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EVOTAZ (Atazanavir Or Cobicistat) to Pregnant Rats and Rabbits (See Data)

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EVOTAZ (Atazanavir Or Cobicistat) to Pregnant Rats and Rabbits (See Data) HIGHLIGHTS OF PRESCRIBING INFORMATION • Assess creatinine clearance (CLcr) before initiating treatment. Consider These highlights do not include all the information needed to use EVOTAZ alternative medications that do not require dosage adjustments in patients safely and effectively. See full prescribing information for EVOTAZ. with renal impairment. (5.3) • When cobicistat, a component of EVOTAZ, is used in combination with a EVOTAZ (atazanavir and cobicistat) tablet, for oral use tenofovir disoproxil fumarate (tenofovir DF)-containing regimen, cases of Initial U.S. Approval: 2015 acute renal failure and Fanconi syndrome have been reported. (5.4) • When used with tenofovir DF, assess urine glucose and urine protein at ---------------------------RECENT MAJOR CHANGES--------------------------­ baseline and monitor CLcr, urine glucose, and urine protein. Monitor serum Indications and Usage phosphorus in patients with or at risk for renal impairment. Coadministration Indications (1.1) 07/2020 with tenofovir DF is not recommended in patients with CLcr below 70 Dosage and Administration mL/min or in patients also receiving a nephrotoxic agent. (5.4) Laboratory Testing Prior to Initiation and During • Chronic kidney disease has been reported during postmarketing surveillance Treatment with EVOTAZ (2.1) 04/2020 in patients with HIV-1 infection treated with atazanavir, with or without Recommended Dosage (2.2) 07/2020 ritonavir. Consider alternatives in patients at high risk for renal disease or Not Recommended During Pregnancy (2.5) 04/2020 with preexisting renal disease. Monitor renal laboratory tests prior to therapy Contraindications (4) 04/2020 and during treatment with EVOTAZ. Consider discontinuation of EVOTAZ Warnings and Precautions in patients with progressive renal disease. (5.5) Immune Reconstitution Syndrome (5.11) 07/2020 • Nephrolithiasis and cholelithiasis have been reported. Consider temporary interruption or discontinuation. (5.6, 6) --------------------------INDICATIONS AND USAGE---------------------------­ • Hepatotoxicity: Patients with hepatitis B or C coinfection are at risk of EVOTAZ is a two-drug combination of atazanavir, a human immunodeficiency increased transaminases or hepatic decompensation. Monitor hepatic virus (HIV-1) protease inhibitor, and cobicistat, a CYP3A inhibitor indicated laboratory tests prior to therapy and during treatment. (2.5, 5.7, 8.7) for use in combination with other antiretroviral agents for the treatment of • Antiretrovirals that are not recommended: EVOTAZ is not recommended HIV-1 infection in adults and pediatric patients weighing at least 35 kg. (1) for use with ritonavir or products containing ritonavir, or in combination with other antiretroviral drugs that require CYP3A inhibition to achieve adequate Limitations of Use exposures (e.g., other protease inhibitors and elvitegravir). (5.9) Use of EVOTAZ in treatment-experienced patients should be guided by the • Hyperbilirubinemia: Most patients experience asymptomatic increases in number of baseline primary protease inhibitor resistance substitutions. (1) indirect bilirubin, which is reversible upon discontinuation. If a concomitant ------------------------DOSAGE AND ADMINISTRATION---------------------­ transaminase increase occurs, evaluate for alternative etiologies. (5.10, 6) • Pretreatment testing: Renal laboratory testing should be performed in all • Patients receiving EVOTAZ may develop immune reconstitution syndrome patients prior to initiation of EVOTAZ and continued during treatment with (5.11), new onset or exacerbations of diabetes mellitus/hyperglycemia (5.12, EVOTAZ. Hepatic testing should be performed in patients with underlying 6), and redistribution/accumulation of body fat (5.13). liver disease prior to initiation of EVOTAZ and continued during treatment • Hemophilia: Spontaneous bleeding may occur and additional factor VIII with EVOTAZ. (2.1) may be required. (5.14) • Recommended dosage: One tablet once daily, taken orally with food in adults -------------------------------ADVERSE REACTIONS-----------------------------­ and pediatric patients weighing at least 35 kg. (2.2) Most common adverse reactions seen with atazanavir coadministered with • Renal impairment: EVOTAZ is not recommended for use in treatment- cobicistat (greater than 5%, Grades 2-4) are jaundice and rash. (6.1) experienced patients with end-stage renal disease managed with hemodialysis. (2.3, 8.6) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers • Hepatic impairment: EVOTAZ is not recommended in patients with any Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or degree of hepatic impairment. (2.4, 8.7) www.fda.gov/medwatch. ----------------------DOSAGE FORMS AND STRENGTHS--------------------­ --------------------------------DRUG INTERACTIONS----------------------------- • Tablets: 300 mg of atazanavir and 150 mg of cobicistat. (3) Coadministration of EVOTAZ can alter the concentration of other drugs and other drugs may alter the concentration of EVOTAZ, which may result in ------------------------------CONTRAINDICATIONS------------------------------­ known or potentially significant drug interactions. The potential drug-drug • EVOTAZ is contraindicated in patients with previously demonstrated interactions must be considered prior to and during therapy. (4, 7, 12.3) hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product. (4) ------------------------USE IN SPECIFIC POPULATIONS----------------------­ • Coadministration with certain drugs for which altered plasma concentrations • Pregnancy: EVOTAZ is not recommended during pregnancy and should not are associated with serious and/or life-threatening events or loss of be initiated in pregnant individuals; use of an alternative regimen is therapeutic effect. (4) recommended. (2.5, 8.1) • Lactation: Breastfeeding is not recommended due to the potential for --------------------------WARNINGS AND PRECAUTIONS--------------------­ postnatal HIV transmission. (8.2) • Cardiac conduction abnormalities: PR interval prolongation may occur in • Pediatrics: EVOTAZ is not recommended for patients weighing less than 35 some patients. Consider ECG monitoring in patients with preexisting kg. (8.4) conduction system disease or when administered with other drugs that may prolong the PR interval. (5.1, 6, 7.3, 12.2, 17) See 17 for PATIENT COUNSELING INFORMATION and FDA- • Severe skin reactions: Discontinue if severe rash develops. (5.2, 6.1, 17) approved patient labeling. Revised: 07/2020 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 5 WARNINGS AND PRECAUTIONS 1.1 Indications 5.1 Cardiac Conduction Abnormalities 1.2 Limitations of Use 5.2 Severe Skin Reactions 2 DOSAGE AND ADMINISTRATION 5.3 Effects on Serum Creatinine 2.1 Laboratory Testing Prior to Initiation and During 5.4 New Onset or Worsening Renal Impairment When Treatment with EVOTAZ Used with Tenofovir DF 2.2 Recommended Dosage 5.5 Chronic Kidney Disease 2.3 Dosage in Patients with Renal Impairment 5.6 Nephrolithiasis and Cholelithiasis 2.4 Not Recommended in Patients with Any Degree 5.7 Hepatotoxicity of Hepatic Impairment 5.8 Risk of Serious Adverse Reactions or Loss of 2.5 Not Recommended During Pregnancy Virologic Response Due to Drug Interactions 3 DOSAGE FORMS AND STRENGTHS 5.9 Antiretrovirals that are Not Recommended 4 CONTRAINDICATIONS 5.10 Hyperbilirubinemia 1 Reference ID: 4649915 5.11 Immune Reconstitution Syndrome 11 DESCRIPTION 5.12 Diabetes Mellitus/Hyperglycemia 12 CLINICAL PHARMACOLOGY 5.13 Fat Redistribution 12.1 Mechanism of Action 5.14 Hemophilia 12.2 Pharmacodynamics 6 ADVERSE REACTIONS 12.3 Pharmacokinetics 6.1 Clinical Trial Experience 12.4 Microbiology 6.2 Postmarketing Experience 13 NONCLINICAL TOXICOLOGY 7 DRUG INTERACTIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of 7.1 Potential for EVOTAZ to Affect Other Drugs Fertility 7.2 Potential for Other Drugs to Affect EVOTAZ 14 CLINICAL STUDIES 7.3 Established and Other Potentially Significant Drug 14.1 Clinical Trial Results in Treatment-Naive Adult Interactions Subjects with HIV-1 Infection - Study GS-US-216­ 7.4 Drugs with No Observed or Predicted Interactions 0114 with the Components of EVOTAZ 14.2 Clinical Trial Results in HIV-1 Infected 8 USE IN SPECIFIC POPULATIONS Virologically Suppressed Pediatric Subjects ­ 8.1 Pregnancy Study GS-US-216-0128 8.2 Lactation 16 HOW SUPPLIED/STORAGE AND HANDLING 8.3 Females and Males of Reproductive Potential 17 PATIENT COUNSELING INFORMATION 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment * Sections or subsections omitted from the full prescribing information are 8.7 Hepatic Impairment not listed. 10 OVERDOSAGE 2 Reference ID: 4649915 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Indications EVOTAZ is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in the following populations [see Dosage and Administration (2.2, 2.3)]: • Adult patients • Pediatric patients weighing at least 35 kg. 1.2 Limitations of Use Use of EVOTAZ in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions [see Microbiology (12.4)]. 2 DOSAGE AND ADMINISTRATION 2.1 Laboratory Testing Prior to Initiation and During Treatment with EVOTAZ Renal Testing Renal laboratory testing should be performed in all patients prior to initiation of EVOTAZ and continued during treatment with EVOTAZ. Renal laboratory
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