FDA Recommends Pulling Propoxyphene Products, Darvon and Darvocet

One of the makers of pain medications Darvon and Darvocet will stop marketing the drugs after new studies showed they can create abnormal heart rhythms even at normal doses, The Wall Street Journal reported Nov. 20.

Propoxyphene is the active ingredient in Darvon, which was first marketed in 1957. Darvocet contains propoxyphene and acetaminophen. Both were developed by Eli Lilly & Company, which no longer makes either drug. Currently, generic drugs companies, such as Xanodyne Pharmaceuticals and Qualitest/Vintage Pharmaceuticals, produce them instead.

The drugs are popular: in 2009, doctors prescribed Darvon and Darvocet over 10 million times. Safety concerns have dogged propoxyphene for decades, but have previously been linked to patients who exceeded the recommended doses.

The Food and Drug Administration (FDA) kept the drug on the market in 2009 although a panel of experts who performed a safety review voted 14-12 against doing so. Last year, the FDA required drug-makers to add what The Wall Street Journal called “the agency's toughest warning” to packaging, which stated that taking too much of the drug could be fatal. 

The agency also insisted that Xanodyne study the effects of the drug on the electrical system of the heart in healthy patients who took only the prescribed doses. The initial results of the study, released in August and October, caused the agency to recommend against further use of the drug.

According to an FDA announcement, the new study showed that using propoxyphene caused “significant changes to the electrical activity of the heart.” Those changes are linked to potentially deadly abnormal heart rhythms.

An FDA official explained in a memo (PDF) that “it is not possible to monitor for, or mitigate, the risk of a fatal cardiac arrhythmia that may occur within the recommended dosing range for propoxyphene.”

Gerald Dal Pan, who directs the FDA's Office of Surveillance and Epidemiology, said, “With the new study results, for the first time we now have data showing that the standard therapeutic dose of propoxyphene can be harmful to the heart.”

In response, Xanodyne agreed to remove Darvon and Darvocet from the market, and the FDA will ask other drug-makers to follow suit.

Drugs containing propoxyphene are already in the process of being removed from the European Union in phases, following a 2009 recommendation from the European Medicines Agency.