----------------------- DOSAGE AND ADMINISTRATION -------------------------- HIGHLIGHTS OF PRESCRIBING INFORMATION • Before initiating TRIZIVIR, screen for the HLA-B*5701 allele because These highlights do not include all the information needed to use TRIZIVIR contains abacavir. (2.1) TRIZIVIR safely and effectively. See full prescribing information for • Adults and pediatric patients weighing at least 40 kg: 1 tablet twice daily. TRIZIVIR. (2.2) TRIZIVIR® (abacavir, lamivudine, and zidovudine) tablets, for oral use • Because TRIZIVIR is a fixed-dose tablet and cannot be dose adjusted, Initial U.S. Approval: 2000 TRIZIVIR is not recommended in patients requiring dosage adjustment or patients with hepatic impairment. (2.3, 4) WARNING: HYPERSENSITIVITY REACTIONS, HEMATOLOGIC TOXICITY, MYOPATHY, LACTIC ACIDOSIS AND SEVERE --------------------- DOSAGE FORMS AND STRENGTHS---------------------- HEPATOMEGALY WITH STEATOSIS, and EXACERBATIONS OF • Tablets: 300 mg abacavir, 150 mg lamivudine, and 300 mg zidovudine. HEPATITIS B (3) See full prescribing information for complete boxed warning. ------------------------------ CONTRAINDICATIONS ------------------------------- Hypersensitivity Reactions • Presence of HLA-B*5701 allele. (4) • Serious and sometimes fatal hypersensitivity reactions have occurred • Prior hypersensitivity reaction to abacavir, lamivudine, or zidovudine. (4) with abacavir-containing products. (5.1) • Moderate or severe hepatic impairment. (4, 8.7) • Hypersensitivity to abacavir is a multi-organ clinical syndrome. (5.1) • Patients who carry the HLA-B*5701 allele are at a higher risk of ----------------------- WARNINGS AND PRECAUTIONS ------------------------ experiencing a hypersensitivity reaction to abacavir. (5.1) • Hepatic decompensation, some fatal, has occurred in HIV-1/HCV • TRIZIVIR is contraindicated in patients with a prior hypersensitivity co-infected patients receiving combination antiretroviral therapy and reaction to abacavir and in HLA-B*5701-positive patients. (4) interferon alfa with or without ribavirin. Discontinue TRIZIVIR as • Discontinue TRIZIVIR as soon as a hypersensitivity reaction is medically appropriate and consider dose reduction or discontinuation of suspected. Regardless of HLA-B*5701 status, permanently discontinue interferon alfa, ribavirin, or both. (5.6) TRIZIVIR if hypersensitivity cannot be ruled out, even when other • Exacerbation of anemia has been reported in HIV-1/HCV co-infected diagnoses are possible. (5.1) patients receiving ribavirin and zidovudine. Coadministration of ribavirin • Following a hypersensitivity reaction to TRIZIVIR, NEVER restart and zidovudine is not advised. (5.6) TRIZIVIR or any other abacavir-containing product. (5.1) • Immune reconstitution syndrome and redistribution/accumulation of body Hematologic Toxicity fat have been reported in patients treated with combination antiretroviral • Hematologic toxicity, including neutropenia and anemia, has been therapy. (5.7, 5.8) associated with the use of zidovudine, a component of TRIZIVIR. (5.2) Myopathy ------------------------------ ADVERSE REACTIONS ------------------------------- The most commonly reported adverse reactions (incidence at least 10%) in • Symptomatic myopathy associated with prolonged use of zidovudine. clinical trials were nausea, headache, malaise and fatigue, and nausea and (5.3) vomiting. (6.1) Lactic Acidosis and Severe Hepatomegaly with Steatosis • Lactic acidosis and severe hepatomegaly with steatosis, including fatal To report SUSPECTED ADVERSE REACTIONS, contact ViiV cases, have been reported with the use of nucleoside analogues. (5.4) Healthcare at 1-877-844-8872 or FDA at 1-800-FDA-1088 or Exacerbations of Hepatitis B www.fda.gov/medwatch. • Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human ------------------------------ DRUG INTERACTIONS-------------------------------- immunodeficiency virus (HIV-1) and have discontinued lamivudine, a • Methadone: An increased methadone dose may be required in a small component of TRIZIVIR. Monitor hepatic function closely in these number of patients. (7.1) patients and, if appropriate, initiate anti-hepatitis B treatment. (5.5) • Agents antagonistic with zidovudine: Concomitant use should be avoided. (7.2) ------------------------------ RECENT MAJOR CHANGES ------------------------------ • Hematologic/bone marrow suppressive/cytotoxic agents: May increase Warnings and Precautions, Related Products that are Not Removed – the hematologic toxicity of zidovudine. (7.2) Recommended (5.11) 02/2017 ----------------------- USE IN SPECIFIC POPULATIONS ------------------------ ------------------------------ INDICATIONS AND USAGE ------------------------------- • Lactation: Women infected with HIV should be instructed not to TRIZIVIR, a combination of abacavir, lamivudine, and zidovudine, each breastfeed due to potential for HIV transmission. (8.2) nucleoside analogue HIV-1 reverse transcriptase inhibitors, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 See 17 for PATIENT COUNSELING INFORMATION and Medication infection. (1) Guide. Revised: 03/2017 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: HYPERSENSITIVITY REACTIONS, 5.5 Patients with Hepatitis B Virus Co-infection HEMATOLOGIC TOXICITY, MYOPATHY, LACTIC ACIDOSIS 5.6 Use with Interferon- and Ribavirin-Based Regimens AND SEVERE HEPATOMEGALY WITH STEATOSIS, AND 5.7 Immune Reconstitution Syndrome EXACERBATIONS OF HEPATITIS B 5.8 Fat Redistribution 1 INDICATIONS AND USAGE 5.9 Myocardial Infarction 2 DOSAGE AND ADMINISTRATION 5.10 Therapy-Experienced Patients 2.1 Screening for HLA-B*5701 Allele prior to Starting 6 ADVERSE REACTIONS TRIZIVIR 6.1 Clinical Trials Experience 2.2 Recommended Dosage for Adults and Pediatric Patients 6.2 Postmarketing Experience Weighing at Least 40 kg 7 DRUG INTERACTIONS 2.3 Not Recommended Due to Lack of Dosage Adjustment 7.1 Abacavir 3 DOSAGE FORMS AND STRENGTHS 7.2 Zidovudine 4 CONTRAINDICATIONS 8 USE IN SPECIFIC POPULATIONS 5 WARNINGS AND PRECAUTIONS 8.1 Pregnancy 5.1 Hypersensitivity Reactions 8.2 Lactation 5.2 Hematologic Toxicity/Bone Marrow Suppression 8.4 Pediatric Use 5.3 Myopathy 8.5 Geriatric Use 5.4 Lactic Acidosis and Severe Hepatomegaly with Steatosis 8.6 Patients with Impaired Renal Function 1 Reference ID: 4069722 8.7 Patients with Impaired Hepatic Function 13 NONCLINICAL TOXICOLOGY 10 OVERDOSAGE 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 11 DESCRIPTION 13.2 Animal Toxicology and/or Pharmacology 12 CLINICAL PHARMACOLOGY 14 CLINICAL STUDIES 12.1 Mechanism of Action 16 HOW SUPPLIED/STORAGE AND HANDLING 12.3 Pharmacokinetics 17 PATIENT COUNSELING INFORMATION 12.4 Microbiology *Sections or subsections omitted from the full prescribing information are not listed. FULL PRESCRIBING INFORMATION WARNING: HYPERSENSITIVITY REACTIONS, HEMATOLOGIC TOXICITY, MYOPATHY, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, and EXACERBATIONS OF HEPATITIS B Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir, a component of TRIZIVIR (abacavir, lamivudine, and zidovudine). Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele [see Warnings and Precautions (5.1)]. TRIZIVIR is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients [see Contraindications (4), Warnings and Precautions (5.1)]. All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with TRIZIVIR or reinitiation of therapy with TRIZIVIR, unless patients have a previously documented HLA-B*5701 allele assessment. Discontinue TRIZIVIR immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible [see Contraindications (4), Warnings and Precautions (5.1)]. Following a hypersensitivity reaction to TRIZIVIR, NEVER restart TRIZIVIR or any other abacavir-containing product because more severe symptoms, including death, can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity [see Warnings and Precautions (5.1)]. Hematologic Toxicity Zidovudine, a component of TRIZIVIR, has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced Human Immunodeficiency Virus (HIV-1) disease [see Warnings and Precautions (5.2)]. Myopathy Prolonged use of zidovudine has been associated with symptomatic myopathy [see Warnings and Precautions (5.3)]. Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue 2 Reference ID: 4069722 TRIZIVIR if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.4)]. Exacerbations of Hepatitis B Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine, a component of TRIZIVIR. Hepatic function should be monitored closely