HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use DOLUTEGRAVIR, EMTRICITABINE and TENOFOVIR -----------------------WARNINGS AND PRECAUTIONS------------------------ ALAFENAMIDE TABLETS safely and effectively. See full prescribing • Hypersensitivity reactions characterized by rash, constitutional findings, information for DOLUTEGRAVIR, EMTRICITABINE and and sometimes organ dysfunction, including liver injury have been TENOFOVIR ALAFENAMIDE TABLETS. reported. Discontinue dolutegravir, emtricitabine and tenofovir alafenamide tablets and other suspect agents immediately if signs or DOLUTEGRAVIR, EMTRICITABINE and TENOFOVIR symptoms of hypersensitivity reactions develop. (5.2) ALAFENAMIDE tablets, for oral use • Hepatotoxicity has been reported in patients receiving a dolutegravir- containing regimen. Monitoring for hepatotoxicity is recommended. WARNING: POST-TREATMENT ACUTE EXACERBATION OF (5.3) HEPATITIS B • Embryo-fetal toxicity may occur when used at the time of conception and in early pregnancy. An alternative treatment to dolutegravir, See full prescribing information for complete boxed warning. emtricitabine and tenofovir alafenamide tablets should be considered at the time of conception through the first trimester of pregnancy due to the Severe acute exacerbations of hepatitis B virus (HBV) have been reported risk of neural tube defects. Counsel adolescents and adults of in HBV-infected patients who have discontinued products containing childbearing potential to use effective contraception. (2.1, 5.4, 8.1, 8.3) emtricitabine and/or tenofovir disoproxil fumarate (TDF), and may occur • Immune reconstitution syndrome has been reported in patients treated with discontinuation of dolutegravir, emtricitabine and tenofovir with combination antiretroviral therapy. (5.6) alafenamide tablets. Hepatic function should be monitored closely in • New Onset or Worsening Renal Impairment. Assess serum creatinine, these patients. If appropriate, initiation of anti-hepatitis B therapy may estimated creatinine clearance, urine glucose, and urine protein when be warranted. (5.1) initiating dolutegravir, emtricitabine and tenofovir alafenamide tablets and during use on a clinically appropriate schedule in all patients. Also ----------------------------INDICATIONS AND USAGE--------------------------- assess serum phosphorus in patients with chronic kidney disease. (5.7) Dolutegravir, emtricitabine and tenofovir alafenamide tablets, a three-drug • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue combination of dolutegravir (integrase strand transfer inhibitor [INSTI]), treatment in patients who develop symptoms or laboratory findings emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV nucleoside suggestive of lactic acidosis or pronounced hepatotoxicity. (5.8) analog reverse transcriptase inhibitors (NRTIs), is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients -------------------------------ADVERSE REACTIONS------------------------------ weighing at least 25 kg. (1) • Dolutegravir: The most common adverse reactions of moderate to severe Limitations of Use: intensity and incidence at least 2% (in those receiving dolutegravir in any one adult trial) are insomnia, fatigue, headache and diarrhea. (6.1) • Dolutegravir, emtricitabine and tenofovir alafenamide tablets alone is not • Emtricitabine and Tenofovir Alafenamide: Most common adverse recommended in patients with resistance-associated integrase reaction (incidence greater than or equal to 10% all grades) is nausea. substitutions or clinically suspected integrase strand transfer inhibitor (6.1) resistance because the dose of dolutegravir in dolutegravir, emtricitabine and tenofovir alafenamide tablets is insufficient in these subpopulations. To report SUSPECTED ADVERSE REACTIONS, contact Laurus See the dolutegravir prescribing information. (1) Generics Inc. at 1-833-3-LAURUS (1-833-352-8787) or FDA at 1-800- • Dolutegravir, emtricitabine and tenofovir alafenamide tablets is not FDA-1088 or www.fda.gov/medwatch. indicated for use as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk. -------------------------------DRUG INTERACTIONS------------------------------ Coadministration of dolutegravir, emtricitabine and tenofovir alafenamide ------------------------DOSAGE AND ADMINISTRATION---------------------- tablets with other drugs can alter the concentration of other drugs and other • Pregnancy Testing: Perform pregnancy testing before initiation of drugs may alter the concentration of dolutegravir, emtricitabine and tenofovir dolutegravir, emtricitabine and tenofovir alafenamide tablets in alafenamide tablets. The potential drug-drug interactions must be considered adolescents and adults of childbearing potential. (2.1, 5.4) prior to and during therapy. (4, 7, 12.3) • Testing: Prior to or when initiating dolutegravir, emtricitabine and tenofovir alafenamide tablets, test for hepatitis B virus infection. Prior to ------------------------USE IN SPECIFIC POPULATIONS----------------------- • or when initiating dolutegravir, emtricitabine and tenofovir alafenamide Pregnancy: An alternative treatment to dolutegravir, emtricitabine and tablets, and during treatment, assess serum creatinine, estimated tenofovir alafenamide tablets should be considered at the time of creatinine clearance, urine glucose, and urine protein in all patients as conception through the first trimester due to the risk of neural tube clinically appropriate. In patients with chronic kidney disease, also defects. (2.1, 5.4, 8.1) assess serum phosphorus. (2.1) • Lactation: Breastfeeding is not recommended due to the potential for • Recommended dosage: One tablet taken once daily in adults and HIV transmission. (8.2) pediatric patients weighing at least 25 kg. May be taken with or without • Females and males of reproductive potential: Pregnancy testing and food. (2.2) contraception are recommended in adolescents and adults of • Renal impairment: Dolutegravir, emtricitabine and tenofovir childbearing potential. (8.3) alafenamide tablets is not recommended in patients with estimated • Pediatrics: Not recommended for patients weighing less than 25 kg. creatinine clearance below 30 mL per minute. (2.3) (8.4) • Hepatic impairment: Dolutegravir, emtricitabine and tenofovir ----------------------DOSAGE FORMS AND STRENGTHS--------------------- alafenamide tablets is not recommended in patients with severe hepatic Tablets: 50 mg of dolutegravir, 200 mg of emtricitabine and 25 mg of impairment (Child-Pugh Score C). (8.7) tenofovir alafenamide (3) See 17 for PATIENT COUNSELING INFORMATION and FDA- -------------------------------CONTRAINDICATIONS------------------------------ approved patient labeling. • Previous hypersensitivity reaction to dolutegravir. (4) Issued: 12/2020 • Coadministration with dofetilide. (4) _______________________________________________________________________________________________________________________________________ Page 1 of 43 Reference ID: 4711890 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: POST-TREATMENT ACUTE EXACERBATION Dolutegravir, FTC, or TAF OF HEPATITIS B 7.3 Established and Other Potentially Significant Drug Interactions 1 INDICATIONS AND USAGE 7.4 Drugs without Clinically Significant Interactions with Dolutegravir, FTC, and TAF 2 DOSAGE AND ADMINISTRATION 7.5 Drugs Affecting Renal Function 2.1 Testing Prior to Initiation and During Treatment with Dolutegravir, Emtricitabine and Tenofovir Alafenamide 8 USE IN SPECIFIC POPULATIONS Tablets 8.1 Pregnancy 2.2 Recommended Dosage in Adults and Pediatric Patients 8.2 Lactation Weighing at Least 25 kg (55 lbs) 8.3 Females and Males of Reproductive Potential 2.3 Not Recommended in Patients with Severe Renal 8.4 Pediatric Use Impairment 8.5 Geriatric Use 2.4 Not Recommended in Patients with Severe Hepatic 8.6 Renal Impairment Impairment 8.7 Hepatic Impairment 3 DOSAGE FORMS AND STRENGTHS 10 OVERDOSAGE 4 CONTRAINDICATIONS 11 DESCRIPTION 5 WARNINGS AND PRECAUTIONS 12 CLINICAL PHARMACOLOGY 5.1 Severe Acute Exacerbation of Hepatitis B in Patients with 12.1 Mechanism of Action HBV Infection 12.2 Pharmacodynamics 5.2 Hypersensitivity Reactions 12.3 Pharmacokinetics 5.3 Hepatotoxicity 12.4 Microbiology 5.4 Embryo-Fetal Toxicity 5.5 Risk of Adverse Reactions or Loss of Virologic Response 13 NONCLINICAL TOXICOLOGY Due to Drug Interactions 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.6 Immune Reconstitution Syndrome 13.2 Animal Toxicology and/or Pharmacology 5.7 New Onset or Worsening Renal Impairment 5.8 Lactic Acidosis and Severe Hepatomegaly with Steatosis 14 CLINICAL STUDIES 14.1 Adult Subjects 6 ADVERSE REACTIONS 14.2 Pediatric Subjects 6.1 Clinical Trials Experience 6.2 Postmarketing Experience 16 HOW SUPPLIED/STORAGE AND HANDLING 7 DRUG INTERACTIONS 17 PATIENT COUNSELING INFORMATION 7.1 Effect of Dolutegravir on the Pharmacokinetics of Other Agents *Sections or subsections omitted from the full prescribing 7.2 Effect of Other Agents on the Pharmacokinetics of information are not listed. Page 2 of 43 Reference ID: 4711890 FULL PRESCRIBING INFORMATION WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients who have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of dolutegravir, emtricitabine