lamivudine/zidovudine/abacavir (Rx)

>10%

Nausea

Headache

Fatigue

Malaise

Vomiting

1-10%

Rash

Fever/chills

Anxiety

Depression

Increased triglyceride levels

Diarrhea

Increased amylase

Neutropenia

Increased ALT

Increased CPK

Ear infection

Nose/throat infection

Viral infection

Frequency Not Defined

Immune reconstitution syndrome

GGT increased

Fat redistribution

Pancreatitis

Contraindications

Hypersensitivity to any component

Moderate or severe hepatic impairment

Presence of HLA-B*5701 allele

Cautions

Immune reconstitution syndrome reported with combination ART; during the initial treatment phase, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis); autoimmune disorders (eg, Grave disease, polymyositis, and Guillain-Barré syndrome) have also been reported

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with use of nucleoside analogues, including abacavir, lamivudine, and zidovudine (components of the combination product); a majority of these cases have been in women; female gender and obesity may be risk factors; suspend dosing in those who develop clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity

Use has been associated with increased risk of myocardial infarction in observational studies, but not in a meta-analysis of 26 randomized trials; caution with risks for coronary heart disease and minimizing modifiable risk factors, including smoking, hypertension, and hyperlipidemia, prior to use

Use caution when treating in combination with interferon alfa with or without ribavirin in HIV/HBV; monitor for hepatic decompensation, neutropenia, or anemia and reduce interferon dose and or ribavirin or discontinue if toxicity occurs

Discontinue therapy as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both in co-infected patients receiving combination antiretroviral therapy and interferon alfa with or without ribavirin

Exacerbation of anemia reported in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine; coadministration of ribavirin and zidovudine not advised

Treatment with zidovudine, a component of the combination formulation, has been associated with loss of subcutaneous fat; the incidence and severity of lipoatrophy are related to cumulative exposure; this fat loss, which is most evident in the face, limbs, and buttocks, may be only partially reversible and improvement may take months to years after switching to a non-zidovudine-containing regimen; patients should be regularly assessed for signs of lipoatrophy during therapy with zidovudine-containing products, and if feasible, therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy

Not for administration with other products containing abacavir, lamivudine, or zidovudine; or emtricitabine-containing products

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to the drug during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

Abacavir

• Based on prospective reports to APR of exposures to abacavir during pregnancy resulting in live births (including over 1,300 exposed in the first trimester and over 1,300 exposed in the second/third trimester), there was no difference between overall risk of birth defects for abacavir compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP
• The prevalence of defects in live births was 3.2% (95% CI: 2.3% to 4.3%) following first-trimester exposure to abacavir-containing regimens and 2.9% (95% CI: 2.1% to 4.0%) following second/third-trimester exposure to abacavir-containing regimens

Lamivudine

• Based on prospective reports to APR of exposures to lamivudine during pregnancy resulting in live births (including over 5,300 exposed in first trimester and over 7,400 exposed in second/third trimester), there was no difference between overall risk of birth defects for lamivudine compared with background birth defect rate of 2.7% in U.S. reference population of MACDP
• The prevalence of birth defects in live births was 3.1% (95% CI: 2.7% to 3.6%) following first-trimester exposure to lamivudine-containing regimens and 2.9% (95% CI: 2.5%, 3.3%) following second/third-trimester exposure to lamivudine- containing regimens

Zidovudine

• Based on prospective reports to the APR of exposures during pregnancy resulting in live births (including over 4,200 exposed in the first trimester and over 9,700 exposed in the second/third trimester), there was no difference between the overall risk of birth defects for zidovudine compared with the background birth defect rate of 2.7% in a U.S. reference population of the MACDP

Lactation

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 infection; abacavir, lamivudine and zidovudine are present in human milk; there is no information on effects of abacavir, lamivudine and zidovudine on breastfed infant or effects of drug on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in breastfed infant, similar to those seen in adults; instruct mothers not to breastfeed if they are being treated with the drug combination

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Pharmacogenomics

Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction

Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended

For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended

Genetic testing laboratories

• The following companies provide genetic testing for HLA variants
• Kashi Clinical Laboratories (www.kashilab.com)
• LabCorp (http://www.labcorp.com/)
• Specialty Laboratories (http://www.specialtylabs.com)
• Quest (http://www.questdialgnotics.com)

Mechanism of Action

Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog

Zidovudine: NRTI; interferes with HIV viral RNA-dependent DNA polymerase (inhibits viral replication); thymidine analog

Abacavir: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by inhibiting viral replication; guanosine analogue