Atazanavir (atazanavir sulfate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Atazanavir sulfate, an antiretroviral agent, is a human immunodeficiency virus (HIV) protease inhibitor (PI).
Atazanavir, a synthetic azapeptide, inhibits replication of human immunodeficiency virus type 1 (HIV-1) by interfering with HIV protease. During HIV replication, HIV protease cleaves viral polypeptide products of the gag and gag-pol genes to form structural proteins of the virion core and essential viral enzymes. By interfering with the formation of these essential proteins and enzymes, atazanavir blocks maturation of the virus and causes formation of nonfunctional, immature noninfectious virions.
Atazanavir has some activity in vitro against HIV-2.
HIV-1 strains with reduced susceptibility to atazanavir can be produced in vitro and strains with reduced susceptibility to atazanavir have emerged during therapy with the drug. Varying degrees of cross-resistance occur among HIV protease inhibitors (PIs). Some HIV-1 isolates resistant to atazanavir may be cross-resistant to other HIV PIs (e.g., amprenavir (active metabolite of fosamprenavir), indinavir, lopinavir, nelfinavir, ritonavir, saquinavir).
Atazanavir is extensively metabolized by the hepatic cytochrome P-450 (CYP) enzyme system, principally CYP3A, and usually is administered with a pharmacokinetic enhancer (pharmacokinetic booster) to improve the pharmacokinetic profile of the drug. Atazanavir may be administered with low-dose ritonavir (ritonavir-boosted atazanavir) or with cobicistat (cobicistat-boosted atazanavir). Because ritonavir and cobicistat are potent inhibitors of CYP3A, concomitant administration with atazanavir results in increased peak plasma concentrations and area under the plasma concentration-time curve (AUC) of the HIV PI.
The antiretroviral activity of ritonavir-boosted atazanavir or cobicistat-boosted atazanavir is due to atazanavir.
Atazanavir is rapidly absorbed following oral administration. Peak plasma concentrations of atazanavir are attained in approximately 2.5 hours. When unboosted atazanavir is used, the drug demonstrates nonlinear pharmacokinetics with greater than dose- proportional increases in plasma concentrations and AUC.
Steady-state atazanavir concentrations following administration of unboosted atazanavir are attained between days 4-8, with an accumulation of approximately 2.3-fold.
Food increases bioavailability and reduces pharmacokinetic variability of oral atazanavir. Administration of a single 400-mg dose of unboosted atazanavir with a light meal increases the AUC by 70% and increases peak plasma concentrations by 57% compared with fasting; administration with a high-fat meal increases the AUC by 35%, but does not increase peak plasma concentrations. Administration of a single dose of ritonavir-boosted atazanavir (300 mg of atazanavir with 100 mg of ritonavir) with a light meal increases atazanavir AUC by 33% and increases peak plasma concentrations by 40% compared with fasting; administration with a high-fat meal does not affect atazanavir AUC.
Atazanavir is 86% bound to serum proteins; binding is independent of concentration. Atazanavir binds to both alpha-1-acid glycoprotein (89%) and albumin (86%). Low concentrations of atazanavir are attained in CSF and semen after oral administration.
Atazanavir is distributed into fetal umbilical cord blood in low concentrations. When ritonavir-boosted atazanavir was used in pregnant women, atazanavir concentrations in cord blood were approximately 12-19% of maternal plasma concentrations at delivery.
Atazanavir is extensively metabolized and eliminated in the liver. CYP3A is involved in metabolism of the drug. Following administration of unboosted atazanavir, approximately 79% of a dose is eliminated in feces and 13% is eliminated in urine as metabolites and unchanged drug.
The mean half-life of atazanavir is 6.5-7.9 hours at steady state in individuals receiving unboosted atazanavir (400 mg of atazanavir once daily) given with a light meal. Following administration of ritonavir-boosted atazanavir, the mean half-life of atazanavir at steady state is 8.6-18.1 hours.
Following administration of unboosted atazanavir, the AUC of the drug is increased 42% in adults with moderate to severe hepatic impairment (Child-Pugh class B and C) compared with healthy adults. The half-life of the drug is 12.1 hours in those with moderate to severe hepatic impairment.
USES: This drug is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life.
Atazanavir belongs to a class of drugs known as protease inhibitors. It may be given with certain other medications (such as cobicistat, ritonavir) to increase ("boost") the levels of atazanavir. This helps atazanavir work better.
Atazanavir is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor. Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor.
Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.
Generic name: atazanavir sulfate
Pronunciation: (A-ta-ZAN-a-vir)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Atazanavir
Indications
The following indications are listed for Atazanavir:
- Hiv Infection
Also known as: Human Immunodeficiency Virus Disease, Human Immunodeficiency Virus Infection.
Dosing
Atazanavir is commercially available as capsules or oral powder containing atazanavir sulfate; dosage is expressed in terms of atazanavir.
Atazanavir is used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Atazanavir is administered orally in conjunction with low-dose ritonavir (ritonavir-boosted atazanavir) or unboosted (i.e., without low-dose ritonavir) once daily with food.
If atazanavir is used concomitantly with certain drugs (e.g., antacids, didanosine, histamine H2-receptor antagonists), dosage adjustments may be needed and/or doses of atazanavir and the other drug may need to be given at separate times.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
When ritonavir-boosted atazanavir is used, consider the cautions, precautions, contraindications, and drug interactions associated with atazanavir and ritonavir.
Since ritonavir is a CYP3A inhibitor, initiation of ritonavir-boosted atazanavir in patients receiving drugs metabolized by CYP3A or initiation of drugs metabolized by CYP3A in patients already receiving ritonavir-boosted atazanavir, may increase plasma concentrations of the drugs metabolized by CYP3A. Initiation of drugs that inhibit CYP3A may increase concentrations of ritonavir-boosted atazanavir, and initiation of drugs that induce CYP3A may decrease concentrations of ritonavir-boosted atazanavir.
Interactions with ritonavir-boosted atazanavir resulting in greater exposures of concomitant medications may lead to clinically important adverse effects (including severe, life-threatening, or fatal events). Some interactions may result in clinically important adverse effects due to greater exposures to ritonavir-boosted atazanavir, or loss of therapeutic effect of ritonavir-boosted atazanavir and development of resistance.
Consider potential drug interactions prior to and during use of ritonavir-boostedatazanavir. Monitor patients for adverse reactions associated with other drugs used concomitantly with ritonavir-boosted atazanavir.
Additional drug interactions may exist for the fixed-dose combination of atazanavir and cobicistat (Evotaz(R)). See the full prescribing information for drug interactions of this combination product.
When atazanavir is used with ritonavir, consider the drug interactions associated with both atazanavir and ritonavir. The following drug interactions are based on studies using ritonavir-boosted atazanavir or unboosted atazanavir.
Additional drug interactions may exist for the fixed-dose combination of atazanavir and cobicistat (Evotaz(R)). See the full prescribing information for drug interactions of this combination product.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to atazanavir sulfate or any ingredient in the formulation.
*Concomitant use with drugs that are highly dependent on cytochrome P-450 (CYP) isoenzyme 3A (CYP3A) or uridine diphosphate-glucuronosyltransferase (UGT) 1A1 for clearance and for which elevated plasma concentrations of the interacting drugs are associated with serious and/or life-threatening events (see list below).
*Concomitant use with drugs that are strong inducers of CYP3A due to the potential for loss of therapeutic effect and development of resistance (see list below).
*The following drugs are contraindicated with atazanavir (with or without ritonavir, unless otherwise noted): alfuzosin, amiodarone (with ritonavir), quinidine (with ritonavir), carbamazepine, phenobarbital, phenytoin, rifampin, apalutamide, encorafenib, irinotecan, ivosidenib, lurasidone (with ritonavir), pimozide, oral triazolam, oral midazolam, dihydroergotamine, ergotamine, ergonovine, methylergonovine, cisapride, elbasvir/grazoprevir, glecaprevir/pibrentasvir, St. John's wort (Hypericum perforatum), lovastatin, simvastatin, lomitapide, sildenafil for the treatment of pulmonary arterial hypertension (Revatio(R)), indinavir, and nevirapine.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects (incidence >=2%) are headache, nausea, jaundice/scleral icterus, abdominal pain, rash, vomiting, diarrhea, insomnia, peripheral neurologic symptoms, dizziness, myalgia, depression, and fever.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Because of the risk of kernicterus, do not use atazanavir in neonates and infants <3 months of age. Safety, efficacy, and pharmacokinetic profile of atazanavir have not been established in infants <3 months of age. All contraindications, warnings, and precautions of atazanavir apply to pediatric patients.
Safety, efficacy, and pharmacokinetic profile of atazanavir have been evaluated in pediatric patients >=3 months of age weighing >=5 kg. Adverse effects reported in pediatric patients 6 to <18 years of age receiving atazanavir capsules were generally similar to those reported in adults. Adverse effects reported in pediatric patients weighing >=5 kg receiving atazanavir oral powder were generally similar to those reported in pediatric patients receiving the capsules.
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to atazanavir during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
Atazanavir has been evaluated in a limited number of women during pregnancy. Available human and animal data suggest that atazanavir does not increase the risk of major birth defects overall compared to the background rate. No treatment-related malformations were observed in rats and rabbits using dosages that resulted in atazanavir exposures 0.7-1.2 times those reported with the usual human dosage of ritonavir-boosted atazanavir (300 mg of atazanavir once daily with ritonavir 100 mg once daily).
Based on prospective reports from the APR of approximately 1600 live births following exposure to atazanavir-containing antiretroviral regimens during pregnancy (including 1037 first-trimester exposures), there was no difference in the rate of overall birth defects in those exposed to atazanavir-containing regimens compared with the estimated background risk of major birth defects (2-4% in the US population).
Dosage adjustments may be necessary in certain pregnant women. Lactic acidosis, sometimes fatal, and symptomatic hyperlactatemia have occurred in pregnant patients receiving atazanavir in conjunction with NRTIs. Hyperbilirubinemia has occurred in pregnant patients receiving atazanavir. Advise pregnant patients of the potential risks of lactic acidosis syndrome and hyperbilirubinemia.
Closely monitor postpartum women for adverse effects during the first 2 months after delivery since atazanavir concentrations and AUC may be increased approximately 28-43% during the postpartum period (4-12 weeks).
Atazanavir is distributed into human milk. It is not known whether atazanavir affects human milk production. Atazanavir is distributed into milk in rats and was associated with neonatal growth retardation that reversed after weaning.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The manufacturer makes no specific dosage recommendations for geriatric patients. Exercise caution in administration and monitoring because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
Experience in patients >=65 years of age is insufficient to determine whether they respond differently to atazanavir than younger adults. Exercise caution in administration and monitoring because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease or drug therapy in geriatric patients.
No clinically important differences in pharmacokinetics of atazanavir have been reported in those >65 years of age compared with younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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