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# Atazanavir
## Overview
Atazanavir is a protease inhibitor used in the treatment of human immunodeficiency virus (HIV) infection. It is typically part of a combination antiretroviral therapy (ART) regimen.
## Primary Indications
* Treatment of HIV-1 infection in adults and pediatric patients.
## Adult Dosing
* **For treatment-naive patients:** 300 mg orally once daily, coadministered with ritonavir 100 mg orally once daily, and with tenofovir disoproxil fumarate (TDF) 300 mg orally once daily and emtricitabine 200 mg orally once daily (or a single tablet regimen containing these components).
* **For treatment-experienced patients:** 300 mg orally once daily, coadministered with ritonavir 100 mg orally once daily, and with another antiretroviral agent.
* **Alternative regimen (without ritonavir, in specific populations):** 400 mg orally once daily, coadministered with tenofovir disoproxil fumarate (TDF) 300 mg orally once daily and emtricitabine 200 mg orally once daily. This regimen is generally not preferred due to lower barrier to resistance and higher incidence of hyperbilirubinemia.
## Pediatric Dosing
* **Ages 6 months to less than 17 years:** Dosing is based on weight and coadministration with ritonavir.
* **<15 kg:** 4 mg/kg orally once daily with ritonavir 1 mg/kg orally once daily.
* **15 to <25 kg:** 6 mg/kg orally once daily with ritonavir 1.5 mg/kg orally once daily.
* **25 to <35 kg:** 8 mg/kg orally once daily with ritonavir 2 mg/kg orally once daily.
* **≥35 kg:** 10 mg/kg orally once daily with ritonavir 2.5 mg/kg orally once daily (max 300 mg atazanavir, 100 mg ritonavir).
* *Note: Dosing of atazanavir alone without ritonavir in pediatric patients is not recommended.*
## Dose Adjustments
* **Renal Impairment:** No dose adjustment is needed for mild to moderate renal impairment. Use with caution in severe renal impairment or end-stage renal disease due to lack of data.
* **Hepatic Impairment:** Use with caution in patients with mild to moderate hepatic impairment. Use is contraindicated in severe hepatic impairment.
* **Coadministration with other drugs:** Dose adjustments are critical based on interactions. See Key Drug Interactions.
## Contraindications
* Concurrent use with sofosbuvir/velpatasvir/voxilaprevir.
* Concurrent use with rifampin.
* Concurrent use with St. John's wort.
* Concurrent use with certain HMG-CoA reductase inhibitors (e.g., simvastatin, lovastatin).
* Known hypersensitivity to atazanavir or any of its components.
* Severe hepatic impairment.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal pain, headache, rash, hyperbilirubinemia (jaundice, scleral icterus).
* **Serious:** Hepatotoxicity, severe skin reactions (including Stevens-Johnson syndrome), QT prolongation, nephrolithiasis (kidney stones), cholelithiasis (gallstones), fat redistribution, immune reconstitution inflammatory syndrome (IRIS).
## Key Drug Interactions
* **CYP3A4 Inducers:** Drugs that induce CYP3A4 (e.g., rifampin, St. John's wort, carbamazepine, phenytoin, phenobarbital) can significantly decrease atazanavir plasma concentrations, leading to loss of virologic response. Concurrent use is contraindicated with rifampin and St. John's wort.
* **CYP3A4 Inhibitors:** Ritonavir is commonly coadministered to boost atazanavir levels and allows for once-daily dosing. Other CYP3A4 inhibitors can also increase atazanavir levels and may require dose adjustments.
* **Drugs dependent on CYP3A4 for clearance:** Atazanavir is a moderate CYP3A4 inhibitor. Coadministration with drugs metabolized by CYP3A4 may increase the exposure of these drugs (e.g., certain statins, calcium channel blockers, benzodiazepines). Use with simvastatin and lovastatin is contraindicated. Use with atorvastatin may require dose reduction.
* **Gastric Acid Suppressants:** Antacids, H2 receptor antagonists, and proton pump inhibitors (PPIs) can decrease atazanavir absorption.
* Antacids: Separate dosing by at least 2 hours.
* H2 receptor antagonists: Administer atazanavir at least 10 hours after famotidine or atazanavir 400 mg + ritonavir 100 mg at least 10 hours after famotidine.
* PPIs: Administer atazanavir 400 mg + ritonavir 100 mg at least 12 hours before or 1-2 hours after the PPI. If taking atazanavir 300 mg + ritonavir 100 mg, administer at least 12 hours before PPI.
* **Emtricitabine/TDF/TAF:** Commonly used in combination regimens.
* **Didanosine:** Coadministration can increase didanosine AUC; separate dosing and monitor for toxicity.
* **Tenofovir Alafenamide (TAF):** Atazanavir can increase TAF concentrations.
## Monitoring
* HIV viral load and CD4 count.
* Liver function tests (LFTs), particularly in patients with pre-existing liver disease or co-infection with hepatitis B or C.
* Renal function.
* Lipid panels.
* Bilirubin levels.
* Signs and symptoms of hepatotoxicity, rash, kidney stones, and gallstones.
## Clinical Pearls
* Atazanavir should be taken with food to enhance absorption.
* It is crucial to coadminister atazanavir with ritonavir (or sometimes cobicistat) to boost plasma concentrations and improve efficacy, especially in treatment-experienced patients. This also helps overcome the lower barrier to resistance of atazanavir.
* The incidence of hyperbilirubinemia is higher when atazanavir is not boosted with ritonavir.
* Monitor for drug interactions closely, as atazanavir is a moderate inhibitor of CYP3A4.
* Ensure adequate hydration to reduce the risk of nephrolithiasis.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions. Dosing and management may vary based on individual patient factors and local protocols.
