ATAZANAVIR SULFATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATAZANAVIR SULFATE (ATAZANAVIR SULFATE).
Atazanavir is an azapeptide HIV-1 protease inhibitor. It selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, preventing formation of mature virions.
| Metabolism | Extensively metabolized in the liver via CYP3A4; also undergoes glucuronidation. It is a substrate of P-glycoprotein. |
| Excretion | Biliary/fecal: ~79% as unchanged drug; renal: ~13% (including <1% unchanged). |
| Half-life | Terminal elimination half-life: ~6.5 to 7 hours; supports once-daily dosing. |
| Protein binding | ~86% bound to human serum albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Approximately 1.1 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: ~60–68% (enhanced with food, especially light meal). |
| Onset of Action | Oral: Antiviral effect within 4–7 days with consistent administration. |
| Duration of Action | Approximately 24 hours; maintained via once-daily dosing due to trough concentrations above IC90. |
300 mg orally once daily with ritonavir 100 mg orally once daily, or 400 mg orally once daily without ritonavir (when used alone).
| Dosage form | CAPSULE |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl >=20 mL/min). Not recommended for use in treatment-experienced patients with end-stage renal disease (CrCl <20 mL/min) not on hemodialysis. For hemodialysis patients, use atazanavir 300 mg boosted with ritonavir 100 mg once daily. |
| Liver impairment | Child-Pugh Class A: 400 mg orally once daily without ritonavir. Child-Pugh Class B: Reduce dose to 300 mg orally once daily without ritonavir. Child-Pugh Class C: Not recommended. |
| Pediatric use | Weight-based dosing for patients ≥3 months and ≥5 kg: For patients ≥35 kg: 300 mg with ritonavir 100 mg once daily. For weight 15 to <35 kg: atazanavir 200 mg with ritonavir 100 mg once daily. For weight 5 to <15 kg: atazanavir 150 mg/m² (max 200 mg) with ritonavir 80 mg/m² once daily. Dosing in premature infants not established. |
| Geriatric use | No specific dose adjustment is recommended; caution due to potential for increased risk of PR interval prolongation and renal impairment. Monitor renal function and ECG. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATAZANAVIR SULFATE (ATAZANAVIR SULFATE).
| Breastfeeding | Atazanavir is excreted in human milk. M/P ratio not established. Due to potential for HIV transmission, adverse effects in the infant (hyperbilirubinemia, kernicterus), and unknown viral suppression, breastfeeding is contraindicated in HIV-infected mothers. |
| Teratogenic Risk | Pregnancy category B. In preclinical studies, no evidence of teratogenicity. First trimester: No increased risk of major birth defects based on human data. Second/third trimester: Case reports of hyperbilirubinemia and kernicterus in neonates; avoid use near term due to risk of neonatal hyperbilirubinemia. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with drugs highly dependent on CYP3A4 for clearance (e.g., alfuzosin, amiodarone, ergot derivatives, lovastatin, simvastatin, rifampin, St. John's wort, certain benzodiazepines)","Concomitant use with nevirapine (atazanavir levels decreased)","Concomitant use with indinavir (risk of hyperbilirubinemia)","Patients with severe hepatic impairment (Child-Pugh class C)","Known hypersensitivity to atazanavir or any component"]
| Precautions | ["Cardiac conduction abnormalities (PR interval prolongation; use with caution with other drugs that prolong PR interval)","Rash (usually mild to moderate; Stevens-Johnson syndrome rare)","Hepatotoxicity (especially in patients with hepatitis B or C co-infection)","Nephrolithiasis and cholelithiasis (crystalluria, gallstones)","Hyperbilirubinemia (unconjugated; benign but may cause jaundice)","Immune reconstitution syndrome","Fat redistribution/accumulation","Hemophilia (spontaneous bleeding reported)","Diabetes mellitus/hyperglycemia (new onset or exacerbation)","Decreased bone mineral density"] |
| Food/Dietary |
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| Fetal Monitoring | Maternal: Hepatic function, bilirubin, LFTs, glucose, and HIV viral load. Fetal: Ultrasound for growth restriction and anomalies; neonatal bilirubin monitoring after delivery. |
| Fertility Effects | No significant effects on fertility reported in animal studies. Human data insufficient to determine impact on male or female fertility. |
| Take with food (light meal or snack) to enhance absorption. Avoid concomitant use with St. John's wort, garlic supplements, or high-fat meals (may reduce exposure). No specific foods contraindicated, but consistency in administration with food is recommended. |
| Clinical Pearls | Administer with food to increase absorption and reduce gastrointestinal intolerance. Atazanavir requires acidic gastric pH for solubility; avoid concomitant use with proton pump inhibitors. Use with tenofovir disoproxil fumarate may decrease atazanavir concentrations; consider boosting with ritonavir or cobicistat. Monitor for indirect hyperbilirubinemia (benign, but may cause jaundice/scleral icterus). Atazanavir may prolong PR interval; use caution with pre-existing conduction abnormalities. Unboosted atazanavir should not be used in treatment-experienced patients with prior virologic failure. |
| Patient Advice | Take this medication with food, preferably a meal or snack, to improve absorption and reduce stomach upset. · Do not miss doses; if you miss a dose within 6 hours of the usual time, take it with food. If more than 6 hours late, skip the missed dose and take the next dose at the regular time. · This drug may cause a harmless yellowing of the skin or eyes due to increased bilirubin; consult your healthcare provider if it becomes bothersome. · Avoid taking antacids or medications for heartburn (especially proton pump inhibitors) unless prescribed, as they reduce the effectiveness of atazanavir. · Inform all healthcare providers that you are taking atazanavir, as it can interact with many medications, including hormonal contraceptives, statins, and certain antiarrhythmics. · Atazanavir does not cure HIV or prevent transmission; continue to practice safe sex and avoid sharing needles. · Report any signs of rash, abnormal heartbeat, or severe nausea/vomiting to your healthcare provider immediately. |