Drug Information

Abacavir and lamivudine

Special Alerts

Abacavir: Update on the Risk of Myocardial Infarction March 2011

In July 2008, the U.S. Food and Drug Administration (FDA) notified healthcare professionals of a possible increased risk of myocardial infarction (MI) in patients taking nucleoside reverse transcriptase inhibitors (NRTIs), including abacavir, based on observational study data. Subsequently, the FDA completed a meta-analysis of 26 abacavir randomized clinical trials conducted between 1996 and 2010. Although several observational studies and one randomized controlled trial showed an increased risk of MI, the FDA has concluded there is not an increased risk of MI with abacavir use based on the overall meta-analysis.

For additional information, please refer to file://www.fda.gov/Drugs/DrugSafety/ucm245164.htm.

ALERT: U.S. Boxed WarningThe FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Brand Names: U.S.

  • Epzicom®
Brand Names: Canada

  • Kivexa™
Medication GuideAn FDA-approved patient medication guide, which is available with the product information and at file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088592.pdf, must be dispensed with this medication. A Warning Card (summarizing symptoms of hypersensitivity), which is available with the product information, must also be dispensed with this medication for each new outpatient prescription and refill.
Pharmacologic Category

  • Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
Dosing: AdultHIV: Oral: One tablet (abacavir 600 mg and lamivudine 300 mg) once daily
Dosing: Renal ImpairmentClcr <50 mL/minute: Use not recommended
Dosing: Hepatic ImpairmentUse contraindicated.
Dosage Forms: U.S.Excipient information presented when available (limited, particularly for generics); consult specific product labeling.Tablet:

Epzicom®: Abacavir 600 mg and lamivudine 300 mg

Generic Equivalent Available: U.S.No
AdministrationMay be administered with or without food.
UseTreatment of HIV infections in combination with other antiretroviral agents
Adverse Reactions SignificantSee individual agents.Postmarketing and/or case reports: Alopecia, anaphylaxis, anemia, aplastic anemia, breath sounds abnormal, CPK increased, erythema multiforme, fat redistribution, hepatic steatosis, hepatitis B exacerbation, hyperglycemia, hypersensitivity reaction, lactic acidosis, lymphadenopathy, muscle weakness, pancreatitis, paresthesia, peripheral neuropathy, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, urticaria, weakness, wheezing

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ContraindicationsHypersensitivity to abacavir, lamivudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status.
Warnings/Precautions Boxed warnings:• Chronic hepatitis B: See “Disease-related concerns” below.

• HIV: Appropriate use: See “Disease-related concerns” below.

• Hypersensitivity reactions: See “Concerns related to adverse effects” below.

• Lactic acidosis/hepatomegaly: See “Concerns related to adverse effects” below.

Concerns related to adverse effects:

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Epzicom®). Patients testing positive for the presence of the HLA-B*5701 allele are at an increased risk for hypersensitivity reactions. Screening for HLA-B*5701 allele status is recommended prior to initiating abacavir-containing therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated abacavir therapy. Epzicom® is not recommended in patients testing positive for the HLA-B*5701 allele . Additionally, HLA-B*5701 allele-positive patients (including abacavir treatment naïve) should have an allergy to abacavir documented in the patient’s medical record (DHHS, 2011). Reactions usually occur within 9 days of starting abacavir; ~90% occur within 6 weeks. Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Epzicom® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Epzicom® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Epzicom® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. To report these events on Epzicom® hypersensitivity, a registry has been established (1-800-270-0425).

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• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required.

• Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).

Disease-related concerns:

• Coronary heart disease: Use has been associated with an increased risk of myocardial infarction (MI) in observational studies; however, based on a meta-analysis of 26 randomized trials, the FDA has concluded there is not an increased risk. Consider using with caution in patients with risks for coronary heart disease and minimizing modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking) prior to use.

• Chronic hepatitis B: [U.S. Boxed Warning]: Following discontinuation of lamivudine, severe acute exacerbations of hepatitis B in patients coinfected with HBV and HIV have been reported. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. Lamivudine-resistant HBV variants have been reported in coinfected patients using lamivudine as part of an antiretroviral regimen.

• HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated.

• Renal impairment: Due to fixed dose of combination product, use is not recommended with renal impairment (Clcr <50 mL/minute).

Concurrent drug therapy issues:

• Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.

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Special populations:

• Pediatrics: Due to fixed dose of combination product, use is not recommended in children.

Drug Interactions

(For additional information

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination

Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification

Protease Inhibitors: May decrease the serum concentration of Abacavir. Risk C: Monitor therapy

Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification

Trimethoprim: May decrease the excretion of LamiVUDine. Risk C: Monitor therapy

Ethanol/Nutrition/Herb InteractionsEthanol: Ethanol may increase the risk of toxicity.
Pregnancy Risk FactorC
Pregnancy ImplicationsSee individual agents.
LactationSee individual agents.
Breast-Feeding ConsiderationsSee individual agents.
Dietary ConsiderationsMay be taken with or without food.
Pricing: U.S. (www.drugstore.com)Tablets (Epzicom)600-300 mg (30): $977.61

Monitoring ParametersAmylase, bilirubin, blood glucose, serum creatine kinase, liver enzymes, hematologic parameters, triglycerides, viral load, and CD4 count; HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status; signs and symptoms of hypersensitivity, particularly in patients untested for the HLA-B*5701 allele
International Brand Names

  • Kivexa (AR, AT, AU, BE, BG, CH, CN, CO, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PT, RU, SE, SG, TH, TR, TW, UY)
Mechanism of ActionNucleoside reverse transcriptase inhibitor combination.Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.

Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.