AIDS patients should have a genetic test before treatment with GlaxoSmithKline Plc's drug Ziagen to see whether they face a higher risk of a potentially fatal reaction, U.S. regulators said on Thursday.
For patients who test positive for a specific gene variation, Ziagen treatment "is not recommended and should be considered only under exceptional circumstances when the potential benefit outweighs the risk," the Food and Drug Administration said in a notice on its Web site.
Studies found patients with one specific version of an immune system gene had a higher chance of a serious and at-times fatal reaction to Ziagen, the agency said.
Glaxo funded one study that showed testing for the gene variation reduced the incidence of reactions, company spokeswoman Mary Anne Rhyne said. In the study, 5.6 percent of patients tested positive for the variation.
The drugmaker gave the information to the FDA and urged its inclusion in Ziagen's prescribing instructions, Rhyne said.
Black box warning
The recommendation for the screening test is now included in a "black box" on Ziagen's label. A black box is the strongest type of warning for prescription drugs.
The step is another move toward personalized medicine, a drive to determine which drugs work best, or may be harmful, for individual patients.
In Glaxo's study, excluding people with the gene variation cut the reaction rate to 3.4 percent from 7.8 percent.
Based on those findings, it was estimated that 61 percent of patients with the variation would develop the reactions, compared with 4 percent of those without it, the Ziagen label says.
Symptoms of the reactions include fever, rash, nausea, vomiting and fatigue. Severe cases can lead to respiratory failure and death.
Ziagen, known generically as abacavir, had 2007 global sales of $218 million. The drug also is a component of Glaxo's Trizivir, Epzicom and Kivexa AIDS drugs, which had more than $1 billion in combined 2007 sales.
Ziagen's prescribing instructions also include new information about heart risk concerns. The label notes that one study found a higher heart-attack risk for Ziagen-treated patients, but adds that a Glaxo analysis of clinical trials showed "no excess risk."
"In totality, the available data ... are inconclusive," the drug label says.
It urges doctors to be aware of patients' heart disease risk and take steps to minimize contributing factors such as high blood pressure and cholesterol.
