HIGHLIGHTS OF PRESCRIBING INFORMATION • Hepatic impairment: BIKTARVY is not recommended in patients These highlights do not include all the information needed to use with severe hepatic impairment. (2.4) BIKTARVY safely and effectively. See full prescribing information for BIKTARVY. ----------------------DOSAGE FORMS AND STRENGTHS--------------------­ Tablets: 50 mg of bictegravir (equivalent to 52.5 mg of bictegravir BIKTARVY® (bictegravir, emtricitabine, and tenofovir alafenamide) sodium), 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide tablets, for oral use (equivalent to 28 mg of tenofovir alafenamide fumarate). (3) Initial U.S. Approval: 2018 -------------------------------CONTRAINDICATIONS------------------------------­ WARNING: POST TREATMENT ACUTE EXACERBATION OF BIKTARVY is contraindicated to be co-administered with: HEPATITIS B • dofetilide. (4) See full prescribing information for complete boxed warning. • rifampin. (4) • Severe acute exacerbations of hepatitis B have been -----------------------WARNINGS AND PRECAUTIONS-----------------------­ reported in patients who are coinfected with HIV-1 and • Immune reconstitution syndrome: May necessitate further evaluation HBV and have discontinued products containing and treatment. (5.3) emtricitabine (FTC) and/or tenofovir disoproxil fumarate • New onset or worsening renal impairment: Assess serum creatinine, (TDF), and may occur with discontinuation of BIKTARVY. estimated creatinine clearance, urine glucose and urine protein Closely monitor hepatic function in these patients. If when initiating BIKTARVY and during therapy as clinically appropriate, anti-hepatitis B therapy may be warranted. appropriate in all patients. Also assess serum phosphorus in (5.1) patients with chronic kidney disease. (5.4) • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue ----------------------------RECENT MAJOR CHANGES-------------------------­ treatment in patients who develop symptoms or laboratory findings Indications and Usage (1) 06/2019 suggestive of lactic acidosis or pronounced hepatotoxicity. (5.5) Dosage and Administration, Recommended Dosage (2.2) 06/2019 Warnings and Precautions, Immune Reconstitution Syndrome (5.3) -------------------------------ADVERSE REACTIONS-----------------------------­ 06/2019 Most common adverse reactions (incidence greater than or equal to 5%, all grades) are diarrhea, nausea, and headache. (6.1) ----------------------------INDICATIONS AND USAGE---------------------------­ BIKTARVY is a three-drug combination of bictegravir (BIC), a human To report SUSPECTED ADVERSE REACTIONS, contact Gilead immunodeficiency virus type 1 (HIV-1) integrase strand transfer Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or inhibitor (INSTI), and emtricitabine (FTC) and tenofovir alafenamide www.fda.gov/medwatch. (TAF), both HIV-1 nucleoside analog reverse transcriptase inhibitors (NRTIs), and is indicated as a complete regimen for the treatment of -------------------------------DRUG INTERACTIONS------------------------------­ HIV-1 infection in adults and pediatric patients weighing at least 25 kg • Because BIKTARVY is a complete regimen, coadministration with who have no antiretroviral treatment history or to replace the current other antiretroviral medications for the treatment of HIV-1 infection is antiretroviral regimen in those who are virologically suppressed (HIV-1 not recommended. (7.1) RNA less than 50 copies per mL) on a stable antiretroviral regimen • with no history of treatment failure and no known substitutions Consult the Full Prescribing Information prior to and during associated with resistance to the individual components of BIKTARVY. treatment for important drug interactions. (4, 5.2, 7, 12.3) (1) ------------------------USE IN SPECIFIC POPULATIONS----------------------­ • ------------------------DOSAGE AND ADMINISTRATION----------------------­ Lactation: Women infected with HIV should be instructed not to • Testing: Prior to or when initiating BIKTARVY test for hepatitis B breastfeed due to the potential for HIV transmission. (8.2) virus infection. Prior to or when initiating BIKTARVY, and during • Pediatrics: Not recommended for patients weighing less than 25 kg. treatment, assess serum creatinine, estimated creatinine clearance, (8.4) urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, also assess See 17 for PATIENT COUNSELING INFORMATION and serum phosphorus. (2.1) FDA-approved patient labeling. • Recommended dosage: One tablet taken once daily with or without food in patients weighing at least 25 kg. (2.2) Revised: 08/2019 • Renal impairment: BIKTARVY is not recommended in patients with estimated creatinine clearance below 30 mL per minute. (2.3) Gilead Sciences 1 Reference ID: 4472017 FULL PRESCRIBING INFORMATION: CONTENTS* 8 USE IN SPECIFIC POPULATIONS WARNING: POST TREATMENT ACUTE EXACERBATION OF 8.1 Pregnancy HEPATITIS B 8.2 Lactation 1 INDICATIONS AND USAGE 8.4 Pediatric Use 2 DOSAGE AND ADMINISTRATION 8.5 Geriatric Use 2.1 Testing When Initiating and During Treatment with BIKTARVY 8.6 Renal Impairment 2.2 Recommended Dosage 8.7 Hepatic Impairment 2.3 Not Recommended in Patients with Severe Renal Impairment 10 OVERDOSAGE 2.4 Not Recommended in Patients with Severe Hepatic Impairment 11 DESCRIPTION 3 DOSAGE FORMS AND STRENGTHS 12 CLINICAL PHARMACOLOGY 4 CONTRAINDICATIONS 12.1 Mechanism of Action 5 WARNINGS AND PRECAUTIONS 12.2 Pharmacodynamics 5.1 Severe Acute Exacerbation of Hepatitis B in Patients 12.3 Pharmacokinetics Coinfected with HIV-1 and HBV 12.4 Microbiology 5.2 Risk of Adverse Reactions or Loss of Virologic Response Due 13 NONCLINICAL TOXICOLOGY to Drug Interactions 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.3 Immune Reconstitution Syndrome 13.2 Animal Toxicology and/or Pharmacology 5.4 New Onset or Worsening Renal Impairment 14 CLINICAL STUDIES 5.5 Lactic Acidosis/Severe Hepatomegaly with Steatosis 14.1 Description of Clinical Trials 6 ADVERSE REACTIONS 14.2 Clinical Trial Results in HIV-1 Subjects with No Antiretroviral 6.1 Clinical Trials Experience Treatment History 6.2 Postmarketing Experience 14.3 Clinical Trial Results in HIV-1 Virologically-Suppressed 7 DRUG INTERACTIONS Subjects Who Switched to BIKTARVY 7.1 Other Antiretroviral Medications 14.4 Clinical Trial Results in HIV-1 Infected Pediatric Subjects 7.2 Potential for BIKTARVY to Affect Other Drugs Between the Ages of 6 to Less than 18 Years 7.3 Potential Effect of Other Drugs on One or More Components of 16 HOW SUPPLIED/STORAGE AND HANDLING BIKTARVY 17 PATIENT COUNSELING INFORMATION 7.4 Drugs Affecting Renal Function *Sections or subsections omitted from the full prescribing information 7.5 Established and Potentially Significant Drug Interactions are not listed. 7.6 Drugs without Clinically Significant Interactions with BIKTARVY Gilead Sciences 2 Reference ID: 4472017 FULL PRESCRIBING INFORMATION WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)]. 1 INDICATIONS AND USAGE BIKTARVY is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 25 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of BIKTARVY. 2 DOSAGE AND ADMINISTRATION 2.1 Testing When Initiating and During Treatment with BIKTARVY Prior to or when initiating BIKTARVY, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1)]. Prior to or when initiating BIKTARVY, and during treatment with BIKTARVY, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, also assess serum phosphorus [see Warnings and Precautions (5.4)]. 2.2 Recommended Dosage BIKTARVY is a three-drug fixed dose combination product containing 50 mg of bictegravir (BIC), 200 mg of emtricitabine (FTC), and 25 mg of tenofovir alafenamide (TAF). The recommended dosage of BIKTARVY is one tablet taken orally once daily with or without food in adults and pediatric patients weighing at least 25 kg [see Clinical Pharmacology (12.3)]. 3 Reference ID: 4472017 2.3 Not Recommended in Patients with Severe Renal Impairment BIKTARVY is not recommended in patients with estimated creatinine clearance below 30 mL per minute [see Use in Specific Populations (8.6)]. 2.4 Not Recommended in Patients with Severe Hepatic Impairment BIKTARVY is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. 3 DOSAGE FORMS AND STRENGTHS Each BIKTARVY tablet contains 50 mg of bictegravir (BIC) (equivalent