Rx Care

New antiretroviral for AIDS combines efficacy, simplicity

Combination products make treatment regimens for HIV/AIDS easier to follow, because such regimens often require the simultaneous use of three or more drugs from different classes. The Food & Drug Administration recently approved abacavir/lamivudine (Epzicom, GlaxoSmithKline) 600 mg/300 mg tablets for the treatment of HIV infection. The drug will be available in U.S. pharmacies by the end of August or in early September. The agency also approved another fixed-dose combination antiretroviral, tenofovir/emtricitabine (Truvada, Gilead Sciences) 300 mg/200 mg tablets, at the same time.

Epzicom may help those who have compliance issues, said Jeff Julian, Pharm.D., pharmacy manager for StatScript pharmacy in Kansas City, Mo. When the dosing schedule and adverse-effect profile are compatible with the patient's lifestyle, adherence is improved, he said.

No new or additive adverse effects are associated with this combination product, said Julian. He mentioned the findings of the CNA30021 study, which indicated comparable efficacy between 300 mg of abacavir (Ziagen, GlaxoSmithKline) dosed twice daily and 600 mg of abacavir dosed once daily, when given in combination with lamivudine (Epivir, GlaxoSmithKline) and efavirenz (Sustiva, Bristol-Myers Squibb).

The product labeling for abacavir/ lamivudine contains a boldfaced warning about the risk of hypersensitivity reactions, lactic acidosis and severe hepatomegaly, and exacerbations of hepatitis B. The manufacturer said that treatment with abacavir should be discontinued immediately if a hypersensitivity reaction is suspected. The company also advised clinicians not to reinitiate therapy with abacavir or any abacavir-containing product following a hypersensitivity reaction, because fatal rechallenge reactions have been associated with readministration of the drug.

Julian said that pharmacists will distribute a medication guide and laminated warning card summarizing the symptoms of an abacavir hypersensitivity reaction with each prescription and refill. The manufacturer has established an Abacavir Hypersensitivity Registry to facilitate the reporting of hypersensitivity reactions and collection of information about each case. Physicians can register patients by calling (800) 270-0425.

The recommended dose of abacavir/lamivudine is one tablet, taken daily in combination with other antiretroviral agents. Abacavir/lamivudine is not recommended for use with other nucleoside/nucleotide reverse transcriptase inhibitors. It is recommended for use with nonnucleoside reverse transcriptase inhibitors and protease inhibitors.

According to the company, abacavir/lamivudine is contraindicated for use in those with a creatinine clearance rate of less than 50 mL/ min. The product is also contraindicated in those with hepatic impairment. The manufacturer reported that the pharmacokinetics of abacavir/lamivudine in pediatric patients is under investigation. Insufficient data exist to recommend a dose at this time, however, so abacavir/lamivudine is contraindicated for use in children.

Julian recommended that pharmacists explain to patients that this new product actually contains two drugs, making their old medications unnecessary. He said pharmacists should also make patients aware that adherence to a medication taken once daily is particularly important, because missing a dose means missing a whole day of therapy, leaving patients vulnerable to resistance. If patients miss a dose of medication that is dosed twice daily, he explained, at least they are not missing a whole day of treatment.

The availability of a nucleoside backbone as a combination product will likely improve patient compliance, which represents the major "Achilles' heel" in the treatment of HIV infection, said Marshall Kubota, M.D., a clinical professor at the University of California at San Francisco. Findings of studies done over the past several years that enrolled thousands of patients attest to the efficacy of the abacavir/lamivudine combination, he continued. The two-in-one tablet represents a highly simplified therapy with a history of proven efficacy as part of an antiretroviral regimen, he concluded.

Charlotte LoBuono

TIPS TO REMEMBER: Epzicom

• Epzicom can be taken with or without food.

• Epzicom is classified as Pregnancy Category C. It should be used during pregnancy only if the benefits to the mother outweigh the potential risks to the fetus. The Centers for Disease Control & Prevention recommends that HIV-infected mothers not breast-feed their infants while taking Epzicom, as it is not yet known whether the drug passes into breast milk.

• The use of Epzicom in combination with zalcitabine (HIVID, Roche) is not recommended.

Charlotte LoBuono. New antiretroviral for AIDS combines efficacy, simplicity.

Drug Topics

Aug. 23, 2004;148:26.