HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------------------CONTRAINDICATIONS------------------------------- These highlights do not include all the information needed to use Coadministration of GENVOYA is contraindicated with drugs that: GENVOYA safely and effectively. See full prescribing information • Are highly dependent on CYP3A for clearance and for which for GENVOYA. elevated plasma concentrations are associated with serious adverse events. (4) GENVOYA® (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) tablets, for oral use • Strongly induce CYP3A, which may lead to lower exposure of one or Initial U.S. Approval: 2015 more components and loss of efficacy of GENVOYA and possible resistance. (4) WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B -----------------------WARNINGS AND PRECAUTIONS------------------------ See full prescribing information for complete boxed warning. • Risk of adverse reactions or loss of virologic response due to drug interactions: The concomitant use of GENVOYA and other drugs Severe acute exacerbations of hepatitis B have been may result in known or potentially significant drug interactions, some reported in patients who are coinfected with HIV-1 and HBV of which may lead to loss of therapeutic effect of GENVOYA and and have discontinued products containing emtricitabine possible development of resistance; clinically significant adverse and/or tenofovir disoproxil fumarate (TDF), and may occur reactions from greater exposures of concomitant drugs; or loss of with discontinuation of GENVOYA. Hepatic function should therapeutic effect of concomitant drugs. (5.2) be monitored closely in these patients. If appropriate, anti- • Immune reconstitution syndrome: May necessitate further evaluation hepatitis B therapy may be warranted. (5.1) and treatment. (5.3) • New onset or worsening renal impairment: Assess serum creatinine, ---------------------------RECENT MAJOR CHANGES--------------------------- estimated creatinine clearance, urine glucose and urine protein Warnings and Precautions, Risk of Adverse Reactions or when initiating GENVOYA and during therapy on a clinically Loss of Virologic Response Due to Drug Interactions (5.2) 12/2020 appropriate schedule in all patients. Also assess serum phosphorus Warnings and Precautions, Immune Reconstitution in patients with chronic kidney disease. (5.4) Syndrome (5.3) 12/2020 • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue Warnings and Precautions, New Onset or Worsening Renal treatment in patients who develop symptoms or laboratory findings Impairment (5.4) 03/2021 suggestive of lactic acidosis or pronounced hepatotoxicity. (5.5) ----------------------------INDICATIONS AND USAGE---------------------------- -------------------------------ADVERSE REACTIONS------------------------------ GENVOYA is a four-drug combination of elvitegravir, an HIV-1 Most common adverse reaction (incidence greater than or equal to integrase strand transfer inhibitor (INSTI), cobicistat, a CYP3A 10%, all grades) is nausea. (6.1) inhibitor, and emtricitabine and tenofovir alafenamide (TAF), both HIV- 1 nucleoside analog reverse transcriptase inhibitors (NRTIs), and To report SUSPECTED ADVERSE REACTIONS, contact Gilead is indicated as a complete regimen for the treatment of HIV-1 infection Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or in adults and pediatric patients weighing at least 25 kg who have no www.fda.gov/medwatch. antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less -------------------------------DRUG INTERACTIONS------------------------------- than 50 copies per mL) on a stable antiretroviral regimen for at least 6 GENVOYA should not be administered with other antiretroviral months with no history of treatment failure and no known substitutions • medications for treatment of HIV-1 infection. (7.1) associated with resistance to the individual components of GENVOYA. (1) • GENVOYA can alter the concentration of drugs metabolized by CYP3A or CYP2D6. Drugs that induce CYP3A can alter the ------------------------DOSAGE AND ADMINISTRATION----------------------- concentrations of one or more components of GENVOYA. Consult • Testing: Prior to or when initiating GENVOYA test for hepatitis B the full prescribing information prior to and during treatment for virus infection. Prior to or when initiating GENVOYA, and during potential drug-drug interactions. (4, 7.2, 7.3, 12.3) treatment on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine ------------------------USE IN SPECIFIC POPULATIONS----------------------- protein in all patients. In patients with chronic kidney disease, also • Pregnancy: Not recommended for use during pregnancy because of assess serum phosphorus. (2.1) substantially lower exposures of cobicistat and elvitegravir during • Recommended dosage: One tablet taken orally once daily with food pregnancy. GENVOYA should not be initiated in pregnant in patients with body weight at least 25 kg and a creatinine individuals. (2.5, 8.1) clearance greater than or equal to 30 mL per minute, or in adult • Lactation: Breastfeeding is not recommended due to the potential patients with creatinine clearance less than 15 mL per minute who for HIV transmission. (8.2) are receiving chronic hemodialysis. On days of hemodialysis, • Pediatrics: Not recommended for patients weighing less than 25 kg. administer GENVOYA after hemodialysis. (2.2) (8.4) • Renal impairment: GENVOYA is not recommended in patients with estimated creatinine clearance of 15 to below 30 mL per minute, or See 17 for PATIENT COUNSELING INFORMATION and below 15 mL per minute who are not receiving chronic hemodialysis. FDA-approved patient labeling. (2.3) • Hepatic impairment: GENVOYA is not recommended in patients Revised: 09/2021 with severe hepatic impairment. (2.4) ----------------------DOSAGE FORMS AND STRENGTHS--------------------- Tablets: 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide. (3) Gilead Sciences 1 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 GENVOYA 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 2.5 Not Recommended During Pregnancy 12 CLINICAL PHARMACOLOGY 3 DOSAGE FORMS AND STRENGTHS 12.1 Mechanism of Action 4 CONTRAINDICATIONS 12.2 Pharmacodynamics 5 WARNINGS AND PRECAUTIONS 12.3 Pharmacokinetics 5.1 Severe Acute Exacerbation of Hepatitis B in Patients Coinfected 12.4 Microbiology with HIV-1 and HBV 13 NONCLINICAL TOXICOLOGY 5.2 Risk of Adverse Reactions or Loss of Virologic Response Due to 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Drug Interactions 5.3 Immune Reconstitution Syndrome 13.2 Animal Toxicology and/or Pharmacology 14 CLINICAL STUDIES 5.4 New Onset or Worsening Renal Impairment 14.1 Description of Clinical Trials 5.5 Lactic Acidosis/Severe Hepatomegaly with Steatosis 6 ADVERSE REACTIONS 14.2 Clinical Trial Results in HIV-1 Treatment-Naïve Subjects 14.3 Clinical Trial Results in HIV-1 Virologically-Suppressed 6.1 Clinical Trials Experience Subjects Who Switched to GENVOYA 6.2 Postmarketing Experience 7 DRUG INTERACTIONS 14.4 Clinical Trial Results in HIV-1 Infected Subjects with Renal Impairment 7.1 Not Recommended with Other Antiretroviral Medications 14.5 Clinical Trial Results in HIV-1 Infected Pediatric Subjects 7.2 Potential for GENVOYA to Affect Other Drugs 7.3 Potential for Other Drugs to Affect One or More Components of Between the Ages of 6 to Less than 18 GENVOYA 16 HOW SUPPLIED/STORAGE AND HANDLING 7.4 Drugs Affecting Renal Function 17 PATIENT COUNSELING INFORMATION 7.5 Established and Other Potentially Significant Interactions 7.6 Drugs without Clinically Significant Interactions with GENVOYA * Sections or subsections omitted from the full prescribing information are not listed. Gilead Sciences 2 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 and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of GENVOYA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue GENVOYA. If appropriate, anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)]. 1 INDICATIONS AND USAGE GENVOYA is indicated as a complete regimen for the treatment of 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 for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of GENVOYA [see Clinical Studies (14)].