Pharmacology Update

Abacavir Sulfate and Lamivudine Tablets (Epzicom)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved a combination of 2 antiretrovirals, abacavir and lamivudine, for the treatment of HIV-1 infections. Each tablet contains 600 mg of abacavir and 300 mg of lamivudine for once daily administration. The combination is marketed by GlaxoSmithKline as Epzicom.

Indications

Abacavir/lamivudine is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infections.

Dosage

The recommended dose is one tablet daily. It may be taken without regard to meals.1

Abacavir/lamivudine is supplied at bottles of 30 tablets. Each containing 600 mg of abacavir and 300 mg of lamivudine.

Potential Advantages

The combination permits a once-daily dose of these 2 nucleoside reverse transcriptase inhibitors (NRTI) as one tablet thus reducing tablet burden and potentially improving compliance. The alternative would be 2 ´ 150 mg lamivudine and 2 ´ 300 mg of abacavir.

Potential Disadvantages

Missed doses of a once-daily regimen potentially has greater therapeutic consequence that with a multiple dose regimen. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir. In clinical trials, hypersensitivity was reported in about 8% of subjects with a median onset of 9 days.1

Comments

The combination of abacavir and lamivudine improves convenience and significantly reduces tablet burden when this 2-NRTI combination is used. The efficacy as a once daily regimen was assessed in a randomized, double-blind study in 770 HIV-infected, treatment naïve patients.1

Patients received either abacavir 600 mg daily or 300 mg twice daily with lamivudine 300 mg daily or efavirenz 600 mg twice daily. Through 48 weeks, no differences were detected between these regimens in terms of viral load or discontinuation due to adverse events or other reasons. Bioequivalence was established between abacavir/lamivudine as a single tablet and components administered individually.1 A regimen of abacavir, lamivudine, and efavirenz has been reported to be more effective than abacavir, lamivudine, and zidovudine.2 Similarly the combination of abacavir, lamivudine, and efavirenz was superior to that of abacavir, lamivudine, and tenofovir.3 The cost for abacavir/lamivudine is same as the sum of the components taken individually.

Clinical Implications

The preferred combination regimens for treatment naïve patients recommended by the Panel of Clinical Practices for Treatment of HIV-1 Infected Adults and Adolescents are efavirenz plus (zidovudine or tenofovir or stavudine) plus lamivudine.3 An alternative is efavirenz plus (either didanosine or abacavir) plus lamivudine. For two-NRTIs as part of a combination regimen, the Panel recommends lamivudine plus zidovudine or stavudine as combinations of choice. Abacavir and lamivudine may be used as alternatives. Epzicom offer a more convenient and lower tablet burden than the individual components when this combination is used.

Dr. Elliott, MD, FACP, is Chair of the Formulatory Committee at Northern California Kaiser Permanente and Assistant Clinical Professor of Medicine at the University of California, San Francisco. Dr. Chan, PharmD, PhD, is Pharmacy Quality and Outcomes Manager for Kaiser Permanente, Oakland, CA.

References

1. Epzicom Product Information. GlaxoSmithKline. August 2004.

2. Gulick RM, et al. N Engl J Med. 2004;350:1850-1861.

3. Panel on Clinical Practices for Treatment of HIV Infections. March 23, 2004 at http://aidsinfo.nih.gov/guidelines/adult/AA_032304.pdf.