atazanavir
Brand: Reyataz, Evotaz (with cobicistat)
Prototype: darunavir
Drug Class: HIV protease inhibitor (PI)
Drug Family: antiretroviral
Subclass: azapeptide protease inhibitor
Organ Systems: infectious-disease
Mechanism of Action
Selectively inhibits HIV-1 protease; unlike most other PIs, atazanavir does not cause lipid elevations — it actually lowers LDL in some patients; once-daily dosing advantage; requires boosting with ritonavir or cobicistat; unique adverse effect: indirect hyperbilirubinemia via UGT1A1 inhibition.
HIV-1 protease
Indications
- HIV-1 infection (in combination ART with ritonavir or cobicistat boosting)
Contraindications
- atazanavir hypersensitivity
- concurrent drugs requiring CYP3A4/UGT1A1 for clearance with narrow TI (pimozide, cisapride, lovastatin, simvastatin)
- concurrent PPIs at standard doses (require gastric acid for absorption)
Adverse Effects
Common
- indirect hyperbilirubinemia/jaundice (benign — UGT1A1 inhibition; universal in UGT1A1*28/*28 homozygotes)
- nausea
- headache
Serious
- nephrolithiasis/cholelithiasis (crystallization of atazanavir in urine/bile)
- PR interval prolongation/heart block (first degree common; rarely clinically significant)
- hypersensitivity (including rash)
- metabolic effects less than other PIs
Pharmacokinetics (ADME)
| Absorption | requires food and gastric acid for absorption; PPIs can reduce atazanavir to undetectable levels — avoid or limit to omeprazole ≤20 mg equivalent |
| Distribution | widely distributed; 86% protein-bound |
| Metabolism | hepatic CYP3A4 (primary); also inhibits UGT1A1 (causes bilirubinemia) and CYP3A4 |
| Excretion | biliary/fecal (79%); renal (13%) |
| Half-life | 7–8 hours (boosted) |
| Onset | 2.5–3 hours |
| Peak | 2.5–3 hours |
| Duration | once-daily (boosted) |
| Protein Binding | 86% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| PPIs (omeprazole, pantoprazole, esomeprazole) | reduce gastric acid, reducing atazanavir absorption; avoid PPIs or limit; H2 blockers preferable | major |
| tenofovir | tenofovir reduces atazanavir AUC ~25%; must use ritonavir boosting when combined with tenofovir | major |
| simvastatin/lovastatin | CYP3A4 inhibition causes massive statin accumulation; rhabdomyolysis risk — contraindicated | major |
Nursing Considerations
- Administer with food and a substantial meal for absorption; counsel patients to avoid PPIs — even OTC omeprazole or pantoprazole significantly reduces drug levels.
- Instruct patients that yellowing of skin or eyes (jaundice) is expected from elevated indirect bilirubin via UGT1A1 inhibition — reassure that this is benign, not hepatotoxicity, and does not require stopping the drug.
- Monitor for nephrolithiasis symptoms — flank pain, hematuria; maintain adequate hydration to prevent atazanavir crystal deposition in urine.
- Obtain ECG if co-administering with drugs affecting cardiac conduction; first-degree AV block is common and usually asymptomatic.
Clinical Pearls
- Atazanavir's benign lipid profile (neutral effect on triglycerides, may actually lower total cholesterol) distinguishes it from other PIs, which universally raise lipids — making it preferable in patients with pre-existing cardiovascular risk.
- The indirect hyperbilirubinemia from atazanavir is a predictable, dose-dependent consequence of its inhibition of UGT1A1 — the same enzyme responsible for Gilbert's syndrome; patients who are UGT1A1*28/*28 homozygotes (Gilbert phenotype) will have more pronounced jaundice.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.