Atazanavir

Pharmacologic interaction with bepridil (potential for serious and/or life-threatening adverse effects). Concomitant use of bepridil and atazanavir not recommended.

Pharmacokinetic interaction with antiarrhythmic agents (i.e., amiodarone, systemic lidocaine, quinidine). Potential for serious and/or life-threatening adverse effects. Monitor plasma concentrations of these antiarrhythmic agents if used concomitantly with atazanavir.

Potential pharmacokinetic interaction (increased plasma concentration of the tricyclic antidepressant). Potential for serious and/or life-threatening adverse effects. Monitor plasma concentrations of these tricyclic antidepressants agents if used concomitantly with atazanavir.

Pharmacokinetic interaction with rifampin (substantial decrease (90%) in the peak plasma concentration and area under the concentration-time curve (AUC) of HIV protease inhibitors). Concomitant use of atazanavir and rifampin not recommended.

For more Interactions (Complete) data for ATAZANAVIR (34 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3.8X10+7(SRC), determined from a structure estimation method(2), indicates that atazanavir is expected to be immobile in soil(SRC). Volatilization of atazanavir from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.6X10-32 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Atazanavir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.0X10-26 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3.8X10+7(SRC), determined from a structure estimation method(2), indicates that atazanavir is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.6X10-32 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 7.4(SRC), from an estimated log Kow of 2.9(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis may occur however the predicted rate indicates that the reaction would be very slow with half lives corresponding to 10,000 and 100,000 years for pH 8 and 7, respectively(8). These estimated rates suggest that hydrolysis is not expected to be an important fate process. Biodegradation data were not available(SRC,2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), atazanavir, which has an estimated vapor pressure of 1.0X10-26 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the atmosphere. Particulate-phase atazanavir may be removed from the air by wet and dry deposition(SRC). Based on other biphenyl compounds(3), atazanavir is not expected to absorb at >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Common adverse effects of atazanavir include hyperbilirubinemia (35% to 49% in adults and 16% in children), rash (up to 21%), hypercholesterolemia (6% to 25%), hyperamylasemia (14% to 33%), jaundice (5% to 9% in adults and 13% to 15% in children), nausea (3% to 14%), cough (21% in children), and fever (2% in adults and 18% to 19% in children). Severe adverse effects include Stevens-Johnson syndrome, toxic skin eruptions, erythema multiforme, angioedema, cholecystitis, pancreatitis, interstitial nephritis, diabetic ketoacidosis, and AV block. Additional potential adverse effects include nephrolithiasis, cholelithiasis, hyperlipidemia, hypertriglyceridemia, bleeding, pancreatitis, exacerbation of diabetes mellitus or hyperglycemia, and lactic acidosis when used in combination with nucleoside analogs.

Currently, no specific antidote exists for atazanavir toxicity. Patients should receive symptomatic and supportive care from healthcare staff while regularly monitoring their vital signs and looking for signs of respiratory distress. Electrocardiogram monitoring of the patient is recommended, as atazanavir may exacerbate AV block due to PR interval prolongation. In cases where a simultaneous overdose with nucleoside reverse transcriptase inhibitors is suspected, clinicians should carefully monitor patients for symptoms of lactic acidosis.

Using a structure estimation method based on molecular connectivity indices(1), the Koc for atazanavir can be estimated to be 3.8X10+7(SRC). According to a classification scheme(2), this estimated Koc value suggests that atazanavir is expected to be immobile in soil.

/SIGNS AND SYMPTOMS/ At high doses that lead to high drug exposures, jaundice due to indirect (unconjugated) hyperbilirubinemia (without associated liver function test changes) or PR interval prolongation may be observed.

/SIGNS AND SYMPTOMS/ ... Stevens-Johnson syndrome and erythema multiforme have been reported in patients receiving atazanavir.

/CASE REPORTS/ A single self-administered overdose of 29.2 g of /atazanavir/ in an HIV-infected patient (73 times the recommended dose) was associated with asymptomatic bifascicular block and PR interval prolongation. These events resolved spontaneously.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

atazanavir

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

An estimated BCF of 7.4 was calculated for atazanavir(SRC), using an estimated log Kow of 2.9(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for atazanavir is estimated as 3.6X10-32 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that atazanavir is expected to be essentially nonvolatile from moist soil(SRC) and water surfaces(2). Atazanavir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.0X10-26 mm Hg(SRC), determined from a fragment constant method(3).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl atazanavir sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Atazanavir Sulfate/

Human immunodeficiency virus (HIV) infection (treatment). Atazanavir sulfate is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. /Atazanavir Sulfate/

Medication

Use (kg; approx.) in Germany (2009): >500

While data specific to atazanavir were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).