FDA advisory committees recommend ban on Darvon, Darvocet

At a joint meeting of FDA’s Anesthetic and Life Support Drugs and Drug Safety and Risk Management Advisory Committees on January 30, 2009, advisors voted 14 to 12 that propoxyphene and propoxyphene-containing products should be removed from the market.

Propoxyphene (Darvon, Xanodyne; generic propoxyphene) and propoxyphene combinations, including Darvocet (Xanodyne), are used for the treatment of mild-to-moderate acute pain. Propoxyphene is classified as a schedule IV substance.

In 2006, Public Citizen filed a request that FDA begin a phased removal of these agents from the market. In a statement, Sidney M. Wolfe, MD, director of the Health Research Group at Public Citizen, discussed FDA’s efficacy review of this agent, stating, “The FDA review stands on its own merits and, in essence, finds that a) the addition of propoxyphene to acetaminophen does not result in a statistically significant improvement in pain relief compared with acetaminophen alone and b) that propoxyphene alone has only ‘weak analgesic effects.’” Wolfe also pointed to Florida medical examiner data and information from the Drug Abuse Warning Network (DAWN), which collects data from drug-related visits to emergency rooms and drug-related deaths investigated by medical examiners and coroners, to suggest that propoxyphene has been associated with numerous deaths. Wolfe concluded, “Propoxyphene has one of the most unfavorable benefit-to-risk ratios I have ever seen for a drug. This committee will hopefully agree with this and recommend the beginning of a two-year phased withdrawal of these products.”

Xanodyne and Qualitest/Vintage Pharmaceuticals, manufacturers of propoxyphene-containing products, argued in a briefing document, “The diverse nature of pain and the difficulty in appropriately treating it underlies the need to have a wide variety of treatment options, including propoxyphene, available to physicians,” adding, “Like all prescription medications, propoxyphene has risks. However, as a result of propoxyphene’s use for 50 years, practitioners are well aware of these risks. . . . The risks associated with propoxyphene use are adequately disclosed and described in the FDA-approved labeling of propoxyphene drugs.”

In a presentation on behalf of FDA, Joann H. Lee, PharmD, Division of Pharmacovigilance II, and Fatmatta Kuyateh, MD, MS, Division of Epidemiology, discussed the adverse events associated with propoxyphene-containing products. After completing a review of the literature and items reported through the Adverse Event Reporting System (AERS), Lee and Kuyateh found that there was potential association between the agent and the adverse event in some cases, whereas no causal relationship could be established in others. The potential relationship between propoxyphene and cardiotoxicity could likewise not be established. They concluded, however, that “despite current propoxyphene label warnings, narcotic pain relievers and CNS-related drugs continue to be prescribed and used with propoxyphene-containing products, resulting in accidental and intentional deaths.”

FDA has not yet reached a decision regarding whether these products will be removed from the market.