HIGHLIGHTS OF PRESCRIBING INFORMATION once every 3 months while taking DESCOVY, and upon diagnosis of These highlights do not include all the information needed to use any other sexually transmitted infections (STIs). (2.2) DESCOVY safely and effectively. See full prescribing information • Recommended dosage: for DESCOVY. • Treatment of HIV-1 Infection: One tablet taken once daily with or ® without food in patients with body weight at least 25 kg. (2.3) DESCOVY (emtricitabine and tenofovir alafenamide) tablets, for • HIV-1 PrEP: One tablet taken once daily with or without food in oral use individuals with body weight at least 35 kg. (2.4) Initial U.S. Approval: 2015 • Renal impairment: DESCOVY is not recommended in individuals with WARNING: POST-TREATMENT ACUTE EXACERBATION OF estimated creatinine clearance below 30 mL per minute. (2.5) HEPATITIS B and RISK OF DRUG RESISTANCE WITH USE ----------------------DOSAGE FORMS AND STRENGTHS--------------------­ OF DESCOVY FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS Tablets: 200 mg of FTC and 25 mg of TAF (3) (PrEP) IN UNDIAGNOSED EARLY HIV-1 INFECTION See full prescribing information for complete boxed warning. -------------------------------CONTRAINDICATIONS------------------------------­ DESCOVY for HIV-1 PrEP is contraindicated in individuals with Severe acute exacerbations of hepatitis B (HBV) have been unknown or positive HIV-1 status. (4) reported in HBV-infected individuals who have discontinued products containing emtricitabine (FTC) and/or tenofovir -----------------------WARNINGS AND PRECAUTIONS-----------------------­ disoproxil fumarate (TDF), and may occur with • Comprehensive management to reduce the risk of sexually discontinuation of DESCOVY. Hepatic function should be transmitted infections (STIs), including HIV-1, when DESCOVY is monitored closely in these individuals. If appropriate, used for HIV-1 PrEP: Counsel on adherence to daily dosing and safer anti-hepatitis B therapy may be warranted. (5.1) sex practices, including condoms, to reduce the risk of STIs. (5.2) • DESCOVY used for HIV-1 PrEP must only be prescribed to Management to reduce the risk of acquiring HIV-1 drug resistance individuals confirmed to be HIV-negative immediately prior to when DESCOVY is used for HIV-1 PrEP: refer to full prescribing initiating and at least every 3 months during use. information for additional detail. (5.2) Drug-resistant HIV-1 variants have been identified with use of • Immune reconstitution syndrome during treatment of HIV-1 infection: FTC/TDF for HIV-1 PrEP following undetected acute HIV-1 May necessitate further evaluation and treatment. (5.3) infection. Do not initiate DESCOVY for HIV-1 PrEP if signs or • New onset or worsening renal impairment: Assess serum creatinine, symptoms of acute HIV-1 infection are present unless estimated creatinine clearance, urine glucose, and urine protein when negative infection status is confirmed. (5.2) initiating DESCOVY and during use on a clinically appropriate schedule in all individuals. Also assess serum phosphorus in ----------------------------RECENT MAJOR CHANGES-------------------------­ individuals with chronic kidney disease. (5.4) Boxed Warning 10/2019 • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue Indications and Usage (1.2) 10/2019 DESCOVY in individuals who develop symptoms or laboratory Dosage and Administration (2.1, 2.2, 2.4, 2.5) 10/2019 findings suggestive of lactic acidosis or pronounced hepatotoxicity. Contraindications (4) 10/2019 (5.5) Warnings and Precautions (5.2) 10/2019 -------------------------------ADVERSE REACTIONS-----------------------------­ • In HIV-1 infected patients, the most common adverse reaction ----------------------------INDICATIONS AND USAGE---------------------------­ (incidence greater than or equal to 10%, all grades) was nausea. (6.1) HIV-1 Treatment (1.1): DESCOVY is a two-drug combination of emtricitabine (FTC) and • In HIV-1 uninfected adults in a PrEP trial, the most common adverse tenofovir alafenamide (TAF), both HIV nucleoside analog reverse reaction (incidence greater than or equal to 5%, all grades) was transcriptase inhibitors (NRTIs), and is indicated: diarrhea. (6.1) • in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least To report SUSPECTED ADVERSE REACTIONS, contact Gilead 35 kg. Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or • in combination with other antiretroviral agents other than protease www.fda.gov/medwatch. inhibitors that require a CYP3A inhibitor for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than -------------------------------DRUG INTERACTIONS------------------------------­ 35 kg. Consult the Full Prescribing Information prior to and during use for HIV-1 PrEP (1.2): potential drug interactions. (7, 12.3) DESCOVY is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of ------------------------USE IN SPECIFIC POPULATIONS----------------------­ HIV-1 infection from sexual acquisition, excluding individuals at risk from • Lactation: Mothers infected with HIV-1 should be instructed not to receptive vaginal sex. Individuals must have a negative HIV-1 test breastfeed, due to the potential for HIV transmission. (8.2) immediately prior to initiating DESCOVY for HIV-1 PrEP. • Pediatrics: Limitations of Use (1.2): • Treatment of HIV-1 Infection: Not recommended for patients The indication does not include use of DESCOVY in individuals at risk of weighing less than 25 kg. (8.4) HIV-1 from receptive vaginal sex because effectiveness in this • HIV-1 PrEP: Not recommended for individuals weighing less than population has not been evaluated. 35 kg. (8.4) ------------------------DOSAGE AND ADMINISTRATION---------------------­ See 17 for PATIENT COUNSELING INFORMATION and Medication • Testing: Prior to or when initiating DESCOVY, test for hepatitis B virus Guide. infection. Prior to or when initiating DESCOVY, and during use on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all Revised: 10/2019 individuals. In individuals with chronic kidney disease, also assess serum phosphorus. (2.1) • HIV-1 Screening: Screen all individuals for HIV-1 infection immediately prior to initiating DESCOVY for HIV-1 PrEP and at least Gilead Sciences 1 Reference ID: 4501324 FULL PRESCRIBING INFORMATION: CONTENTS* 7 DRUG INTERACTIONS WARNING: POST-TREATMENT ACUTE EXACERBATION OF 7.1 Potential for Other Drugs to Affect One or More Components of HEPATITIS B AND RISK OF DRUG RESISTANCE WITH USE OF DESCOVY DESCOVY FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN 7.2 Drugs Affecting Renal Function UNDIAGNOSED EARLY HIV-1 INFECTION 7.3 Established and Other Potentially Significant Interactions 1 INDICATIONS AND USAGE 7.4 Drugs without Clinically Significant Interactions with DESCOVY 1.1 Treatment of HIV-1 Infection 8 USE IN SPECIFIC POPULATIONS 1.2 HIV-1 Pre-Exposure Prophylaxis (PrEP) 8.1 Pregnancy 2 DOSAGE AND ADMINISTRATION 8.2 Lactation 2.1 Testing When Initiating and During Use of DESCOVY for 8.4 Pediatric Use Treatment of HIV-1 Infection or for HIV-1 PrEP 8.5 Geriatric Use 2.2 HIV-1 Screening for Individuals Receiving DESCOVY for HIV-1 8.6 Renal Impairment PrEP 8.7 Hepatic Impairment 2.3 Recommended Dosage for Treatment of HIV-1 Infection in 10 OVERDOSAGE Adults and Pediatric Patients Weighing at Least 25 kg 11 DESCRIPTION 2.4 Recommended Dosage for HIV-1 PrEP in Adults and 12 CLINICAL PHARMACOLOGY Adolescents Weighing at Least 35 kg 12.1 Mechanism of Action 2.5 Not Recommended in Individuals with Severe Renal Impairment 12.2 Pharmacodynamics for Treatment of HIV-1 Infection or for HIV-1 PrEP 12.3 Pharmacokinetics 3 DOSAGE FORMS AND STRENGTHS 12.4 Microbiology 4 CONTRAINDICATIONS 13 NONCLINICAL TOXICOLOGY 5 WARNINGS AND PRECAUTIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.1 Severe Acute Exacerbation of Hepatitis B in Individuals with 13.2 Animal Toxicology and/or Pharmacology HBV Infection 14 CLINICAL STUDIES 5.2 Comprehensive Management to Reduce the Risk of Sexually 14.1 Overview of Clinical Trials Transmitted Infections, Including HIV-1, and Development of 14.2 Clinical Trial Results for Treatment of HIV-1 HIV-1 Resistance When DESCOVY Is Used for HIV-1 PrEP 14.3 Clinical Trial Results for HIV-1 PrEP 5.3 Immune Reconstitution Syndrome 16 HOW SUPPLIED/STORAGE AND HANDLING 5.4 New Onset or Worsening Renal Impairment 17 PATIENT COUNSELING INFORMATION 5.5 Lactic Acidosis/Severe Hepatomegaly with Steatosis *Sections or subsections omitted from the full prescribing information 6 ADVERSE REACTIONS are not listed. 6.1 Clinical Trials Experience 6.2 Postmarketing Experience 2 Reference ID: 4501324 FULL PRESCRIBING INFORMATION WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B and RISK OF DRUG RESISTANCE WITH USE OF DESCOVY FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED EARLY HIV-1 INFECTION Severe acute exacerbations of hepatitis B (HBV) have been reported in HBV-infected individuals who have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of DESCOVY. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in individuals who are infected with HBV and discontinue DESCOVY. If appropriate, anti-hepatitis B therapy may be warranted