INDICATION AND USAGE

• EPZICOM, in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection. EPZICOM is one of multiple products containing abacavir
• Before starting EPZICOM, review medical history for prior exposure to any abacavir-containing product in order to avoid reintroduction in a patient with a history of hypersensitivity to abacavir
• In one controlled study, more patients taking abacavir 600 mg once daily had severe hypersensitivity reactions compared to patients taking abacavir 300 mg twice daily
• As a part of a triple-drug regimen, EPZICOM is recommended for use with ART agents from different pharmacological classes and not with other NRTIs

IMPORTANT SAFETY INFORMATION

Hypersensitivity Reactions

• EPZICOM contains abacavir sulfate, which has been associated with serious and sometimes fatal hypersensitivity reactions. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: (1) fever, (2) rash, (3) gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain), (4) constitutional (including generalized malaise, fatigue, or achiness), and (5) respiratory (including dyspnea, cough, or pharyngitis). Discontinue EPZICOM as soon as a hypersensitivity reaction is suspected
• Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended; this approach has been found to decrease the risk of hypersensitivity reaction
• Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir
• HLA-B*5701—negative patients may develop a suspected hypersensitivity reaction to abacavir; however, this occurs significantly less frequently than in HLA-B*5701—positive patients
• Regardless of HLA-B*5701 status, permanently discontinue EPZICOM if hypersensitivity cannot be ruled out, even when other diagnoses are possible
• Following a hypersensitivity reaction to abacavir, NEVER restart EPZICOM or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death
• Reintroduction of EPZICOM or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours

• Hypersensitivity to abacavir was reported in approximately 8% of 2,670 patients (n=206) in 9 clinical trials (range 2% to 9%) with enrollment from November 1999 to February 2002

Lactic Acidosis

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, lamivudine, and other antiretrovirals

Coinfection with Hepatitis B or HCV

• Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV and have discontinued lamivudine, which is one component of EPZICOM. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue EPZICOM and are coinfected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted
• Hepatic decompensation (some fatal) has occurred in HIV/HCV coinfected patients receiving combination antiretroviral therapy for HIV and interferon with or without ribavirin. Patients receiving interferon with or without ribavirin and EPZICOM should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of EPZICOM should be considered as medically appropriate

Impaired Hepatic Function

• EPZICOM Tablets are contraindicated in patients with hepatic impairment

Immune Reconstitution Syndrome

• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EPZICOM. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment
• Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment

Fat Redistribution

• Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown

Cardiovascular

• An observational study showed an increase in MI with abacavir; a sponsor-conducted, pooled analysis did not show increased risk. In totality, the available data are inconclusive
• The underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking)

Impaired Renal Function

• Since EPZICOM is a fixed-dose tablet and the lamivudine component cannot be dose-adjusted, EPZICOM is not recommended for patients with creatinine-clearance <50 mL/min

Use With Other Abacavir-, Lamivudine- and/or Emtricitabine-Containing Products

• Do not use EPZICOM with other abacavir-, lamivudine- and/or emtricitabine-containing products

Adverse Events

• In one study of therapy-naïve patients (CNA30021), the most common adverse events (grade 2-4) reported with abacavir and lamivudine dosed once daily were hypersensitivity (9%), insomnia (7%), depression (7%), headache/migraine (7%), fatigue (6%), dizziness (6%), nausea (5%), diarrhea (5%), rash (5%), pyrexia (5%), abdominal pain (4%), abnormal dreams (4%), and anxiety (3%)