REYATAZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REYATAZ (REYATAZ).
Atazanavir is an azapeptide HIV-1 protease inhibitor that 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 isoenzyme; also glucuronidated (UGT1A1). |
| Excretion | Reyataz (atazanavir) is primarily metabolized by the liver via CYP3A4. Approximately 79% of the dose is excreted in feces (as unchanged drug and metabolites), and 13% in urine (mostly as metabolites). Renal elimination of unchanged drug is negligible (<1%). |
| Half-life | The terminal elimination half-life of atazanavir in adults is approximately 7 hours when given with a boosted regimen (e.g., with ritonavir), and 6-8.5 hours without boosting. With food, absorption is enhanced, but half-life is not significantly altered. |
| Protein binding | Atazanavir is approximately 86% bound to human serum proteins (albumin and alpha-1-acid glycoprotein) over the concentration range of 0.1 to 10 µg/mL. |
| Volume of Distribution | The volume of distribution of atazanavir is approximately 22 L/kg (range 15-30 L/kg), indicating extensive tissue distribution and penetration into cells, including virus-containing cells. |
| Bioavailability | Oral bioavailability is increased by approximately 70% when taken with a light meal (300 kcal, 15 g fat) compared to fasting. Absolute bioavailability has not been determined, but relative bioavailability with food is well-established. |
| Onset of Action | Oral: Peak plasma concentrations are reached approximately 2-3 hours after administration. Clinical antiviral effect begins within days, but maximal virologic suppression typically occurs within 4-8 weeks of continuous therapy. |
| Duration of Action | The duration of antiviral effect lasts throughout the dosing interval (once daily). Consistent trough concentrations above the protein-adjusted IC95 are necessary to suppress HIV replication. Missed doses may lead to virologic breakthrough. |
Atazanavir 400 mg orally once daily with food, or atazanavir 300 mg orally once daily with ritonavir 100 mg orally once daily with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For treatment-naive patients with end-stage renal disease managed with hemodialysis, atazanavir 300 mg with ritonavir 100 mg once daily is recommended. Not recommended for treatment-experienced patients with renal impairment. |
| Liver impairment | Child-Pugh Class A: no dose adjustment. Child-Pugh Class B: reduce dose to atazanavir 300 mg once daily with ritonavir 100 mg once daily. Child-Pugh Class C: contraindicated. |
| Pediatric use | For pediatric patients weighing ≥15 kg: atazanavir powder or capsules dosed based on weight with ritonavir. Weight 15-24 kg: atazanavir 150 mg + ritonavir 80 mg once daily; 25-32 kg: atazanavir 200 mg + ritonavir 100 mg once daily; 33-39 kg: atazanavir 250 mg + ritonavir 100 mg once daily; ≥40 kg: atazanavir 300 mg + ritonavir 100 mg once daily. For patients unable to swallow capsules, use oral powder (50 mg packet) mixed with food. |
| Geriatric use | No specific dose adjustment. Use with caution due to age-related comorbidities, potential renal and hepatic impairment, and increased risk of QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REYATAZ (REYATAZ).
| Breastfeeding | Atazanavir is excreted into human breast milk at low levels; the milk-to-plasma ratio is approximately 0.13. The amount ingested by the infant is subtherapeutic and unlikely to cause adverse effects. However, because of the potential for HIV transmission through breastfeeding, HIV-infected women should not breastfeed their infants in accordance with public health guidelines. In uninfected mothers, the decision to breastfeed should consider the need for the drug and the potential for infant exposure. |
| Teratogenic Risk | Atazanavir (Reyataz) is classified as Pregnancy Category B. There is no evidence of teratogenicity in animal studies. In humans, data from the Antiretroviral Pregnancy Registry do not indicate an increased risk of major birth defects overall. However, cases of lactic acidosis and severe hepatomegaly with steatosis have been reported in pregnant women receiving protease inhibitors, including atazanavir. Hyperbilirubinemia may occur in neonates exposed in utero, but generally resolves without intervention. The drug is not recommended during the first trimester if alternatives exist due to limited data; use during second and third trimesters is considered acceptable if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to atazanavir or any component","Concomitant use with CYP3A4 substrates that have narrow therapeutic windows (e.g., alfuzosin, rifampin, ergot derivatives, oral midazolam, triazolam, lovastatin, simvastatin, St. John's wort, pimozide, indinavir, irinotecan)"]
| Precautions | ["Cardiac conduction abnormalities (PR interval prolongation)","Rash (including Stevens-Johnson syndrome)","Hyperbilirubinemia (due to UGT1A1 inhibition)","Nephrolithiasis/cholelithiasis","Hepatotoxicity","Diabetes mellitus/hyperglycemia","Hemophilia (increased bleeding)","Lipodystrophy","Immune reconstitution syndrome","Fat redistribution"] |
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| Fetal Monitoring | Monitoring should include complete blood count, liver function tests (especially bilirubin), renal function, glucose and lipid profiles, and viral load. During pregnancy, ultrasound for fetal growth assessment is recommended. Neonates should be monitored for hyperbilirubinemia and signs of lactic acidosis. Close observation for maternal hepatotoxicity and hyperbilirubinemia is warranted. |
| Fertility Effects | Atazanavir has not been associated with fertility impairment in animal studies. In humans, no specific adverse effects on male or female fertility have been reported. However, as with other antiretroviral agents, its use should be considered within the context of overall reproductive health. |