IMPORTANT SAFETY INFORMATION  Prescribing Information, including Boxed WARNINGS and Medication Guide

EPZICOM contains abacavir, which is also contained in ZIAGEN® (abacavir sulfate) and TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine). Patients taking EPZICOM may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701 than if you do not.
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A randomized, double-blind trial to determine the clinical utility of HLA-B*5701 screening for abacavir hypersensitivity (ABC HSR)

• Background: Small studies have indicated a correlation between abacavir hypersensitivity and the presence of the HLA-B*5701 allele. This trial evaluated the effects of prospective screening for HLA-B*5701 on the rate of hypersensitivity.
• Methods: In this study, 1,956 abacavir-native patients with HIV-1 infection and unknown HLA-B*5701 status, most of whom were white, were randomized in a 1:1 ratio to receive either prospective or retrospective HLA-B*5701 determination. Prospectively screened patients who were HLA-B*5701 positive were removed from the study, and the remaining subjects in both arms received 6 weeks of abacavir-containing therapy. Skin patch testing was a research tool used in this study to determine if a patient with a clinical diagnosis of hypersensitivity also had an immune-mediated reaction to abacavir.
• Results: The rate of clinically suspected hypersensitivity was significantly less in the prospectively screened arm (3.4%) than in the control arm (7.8%) (P<0.0001). When coupled with skin patch testing, the rate of clinically suspected hypersensitivity with a positive skin patch test was 0 in the prospectively screened arm and 2.7% in the control arm (P<0.0001).
  
  
• Conclusions: Prospective HLA-B*5701 screening was effective in identifying patients who had a higher risk of hypersensitivity to abacavir, and screening out patients positive for HLA-B*5701 can reduce the overall incidence of HSR.

Important Points to Keep in Mind:

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 abacavir if hypersensitivity cannot be ruled out, even when other diagnoses are possible.

Results from HLA-B*5701 testing to assess risk for abacavir HSR should never substitute for appropriate clinical vigilance and patient management in individuals undergoing treatment with abacavir-containing products.

Results from pharmacogenetic testing, as with any laboratory test, should be evaluated as part of the overall clinical diagnosis and management of a patient.

• 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
• In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making
• 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
• 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
• EPZICOM Tablets are contraindicated in patients with hepatic impairment
• 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
• 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
• 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
• 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)
• In one study of therapy-naive 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%)

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