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Ongoing safety review of abacavir, possible MI risk
The Food and Drug Administration (FDA) is updating the public about its ongoing safety review of abacavir and a possible increased risk of heart attack. Abacavir is an antiviral medication used in combination with other antiretroviral drugs for the treatment of HIV-1 infection. Available medications that contain abacavir include Ziagen, Trizivir, and Epzicom.
There has been conflicting information on the potential increased risk of heart attack with abacavir treatment. An increased risk of heart attack (myocardial infarction or MI) has been seen in several observational studies and one randomized controlled trial (RCT) with abacavir. However, an increased risk of heart attack has not been seen in other RCTs and the safety database maintained by the drug manufacturer.
The FDA conducted a meta-analysis of 26 randomized clinical trials that evaluated abacavir. This meta-analysis did not show an increased risk of MI associated with the use of abacavir. Healthcare professionals should continue to prescribe abacavir according to the professional label. Patients should not stop taking their abacavir without first talking to their healthcare professional.
The FDA will continue to communicate any new safety information to the public as it becomes available.
Here's additional information for patients:
Additional Information for Healthcare Professionals:
The FDA's primary objective was to explore the association of abacavir with MI. A literature search was conducted among four databases (International Pharmaceutical Abstracts [IPA], Intelos, Embase and Scopus) for all clinical trials that included a randomized abacavir treatment arm. The FDA manually reviewed the results of the search to identify RCTs that met the following criteria: conducted in adults, sample size greater than 50 subjects, trial status completed, not a pharmacokinetic trial, and not conducted in Africa. The Mantel-Haenszel method, with risk difference, odds ratio (OR), and a 95% confidence interval (CI), was used for the primary analysis based on trial-level summaries; the unit of analysis was the subject, and the stratification factor was the trial. For trials with more than two arms, abacavir versus non-abacavir arms were compared.
Data from 26 RCTs conducted from 1996 to 2010 (16 trials from the drug manufacturer database, 5 from the AIDS Clinical Trials Group (ACTG), and 5 from academic centers were included in the meta-analysis conducted by FDA.) The MI outcomes were reported for 9868 subjects randomized to receive either an antiretroviral regimen that included abacavir or a non-abacavir containing comparison drug regimen. A total of 46 MI events were reported, including 24 MI events from 5028 subjects randomized to an abacavir-containing regimen and 22 MI events from 4840 subjects randomized to a non-abacavir regimen. No statistically significant association between MI and the abacavir-containing regimen was detected (Mantel-Haenszel OR 1.02, 95% CI 0.56 – 1.84). For a review of this meta-analysis, see http://www.retroconference.org/2011/Abstracts/42436.htm
Abacavir sulfate tablets tentatively approved
On March 4, 2011, the Food and Drug Administration (FDA) granted tentative approval for abacavir sulfate scored tablets for oral suspension, 60 mg, indicated in combination with other antiretrovirals for the treatment of HIV-1 infection in pediatric patients. Reviewed under the expedited review provisions of the President's Emergency Plan for AIDS Relief (PEPFAR), this product is manufactured by Cipla Limited of Mumbai, India.
"Tentative approval" means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, but is not eligible for marketing in the U.S. because of existing patent protections. Tentative approval does, however, make the product eligible for purchase outside the United States under the PEPFAR program.
As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility, and of the facilities performing the bioequivalence studies, to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application prior to granting approval or tentative approval to these applications.
You can find a complete list of all Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan on the FDA web site.