HIGHLIGHTS OF PRESCRIBING INFORMATION Creatinine Clearance (mL/min) These highlights do not include all the information needed to use <15 mL/min EMTRIVA safely and effectively. See full prescribing information ≥50 30–49 15–29 Formulation or on for EMTRIVA. mL/min mL/min mL/min hemodialy ® EMTRIVA (emtricitabine) capsule, for oral use sisa ® EMTRIVA (emtricitabine) oral solution 200 mg Capsule 200 mg every 200 mg every 200 mg every every 96 Initial U.S. Approval: 2003 (200 mg) 24 hours 48 hours 72 hours hours WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH 60 mg STEATOSIS and POST TREATMENT EXACERBATION OF 240 mg every 120 mg every 80 mg every Oral Solution every HEPATITIS B 24 hours 24 hours 24 hours (10 mg/mL) 24 hours (24 mL) (12 mL) (8 mL) See full prescribing information for complete boxed warning. (6 mL) • Lactic acidosis and severe hepatomegaly with steatosis, a. Hemodialysis Patients: If dosing on day of dialysis, give dose including fatal cases, have been reported with the use of after dialysis. nucleoside analogs. (5.1) -----------------------DOSAGE FORMS AND STRENGTHS-------------------- • Emtriva is not approved for the treatment of chronic Hepatitis • Capsules: 200 mg (3) B virus (HBV) infection. Severe acute exacerbations of Hepatitis B have been reported in patients who have • Oral solution: 10 mg per mL (3) discontinued EMTRIVA. Hepatic function should be monitored closely in patients coinfected with HIV-1 and HBV. --------------------------------CONTRAINDICATIONS----------------------------- If appropriate, initiation of anti-Hepatitis B therapy may be EMTRIVA is contraindicated in patients with previously demonstrated warranted. (5.2) hypersensitivity to any of the components of the products. (4) ---------------------------RECENT MAJOR CHANGES--------------------------- ----------------------------WARNINGS AND PRECAUTIONS------------------- Indications and Usage (1) 11/2012 Warnings and Precautions • Products with same active ingredient: Do not use with other Coadministration with Other Products (5.3) 11/2012 emtricitabine-containing products (e.g., ATRIPLA, COMPLERA, Immune Reconstitution Syndrome (5.6) 11/2011 STRIBILD, and TRUVADA). (5.3) • Redistribution/accumulation of body fat: Observed in patients ---------------------------INDICATIONS AND USAGE----------------------------- receiving antiretroviral therapy. (5.5) EMTRIVA, a nucleoside analog HIV-1 reverse transcriptase inhibitor, is • Immune reconstitution syndrome: May necessitate further indicated in combination with other antiretroviral agents for the evaluation and treatment. (5.6) treatment of HIV-1 infection. (1) -------------------------------ADVERSE REACTIONS------------------------------ -------------------------DOSAGE AND ADMINISTRATION---------------------- Most common adverse reactions (incidence ≥10%) are headache, • EMTRIVA may be taken without regard to food. (2.1) diarrhea, nausea, fatigue, dizziness, depression, insomnia, abnormal • Adult Patients (18 years of age and older) (2.2): dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis. Skin hyperpigmentation was very common (≥10%) in pediatric patients. • EMTRIVA capsules: one 200 mg capsule administered once (6) daily orally. To report SUSPECTED ADVERSE REACTIONS, contact Gilead • EMTRIVA oral solution: 240 mg (24 mL) administered once Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or daily orally. www.fda.gov/medwatch. • Pediatric Patients (0–3 months of age) (2.3): ---------------------------USE IN SPECIFIC POPULATIONS-------------------- • EMTRIVA oral solution: 3 mg/kg administered once daily • Nursing mothers: Women infected with HIV should be instructed orally. not to breast feed. (8.3) • Pediatric Patients (3 months through 17 years) (2.4): • Pediatrics: Dose adjustment based on age and weight. (2.3, 2.4, 12.3) • EMTRIVA oral solution: 6 mg/kg up to a maximum of 240 mg (24 mL) administered once daily orally. See 17 for PATIENT COUNSELING INFORMATION and FDA- approved patient labeling. • EMTRIVA capsules: for children weighing more than 33 kg who can swallow an intact capsule, one 200 mg capsule administered once daily orally. Revised: November 2012 • Dose interval adjustment in adult patients with renal impairment (2.5): Gilead Sciences 1 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS B 1 INDICATIONS AND USAGE 10 OVERDOSAGE 2 DOSAGE AND ADMINISTRATION 11 DESCRIPTION 2.1 Recommended Dose 12 CLINICAL PHARMACOLOGY 2.2 Adult Patients (18 years of age and older) 12.1 Mechanism of Action 2.3 Pediatric Patients (0–3 months of age) 12.3 Pharmacokinetics 2.4 Pediatric Patients (3 months through 17 years) 12.4 Microbiology 2.5 Dose Adjustment in Adult Patients with Renal 13 NONCLINICAL TOXICOLOGY Impairment 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 3 DOSAGE FORMS AND STRENGTHS 14 CLINICAL STUDIES 4 CONTRAINDICATIONS 14.1 Treatment-Naive Adult Patients 5 WARNINGS AND PRECAUTIONS 14.2 Treatment-Experienced Adult Patients 5.1 Lactic Acidosis/Severe Hepatomegaly with Steatosis 14.3 Pediatric Patients 5.2 Patients Coinfected with HIV-1 and HBV 16 HOW SUPPLIED/STORAGE AND HANDLING 5.3 Coadministration with Related Products 17 PATIENT COUNSELING INFORMATION 5.4 New Onset or Worsening Renal Impairment 17.1 Information for Patients 5.5 Fat Redistribution 5.6 Immune Reconstitution Syndrome 6 ADVERSE REACTIONS *Sections or subsections omitted from the full prescribing information 6.1 Adverse Reactions from Clinical Trials Experience are not listed 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Patients with Impaired Renal Function Gilead Sciences 2 FULL PRESCRIBING INFORMATION WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS B Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals [See Warnings and Precautions (5.1)]. EMTRIVA is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of EMTRIVA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA. 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 EMTRIVA. If appropriate, initiation of anti-hepatitis B therapy may be warranted [See Warnings and Precautions (5.2)]. 1 INDICATIONS AND USAGE EMTRIVA® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Additional important information regarding the use of EMTRIVA for the treatment of HIV-1 Infection: • EMTRIVA should not be coadministered with ATRIPLA®, COMPLERA®, STRIBILD™, TRUVADA®, or lamivudine-containing products [See Warnings and Precautions (5.3)]. • In treatment-experienced patients, the use of EMTRIVA should be guided by laboratory testing and treatment history [See Clinical Pharmacology (12.4)]. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dose EMTRIVA may be taken without regard to food. 2.2 Adult Patients (18 years of age and older) • EMTRIVA capsules: one 200 mg capsule administered once daily orally. • EMTRIVA oral solution: 240 mg (24 mL) administered once daily orally. 2.3 Pediatric Patients (0–3 months of age) • EMTRIVA oral solution: 3 mg per kg administered once daily orally. 2.4 Pediatric Patients (3 months through 17 years) • EMTRIVA oral solution: 6 mg per kg up to a maximum of 240 mg (24 mL) administered once daily orally. Gilead Sciences 3 • EMTRIVA capsules: for children weighing more than 33 kg who can swallow an intact capsule, one 200 mg capsule administered once daily orally. 2.5 Dose Adjustment in Adult Patients with Renal Impairment Significantly increased drug exposures were seen when EMTRIVA was administered to subjects with renal impairment [See Clinical Pharmacology (12.3)]. Therefore, the dosing interval or dose of EMTRIVA should be adjusted in patients with baseline creatinine clearance less than 50 mL per min using the following guidelines (see Table 1). The safety and effectiveness of these dose adjustment guidelines have not been clinically evaluated. Therefore, clinical response to treatment and renal function should be closely monitored in these patients. Table 1 Dose Adjustment in Adult Patients with Renal Impairment Creatinine Clearance (mL/min) <15 mL/min Formulation ≥50 mL/min 30–49 mL/min 15–29 mL/min or on hemodialysisa 200 mg Capsule 200 mg every 200 mg every 200 mg every every (200 mg) 24 hours 48 hours 72 hours 96 hours 240 mg every 120 mg every 80 mg every 60 mg every Oral Solution 24 hours 24 hours 24 hours 24 hours (10 mg/mL) (24 mL) (12 mL) (8 mL) (6 mL) a. Hemodialysis Patients: If dosing on day of dialysis, give dose after dialysis. Although there are insufficient data to recommend a specific dose adjustment of EMTRIVA in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval similar to adjustments for adults should be considered. 3 DOSAGE FORMS AND STRENGTHS EMTRIVA is available as capsules and oral solution. EMTRIVA capsules, containing 200 mg of emtricitabine, are size 1 hard gelatin capsules with a blue cap and white body, printed with “200 mg” in