July 23, 2008

Allergy Testing, Heart Risk Assessment Recommended Before Starting Abacavir

All HIV-positive people considering an antiretroviral regimen that contains abacavir—the active component in Ziagen and also found in Epzicom and Trizivir—should first be tested for a human gene that has been closely tied to a serious allergic reaction to the drug, according to new language added to Ziagen’s official prescribing information. The prescribing information, or label, was also amended to include information about a possible increased risk of heart attacks in patients using abacavir, and to stress that underlying risk factors for cardiovascular disease—such as smoking, high blood pressure, diabetes and high cholesterol and triglyceride levels—be considered and minimized when considering the drug.

Various studies have shown that HIV-positive people with an inherited gene called HLA-B*5701 are significantly more likely to experience a severe allergy to abacavir than those who don’t have the gene. This allergy, frequently referred to as an abacavir hypersensitivity reaction (AHR), is a serious side effect that occurs in about 5 percent of those taking the drug. Symptoms, including fever, rash and shortness of breath, often worsen with continued use of the drug and can be fatal, especially if abacavir is stopped and then restarted.

The label now recommends HLA-B*5701 screening—a simple, cheap and widely available blood test—for any patient before initiating HIV treatment with abacavir, or before restarting it in patients who have previously tolerated abacavir but whose HLA-B*5701 status is unknown. Research confirms that the screening significantly decreases the risk of AHR because patients who test positive for the gene can avoid abacavir.

The added cardiovascular language is based on the 30,000-patient Data collection of Adverse effects on anti-HIV Drugs (D:A:D) study, which suggested that current or recent use of abacavir may be associated with an increased risk of a heart attack. However, the revised label also includes an analysis of 54 clinical trials sponsored by GlaxoSmithKline (GSK), the manufacturer of abacavir, which failed to find a relationship between abacavir use and an increased risk of heart attacks. “In totality,” the U.S. Food and Drug Administration-approved label states, “the available data from [D:A:D] and [the 54] clinical trials are inconclusive.”

As a precaution, GSK requested an update to the label to suggest that health care providers consider the underlying risk of coronary heart disease when prescribing medications containing abacavir and to urge patients to tell their providers if they smoke, have heart problems or suffer from diseases that increase the risk of heart disease, such as high blood pressure, high cholesterol or diabetes.

Search: Ziagen, Ezpicom, Trizivir, abacavir, HLA-B*5701, GlaxoSmithKline

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