HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------------------ CONTRAINDICATIONS ----------------------------- These highlights do not include all the information needed to use • Previous hypersensitivity reaction to dolutegravir. (4) DOLUTEGRAVIR, EMTRICITABINE AND TENOFOVIR • Coadministration with dofetilide. (4) ALAFENAMIDE TABLETS safely and effectively. See full prescribing information for DOLUTEGRAVIR, EMTRICITABINE AND ----------------------- WARNINGS AND PRECAUTIONS ----------------------- TENOFOVIR ALAFENAMIDE TABLETS. • Hepatotoxicity has been reported in patients receiving a dolutegravir- containing regimen. Monitoring for hepatotoxicity is recommended. DOLUTEGRAVIR, EMTRICITABINE and TENOFOVIR (5.1) ALAFENAMIDE tablets, for oral use • Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been WARNING: POST TREATMENT ACUTE EXACERBATION OF reported. Discontinue dolutegravir, emtricitabine and tenofovir HEPATITIS B alafenamide tablets and other suspect agents immediately if signs or See full prescribing information for complete boxed warning. symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. (5.2) • Tenofovir alafenamide, one component of dolutegravir, • Immune reconstitution syndrome has been reported in patients treated emtricitabine and tenofovir alafenamide tablets, is approved for the with combination antiretroviral therapy. (5.5) treatment of chronic hepatitis B virus (HBV) infection. Severe acute • New onset or worsening renal impairment: Assess creatinine clearance, exacerbations of hepatitis B have been reported in patients who are urine glucose, and urine protein in all patients before initiating coinfected with HIV-1 and HBV and have discontinued products dolutegravir, emtricitabine and tenofovir alafenamide tablets therapy and containing tenofovir disoproxil fumarate (TDF), and may occur with monitor during therapy. Monitor serum phosphorus in patients with discontinuation of dolutegravir, emtricitabine and tenofovir chronic kidney disease. (5.6) alafenamide tablets. Hepatic function should be monitored closely in • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue these patients. If appropriate, initiation of anti-hepatitis B therapy treatment in patients who develop symptoms or laboratory findings may be warranted. (5.4) suggestive of lactic acidosis or pronounced hepatotoxicity. (5.7) --------------------------- INDICATIONS AND USAGE --------------------------- ------------------------------ ADVERSE REACTIONS ------------------------------ Dolutegravir, emtricitabine and tenofovir alafenamide is a three-drug Dolutegravir: The most common adverse reactions of moderate to severe combination of dolutegravir (integrase strand transfer inhibitor [INSTI]), intensity and incidence at least 2% (in those receiving dolutegravir in any one emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV nucleoside adult trial) are insomnia, fatigue, and headache. (6.1) analog reverse transcriptase inhibitors (NRTIs), and is indicated for use alone as a complete regimen for the treatment of HIV-1 infection in adults and Emtricitabine and Tenofovir Alafenamide: Most common adverse reaction pediatric patients weighing at least 40 kg. (1) (incidence greater than or equal to 10%, all grades) is nausea. (6.1) Limitations of Use: To report SUSPECTED ADVERSE REACTIONS, contact Mylan • Dolutegravir, emtricitabine and tenofovir alafenamide tablets alone are Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1- not recommended in patients with resistance-associated integrase 800-FDA-1088 or www.fda.gov/medwatch. substitutions or clinically suspected integrase strand transfer inhibitor resistance because the dose of dolutegravir in dolutegravir, emtricitabine ------------------------------ DRUG INTERACTIONS ------------------------------ and tenofovir alafenamide tablets is insufficient in these subpopulations. Coadministration of dolutegravir, emtricitabine and tenofovir alafenamide See the dolutegravir prescribing information. (1) tablets with other drugs can alter the concentration of other drugs and other • Dolutegravir, emtricitabine, and tenofovir alafenamide tablets are not drugs may alter the concentrations of dolutegravir, emtricitabine and tenofovir indicated for use as pre-exposure prophylaxis (PrEP) to reduce the risk alafenamide tablets. The potential drug-drug interactions must be considered of sexually acquired HIV-1 in adults at high risk. prior to and during therapy. (4, 7, 12.3) ---------------------- DOSAGE AND ADMINISTRATION ----------------------- ---------------------- USE IN SPECIFIC POPULATIONS ----------------------- • Testing: Prior to initiation of dolutegravir, emtricitabine and tenofovir • Pregnancy: Dolutegravir, emtricitabine and tenofovir alafenamide tablets alafenamide tablets, patients should be tested for hepatitis B virus should be used during pregnancy only if the potential benefit justifies the infection, and estimated creatinine clearance, urine glucose, and urine potential risk. (8.1) protein should be obtained. (2.1) • Lactation: Breastfeeding is not recommended due to the potential for • Adults and pediatric patients weighing at least 40 kg: One tablet daily. HIV transmission. (8.2) May be taken with or without food. (2.2) • Pediatrics: Not recommended for patients weighing less than 40 kg. • Renal Impairment: Dolutegravir, emtricitabine and tenofovir (8.4) alafenamide tablets are not recommended in patients with estimated creatinine clearance below 30 mL per minute. (2.3) See 17 for PATIENT COUNSELING INFORMATION and FDA- approved patient labeling. ---------------------DOSAGE FORMS AND STRENGTHS ---------------------- Revised: 2/2018 Tablets: 50 mg of dolutegravir, 200 mg of FTC, and 25 mg of TAF (3) FULL PRESCRIBING INFORMATION: CONTENTS* 5.2 Hypersensitivity Reactions FULL PRESCRIBING INFORMATION 5.3 Risk of Adverse Reactions or Loss of Virologic WARNING: POST TREATMENT ACUTE EXACERBATION OF Response Due to Drug Interactions HEPATITIS B 5.4 Severe Acute Exacerbation of Hepatitis B in Patients 1 INDICATIONS AND USAGE Coinfected with HIV-1 and HBV 2 DOSAGE AND ADMINISTRATION 5.5 Immune Reconstitution Syndrome 2.1 Testing Prior to Initiation of Dolutegravir, 5.6 New Onset or Worsening Renal Impairment Emtricitabine and Tenofovir Alafenamide Tablets 5.7 Lactic Acidosis and Severe Hepatomegaly with 2.2 Adults and Pediatric Patients Weighing at Least 40 kg Steatosis (88 lbs) 6 ADVERSE REACTIONS 2.3 Not Recommended in Patients with Severe Renal 6.1 Clinical Trials Experience Impairment 6.2 Postmarketing Experience 3 DOSAGE FORMS AND STRENGTHS 7 DRUG INTERACTIONS 4 CONTRAINDICATIONS 7.1 Effect of Dolutegravir on the Pharmacokinetics of 5 WARNINGS AND PRECAUTIONS Other Agents 5.1 Hepatotoxicity Reference ID: 4219844 7.2 Effect of Other Agents on the Pharmacokinetics of 12.1 Mechanism of Action Dolutegravir or Emtricitabine and Tenofovir 12.2 Pharmacodynamics Alafenamide 12.3 Pharmacokinetics 7.3 Established and Other Potentially Significant Drug 12.4 Microbiology Interactions 13 NONCLINICAL TOXICOLOGY 7.4 Drugs Affecting Renal Function 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 8 USE IN SPECIFIC POPULATIONS 13.2 Animal Toxicology and/or Pharmacology 8.1 Pregnancy 14 CLINICAL STUDIES 8.2 Lactation 14.1 Adult Subjects 8.4 Pediatric Use 14.2 Pediatric Subjects 8.5 Geriatric Use 16 HOW SUPPLIED/STORAGE AND HANDLING 8.6 Hepatic Impairment 17 PATIENT COUNSELING INFORMATION 8.7 Renal Impairment 10 OVERDOSAGE *Sections or subsections omitted from the full prescribing information are not 11 DESCRIPTION listed. 12 CLINICAL PHARMACOLOGY 2 Reference ID: 4219844 FULL PRESCRIBING INFORMATION WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B • Tenofovir alafenamide, one component of dolutegravir, emtricitabine and tenofovir alafenamide tablets, is approved for the treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of dolutegravir, emtricitabine and tenofovir alafenamide tablets. 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 dolutegravir, emtricitabine and tenofovir alafenamide tablets. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.4)]. 1 INDICATIONS AND USAGE Dolutegravir, emtricitabine and tenofovir alafenamide tablets are indicated for use alone as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 40 kg. Limitations of Use: • Dolutegravir, emtricitabine and tenofovir alafenamide tablets alone are not recommended in patients with resistance-associated integrase substitutions or clinically suspected integrase strand transfer inhibitor resistance because the dose of dolutegravir in dolutegravir, emtricitabine and tenofovir alafenamide tablets is insufficient in these subpopulations. See the dolutegravir prescribing information. • Dolutegravir, emtricitabine and tenofovir alafenamide tablets are not indicated for use as pre- exposure prophylaxis (PrEP) to reduce the risk of sexually