lamivudine/abacavir (Rx)

Contraindications

Patients who have the HLA-B*5701 allele

Prior hypersensitivity to abacavir or lamivudine

Moderate or severe hepatic impairment

Cautions

Review medical history for hypersensitivity to abacavir before administration; discontinue at first signs of hypersensitivity

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogues, including abacavir and lamivudine (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 develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity

Exacerbation of hepatitis B may occur on discontinuation

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

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

Concomitant administration of emtricitabine with lamivudine-containing products not recommended

Hepatic decompensation, some fatal, reported in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy and interferon alfa with or without ribavirin; discontinue therapy as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both

Pregnancy

If pregnant woman exposed to abacavir, report to the Antiretroviral Pregnancy Registry 1-800-258-4263

Available data from antiretroviral pregnancy registry show no difference in overall risk of birth defects for abacavir or lamivudine compared with background rate for birth defects of 2.7% in Metropolitan Atlanta Congenital Defects Program (MACDP) reference population

Lactation

Abacavir and lamivudine are present in human milk; there is no information on effects of abacavir and lamivudine 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, instruct mothers not to breastfeed if they are receiving therapy

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

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