Delayed FDA Removal of Painkiller Propoxyphene (DARVON, DARVOCET) From U.S. Market Has Cost More Than 1,000 U.S. Lives

Note: Public Citizen petitioned the FDA in 1978 and 2006 to ban propoxyphene.

The November 2010 announcement by the U.S. Food and Drug Administration (FDA) that propoxyphene-containing products are finally going to be taken off the market is a serious indictment of the FDA’s long-lasting unwillingness to protect people in this country from a deadly but barely effective painkiller.

The FDA banned propoxyphene-containing products (DARVON, DARVOCET) because of dangers that have been known for years. In fact, the drug was banned in the U.K. almost six years ago and in the European Union almost 1.5 years ago.

Evidence going back more than 30 years indicates that propoxyphene is not very effective, is toxic at doses not much higher than the recommend dose (because a heart-toxic metabolite accumulates in the body), and is somewhat addictive. It has been linked to many thousands of U.S. deaths since 1981, a large proportion of which were likely caused by cardiac toxicity, including instances with interruption of electrical conduction in the heart.

In announcing its ban in 2005, the U.K. stated that the efficacy of propoxyphene “is poorly established and the risk of toxicity in overdose, both accidental and deliberate, is unacceptable” and that “in relation to safety, there is evidence that fatal toxicity may occur with a small multiple of the normal therapeutic dose and a proportion of fatalities are caused by inadvertent overdose.” Thus the FDA’s claim that this is the first evidence that the drug is dangerous at the “standard therapeutic dose” rings dangerously hollow.

The FDA’s deadly delay in this case starkly illustrates how one of the most important public health concepts, the precautionary principle, was embraced by the U.K. and EU, but was for too long recklessly rejected by the FDA.

Since the January 2005 announcement of the U.K.’s phased, two-year withdrawal of this drug (followed by an immediate steep decline in use), approximately 120 million retail prescriptions have been filled in the U.S. for propoxyphene-containing drugs. These include DARVOCET, which contains propoxyphene and acetaminophen, DARVON and generic versions of the drug.

Due to FDA negligence, at least 1,000 to 2,000 (or more) people in the U.S. have died from using propoxyphene since the time the U.K. ban was announced. The best forensic data — the kind relied upon for the U.K. and European bans, come from Florida, where routine drug testing is required as part of many autopsies. Deaths are categorized as being “caused” by a particular drug if the amount of the drug found in the body is above a certain level.

From 2005 through 2009, in Florida alone, 395 deaths were caused by propoxyphene. If data from 2007 are representative, about 78 percent of the Florida deaths caused by propoxyphene
were ruled accidental.

After the U.K. ban, Public Citizen again petitioned the FDA in February 2006 to ban the drug. The petition did not even result in an FDA advisory committee hearing until we sued the agency in 2008 to force it to respond. The subsequent January 2009 FDA advisory committee hearing resulted in a 14-12 vote in favor of banning propoxyphene, despite some FDA efforts to sway the committee against voting for a ban. In July 2009, several weeks after the European Medicines Agency announced its ban, the FDA denied our petition to ban the drug.

The FDA’s excuse — that it needed to order a human study to find that “the drug puts patients at risk of potentially serious or even fatal heart rhythm abnormalities” before deciding whether to ban propoxyphene — only emphasizes how out-of-step the agency is with the rest of the world, which already had enough human evidence of death and near-death in tens of thousands of people to act accordingly.

In a study on dogs published 31 years ago, researchers at Lilly, the discoverer of propoxyphene, stated that “cardiac conduction depression may be a factor in some of the [human] cardiac toxicities associated with propoxyphene overdose.” This study examined the same kind of functions measured in the human study being put forth by the FDA as a justification for belatedly banning propoxyphene.

We will ask for and support a congressional investigation into who in the FDA, specifically in the Center for Drug Evaluation and Research, was responsible for the loss of so many lives in this country. It is clear that long before 2010, many drug safety experts in the Office of Surveillance and Epidemiology had decided the drug should be removed from the market.