Plavix Black Box Warning Questioned by New Study

A new study questions whether the FDA made the right move in requiring a “black box” warning on the blood thinner Plavix, which indicates that some people have a gene that may make the drug less effective.

According to research published in the Journal of the American Medical Association, people with the CYP2C19 alleles genetic variant may suffer no more cardiovascular events on Plavix than those without the gene that took the drug. However, the researchers confirmed that there was a link between the gene and Plavix effectiveness.

Plavix (clopidogrel) is a blood thinner that prevents blood platelets from sticking together to form clots. It is a blockbuster medication, generating annual sales of over $6 billion for Bristol Myers Squibb Co. and Sanofi-Aventis.

In August 2009, researchers from the University of Maryland identified a gene variant found in about one-third of the population that may signal a reduced effectiveness of Plavix.

In March 2010, the FDA warned that people with the CYP2C19 variant have reduced functioning of a liver enzyme that is supposed to convert Plavix from its inactive form to its active form, potentially making Plavix ineffective at reducing the risk of blood clots. The agency required Plavix to carry a black box warning, the strongest labeling warning the FDA can require.

The new research looked at 32 studies involving about 42,000 patients and found that while the ability to metabolize Plavix was affected by the CYP2C19 gene variant, that did not appear to translate into more heart attacks. The researchers said previous studies indicating an increased risk of Plavix heart attacks for patients with the gene variant may have been skewed by small sample sizes and selective outcome reporting. As a result, the study calls into question the FDA’s decision to place a black box warning on Plavix.

A number of Plavix lawsuits have been filed against the manufacturers alleging that the makers of Plavix promoted the expensive medication as a safer alternative to aspirin, although it may actually provide no benefit over taking a four-cent-a-day aspirin. Plaintiffs allege that they suffered injuries as a result of their unnecessary use of Plavix, such as gastrointestinal bleeding, severe ulcers, heart attacks, strokes and a rare blood disorder known as TTP, or thrombotic thrombocytopenic purpora.

Plaintiffs allege that the drug makers repeatedly overstated the safety and effectiveness of Plavix, and point out that the companies were repeatedly cited by the FDA for illegal, off-label promotions and for ads and campaigns that touted its benefits over aspirin and how safe it was for the stomach; both claims that the FDA said were unproven.