYP3A4 inhibitor and expects the same effect as with ketoconazole. With ketoconazole, ticagrelor Cmax rose 2.4-fold and AUC 7.3-fold, while the active metabolite fell by 89% (Cmax) and 56% (AUC) (Brilique SmPC, EMA, section 4.5). Ticagrelor acts on platelets on its own, without the metabolite, so the antiplatelet effect and its adverse reactions rise with its concentration. The labels describe no effect of ticagrelor on atazanavir. When atazanavir is boosted with ritonavir, the booster is itself a strong CYP3A4 inhibitor and also appears in the ticagrelor contraindications (Brilique SmPC, EMA, section 4.3).
Symptoms
The main risk is bleeding: bruising, nosebleeds, blood in urine or stool, gastrointestinal bleeding and, at worst, intracranial bleeding. The second typical sign of excess ticagrelor is dyspnea: the ticagrelor label links strong CYP3A4 inhibitors directly to a higher risk of dyspnea, bleeding and other adverse events (section 7.1). The atazanavir SmPC () warns of a possible increase in the antiplatelet activity of ticagrelor (section 4.5).
Management
The combination is contraindicated: the ticagrelor SmPC bars it with strong CYP3A4 inhibitors and names atazanavir explicitly (Brilique SmPC, , sections 4.3 and 4.5). The atazanavir labels are softer: "not recommended" because of a possible increase in antiplatelet activity (atazanavir SmPC, EMA, section 4.5; Reyataz prescribing information, , section 7). The FDA ticagrelor label says to avoid strong CYP3A4 inhibitors including atazanavir (section 7.1). The strictest document wins, and in Spain the ban applies. For a patient on atazanavir who needs a P2Y12 inhibitor after an acute coronary syndrome, choose a different drug. Clopidogrel with atazanavir is also not recommended because its effect may weaken, while prasugrel needs no dose adjustment according to the atazanavir label (atazanavir SmPC, EMA, section 4.5; FDA, section 7). Whether prasugrel suits the individual patient is a question for its own label. If the patient is already taking both, do not drop ticagrelor without a replacement: stopping an antiplatelet drug in coronary artery disease raises the risk of myocardial infarction, stroke and death (Brilinta prescribing information, FDA, section 5.2). Plan the switch at once, and until then keep the higher risk of bleeding and dyspnea in mind (Brilinta, FDA, section 7.1). Investigate new, prolonged or worsening dyspnea on ticagrelor, and if the patient cannot tolerate it, stop ticagrelor (Brilique SmPC, EMA, section 4.4).
Sources
Mechanism
Atazanavir inhibits CYP3A4. Atorvastatin rises 8-fold – rhabdomyolysis risk.
Symptoms
Myalgia, weakness, dark urine, rising CK within 5-10 days.
Management
Cap atorvastatin at 10 mg/day. Better – pravastatin 40 mg.
Sources
Mechanism
Atazanavir dissolves and is absorbed less well when stomach acidity falls, and omeprazole suppresses acid secretion. Omeprazole 40 mg daily cut exposure to ritonavir-boosted atazanavir by 75%, and raising atazanavir to 400 mg did not make up for it. Without ritonavir, exposure fell by 94%. As a result, HIV treatment may lose virologic response and the virus may develop resistance.
Symptoms
No outward signs; the problem shows up in lab tests: HIV viral load rises on treatment, and the virus may become resistant to atazanavir.
Management
The combination is not recommended (omeprazole label; atazanavir label, European Medicines Agency ()). If a proton pump inhibitor cannot be avoided, raise atazanavir to 400 mg with ritonavir 100 mg, keep omeprazole at no more than 20 mg a day and closely monitor the response to treatment, mainly viral load (omeprazole label; atazanavir label, EMA). Taking the drugs 12 hours apart does not prevent the drop in atazanavir levels (atazanavir label, EMA). For atazanavir without ritonavir, the label also advises against proton pump inhibitors (atazanavir label, EMA). The US Food and Drug Administration () does not recommend the combination in treatment-experienced patients; in treatment-naive patients it allows no more than omeprazole 20 mg taken about 12 hours before atazanavir 300 mg with ritonavir 100 mg (atazanavir FDA label). If acid suppression is needed, the atazanavir label allows H2-receptor antagonists with a dose limit: with atazanavir 300 mg plus ritonavir 100 mg and no tenofovir, no more than the equivalent of famotidine 20 mg twice daily (atazanavir label, EMA).
Sources
Verbatim lines from the interaction sections, in the language of the label
«CONTRAINDICATIONS: Antiarrhythmics Amiodarone (with ritonavir), quinidine (with ritonavir)»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Anticonvulsants Carbamazepine, phenobarbital, phenytoin»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: GI Motility Agent Cisapride»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Ergot Derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Ergot Derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Herbal Products St. John’s wort ( Hypericum perforatum )»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Lipid-Modifying Agents: Lomitapide, lovastatin, simvastatin»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Phosphodiesterase-5 (PDE-5) Inhibitor Sildenafil b when dosed as REVATIO ® for the treatment of pulmonary arterial hypertension»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Anticonvulsants Carbamazepine, phenobarbital, phenytoin»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Anticonvulsants Carbamazepine, phenobarbital, phenytoin»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Antipsychotics Lurasidone (with ritonavir), pimozide»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Antiarrhythmics Amiodarone (with ritonavir), quinidine (with ritonavir)»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Lipid-Modifying Agents: Lomitapide, lovastatin, simvastatin»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Anticonvulsants Carbamazepine, phenobarbital, phenytoin»FDA, section 4 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: rivaroxaban apixaban Atazanavir with ritonavir ↑ rivaroxaban Atazanavir ↑ rivaroxaban Atazanavir with ritonavir ↑ apixaban Atazanavir…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: atorvastatin, rosuvastatin ↑ atorvastatin ↑ rosuvastatin Titrate atorvastatin dose carefully and use the lowest necessary dose…»FDA, section 7 · Open on DailyMed
«CONTRAINDICATIONS: Benzodiazepines Orally administered midazolam a , triazolam»FDA, section 4 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Macrolide antibiotics: clarithromycin ↑ clarithromycin ↓ 14-OH clarithromycin ↑ atazanavir Increased concentrations of clarithromycin…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Antiplatelets ticagrelor clopidogrel ↑ ticagrelor ↓ clopidogrel active metabolite Coadministration with ticagrelor is not recommended…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Antigout: colchicine ↑ colchicine The coadministration of atazanavir with colchicine in patients with renal or hepatic impairment is…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Corticosteroids: dexamethasone and other corticosteroids (all routes of administration) ↓ atazanavir ↑ corticosteroids…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs): efavirenz ↓ atazanavir In HIV-treatment-naive adult patients: If atazanavir…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: H 2 -Receptor antagonists ↓ atazanavir Coadministration may result in loss of virologic response and development of resistance. In…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Atazanavir with ritonavir ↑ fluticasone With concomitant use of fluticasone propionate and atazanavir with ritonavir systemic…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Atazanavir with ritonavir ↑ fluticasone With concomitant use of fluticasone propionate and atazanavir with ritonavir systemic…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Antiarrhythmics: amiodarone, quinidine amiodarone, bepridil, lidocaine (systemic), quinidine ↑ amiodarone, bepridil, lidocaine…»FDA, section 7 · Open on DailyMed
«Administración con atazanavir, saquinavir, daclatasvir, dasabuvir, dolutregravir, paritaprevir, ombitasvir, ledipasvir, simeprevir, sofosbuvir. (ver sección 4.5).»AEMPS, section 4.3 · Open on CIMA
«La administración concomitante de ticagrelor con inhibidores potentes del CYP3A4 (p. ej., ketoconazol, claritromicina, nefazodona, ritonavir y atazanavir), ya que la administración concomitante puede…»AEMPS, section 4.3 · Open on CIMA
«Inhibidores de la CYP3A4: Los inhibidores potentes de la CYP3A4 han demostrado que producen concentraciones notablemente elevadas de atorvastatina (ver Tabla 1 y la información específica a…»AEMPS, section 4.5 · Open on CIMA
«Atazanavir: Claritromicina y atazanavir son sustratos e inhibidores del CYP3A y hay evidencias de interacción bidireccional entre ellos. La co-administración de claritromicina (500 mg 2 veces al día)…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Atazanavir Use With Caution Atazanavir: When clarithromycin is co-administered with atazanavir, the dose of clarithromycin should be decreased by 50% [see Clinical Pharmacology…»FDA, section 7 · Open on DailyMed
«Inhibidores nucleosídicos o nucleotídicos de la transcriptasa inversa (ITINss): La combinación de darunavir administrado de forma conjunta con dosis bajas de ritonavir y atazanavir se puede…»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Protease inhibitor: Atazanavir ↓ atazanavir * Treatment –naïve patients : When co-administered with efavirenz tablets , the…»FDA, section 7 · Open on DailyMed
«Inhibidores de la Proteasa: Para el atazanavir y el nelfinavir, se ha comunicado una disminución de los niveles plasmáticos cuando se administran junto con omeprazol, por lo tanto, no se recomienda…»AEMPS, section 4.5 · Open on CIMA
«Inhibidores potentes del CYP3A4: Después de la inhibición del CYP3A4 mediante la administración concomitante de 200 mg de ketoconazol dos veces al día, la C max y el AUC del metabolito activo de…»AEMPS, section 4.5 · Open on CIMA
«Inhibitors of Cytochrome P450 3A4: Fluticasone propionate is a substrate of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole…»FDA, section 7 · Open on DailyMed
«Inhibitors of Cytochrome P450 3A4: Fluticasone propionate is a substrate of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole…»FDA, section 7 · Open on DailyMed
«Inhibidores de la proteasa del VIH: No se recomienda la administración conjunta de lansoprazol con inhibidores de la proteasa del VIH, tales como atazanavir y nelfinavir, debido a que se produce una…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Intervention: Rilpivirine-containing products: Concomitant use with lansoprazole delayed-release capsules is contraindicated [see Contraindications ( 4 )]. See prescribing…»FDA, section 7 · Open on DailyMed
«Nelfinavir, atazanavir: La administración concomitante de omeprazol con nelfinavir está contraindicada (ver sección 4.3). La administración concomitante de omeprazol (40 mg una vez al día) redujo la…»AEMPS, section 4.5 · Open on CIMA
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Atazanavir is evaluated for the following indications with varying evidence strength: HIV infection (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Atazanavir (≥ 1 in 100): Hyperbilirubinaemia (without hepatocellular injury), Scleral icterus, Nausea, Rash, Headache. See the Safety section for uncommon and serious reactions.
HIV pregnancy registry shows no increase in birth defects. Can be used in pregnancy when ART is needed.
Breastfeeding by women with HIV is not recommended in Spain regardless of regimen.
Atazanavir is contraindicated in: PPI co-administration (omeprazole, esomeprazole) – ART failure; Simvastatin, lovastatin – rhabdomyolysis; Pimozide, ergotamine, oral midazolam, cisapride, rifampicin, St John's wort; Severe hepatic impairment. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Brivudine, Darunavir, Efavirenz, Entecavir, Inosine pranobex, Oseltamivir, Umifenovir, Famciclovir