EPZICOM, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.

The pharmacokinetics of abacavir and lamivudine have not been studied in subjects over 65 years of age.

In pediatric patients weighing less than 25 kg, use of abacavir and lamivudine as single products is recommended to achieve appropriate dosing.

Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of EPZICOM. These hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment. Patients who carry the HLA-B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA-B*5701 allele have developed hypersensitivity reactions.

EPZICOM is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients. All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with EPZICOM or reinitiation of therapy with EPZICOM, unless patients have a previously documented HLA B*5701 allele assessment. Discontinue EPZICOM immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible.

Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in subjects dually infected with HIV-1 and HBV. Emergence of hepatitis B virus variants associated with resistance to lamivudine has been reported in HIV-1-infected subjects who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus.

Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine, which is a 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 co-infected with HIV-1 and HB

EPZICOM is contraindicated in patients:

• who have the HLA-B*5701 allele
• with prior hypersensitivity reaction to abacavir or lamivudine
• with moderate or severe hepatic impairment

Following a hypersensitivity reaction to EPZICOM, NEVER restart EPZICOM 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.

EPZICOM is not recommended for:

• patients with creatinine clearance less than 50 mL per minute
• patients with mild hepatic impairment

The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment; therefore, EPZICOM is contraindicated in these patients.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPZICOM if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

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.

Several prospective, observational, epidemiological studies have reported an association with the use of abacavir and the risk of myocardial infarction (MI).As a precaution, 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 (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).

Administration of EPZICOM with other products containing abacavir or lamivudine is not recommended. In addition, do not administer EPZICOM in combination with products containing emtricitabine. 

In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased.

Co-administration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines.

Co-administration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions.The riociguat dose may need to be reduced.

Ethanol decreases the elimination of abacavir causing an increase in overall exposure.

Ribavirin reduces phosphorylation of lamivudine, stavudine, and zidovudine.

Abacavir has been shown to cross the placenta and concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery. Lamivudine crosses the placenta in humans. 

The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1.

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• Use in patients under 3 months of age. GoToSource

⚠️  Patients with the HLA-B*5701 allele gene are at a higher risk of abacavir hypersensitivity reactions.

Myocardial infarction. GoToSource

Life-threatening hypersensitivity reaction with multiorgan involvement, stroke, congestive heart failure, peripheral vascular disease, anemia, dyslipidemia, lipoatrophy and lactic acidosis. GoToSource

Liver injury. GoToSource

Hyperlipidaemia (high level of fat in the blood), hypertriglyceridemia (elevated triglyceride levels), increased blood bilirubin and rash. GoToSource

Ototoxicity (damage to the ear). GoToSource 

Increased limb-fat mass. GoToSource

Stevens-johnson syndrome (severe skin reaction). GoToSource

Loss of bone mineral density. GoToSource

No major injury lawsuits reported.