November 19, 2010
The U.S. Food and Drug Administration (FDA) announced today that the agency has requested manufacturers of propoxyphene, brand name Darvon, Darvocet and its generic equivalents, be voluntarily withdrawn from the market due to serious and fatal heart risks.
Physicians prescribe propoxyphene, an opioid analgesic, for the treatment of mild to moderate pain, such as pain associated with arthritis. Pharmacies filled more than 23.3 million prescriptions for propoxyphene in 2007. It is one of the top 40 most commonly prescribed drugs.
Recent clinical data has shown that people who take propoxyphene are at risk of potentially serious or even fatal heart rhythm abnormalities, called arrhythmia. This study showed that, even when taken at recommended doses, propoxyphene causes significant changes to the electrical activity of the heart visible on an electrocardiogram (EKG). These changes in electrical activity can increase the risk for abnormal heart rhythms linked to serious adverse effects, including sudden death. The data also indicated that the risk of these cardiac events for any particular patient (even patients who have taken the drug for many years) is subject to change based on small changes in the health status of the patient, such as dehydration, a change in medications, or decreased kidney function.
The FDA weighted this information along with other information, including new epidemiological data, and concluded that the risks of propoxyphene outweigh the benefits.
“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,” said Gerald Dal Pan, M.D., M.H.S., director of the Office of Surveillance and Epidemiology, CDER.
Xanodyne Pharmaceuticals Inc, the maker of brand name Darvon and Darvocet, has agreed to withdraw the drug from the U.S. market and the FDA has notified manufacturers of generic propoxyphene products of Xanodyne’s decision, requesting they do the same.
“This withdrawal is part of a market-wide withdrawal applying to all propoxyphene-containing products, affecting branded and generic pharmaceutical companies and a number of products on the market,” said Xanodyne in a press release.
“The FDA is pleased by Xanodyne’s decision to voluntarily remove its products from the U.S. market,” said John Jenkins, M.D., director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research (CDER) in an FDA release. “These new heart data significantly alter propoxyphene’s risk-benefit profile. The drug’s effectiveness in reducing pain is no longer enough to outweigh the drug’s serious potential heart risks.”
Propoxyphene has also been associated with suicide and unintentional overdose.
In 1978, the consumer advocacy group Public Citizen petitioned the FDA to withdraw the drug from the market claiming “cardiotoxic” effects caused many of the deaths. However, the FDA declined to act.
The United Kingdom ordered a phased withdrawal of propoxyphene from the UK market in 2005.
In January 2009, an FDA advisory committee reviewed efficacy and safety of propoxyphene. The committee voted 14 to 12 against leaving propoxyphene products on the market.
In June 2009, the FDA decided against the recommendation of the advisory committee and instead decided to require that manufacturers strengthen the label, including the boxed warning, and include a medication guide emphasizing the potential for overdose when using these products. At that time, the FDA also required a new safety study to assess the effects of propoxyphene on the heart.
In July 2009, the FDA denied a 2006 Public Citizen petition requesting a phased withdrawal of propoxyphene.
Also in the summer of 2009, the European Medicines Agency (EMEA), the European equivalent of the FDA, recommended and instituted a phased withdrawal of propoxyphene across the European Union.
Originally developed by Eli Lilly & Co. and approved by the FDA in 1957, various drug companies have sold propoxyphene under the following names:
Stand Alone Propoxyphene
Propoxyphene Combination Products
- Balacet (containing Acetaminophen and Propoxyphene)
- Darvocet A500 (containing Acetaminophen and Propoxyphene)
- Darvocet-N (containing Acetaminophen and Propoxyphene)
- Darvon Compound 32 (containing Aspirin, Caffeine, and Propoxyphene)
- Darvon Compound-65 (containing Aspirin, Caffeine, and Propoxyphene)
- PC-CAP (containing Aspirin, Caffeine, and Propoxyphene)
- Propacet (containing Acetaminophen and Propoxyphene)
- Propoxyphene Compound 65 (containing Aspirin, Caffeine, and Propoxyphene)
- Wygesic (containing Acetaminophen and Propoxyphene)
“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 function measured in the human study now being put forth by the FDA as a justification for belatedly banning propoxyphene,” said Public Citizen in response to the FDA withdrawal of propoxyphene for cardiac risks.
Public Citizen estimates that propoxyphene caused 1,000-2,000 or more deaths in the United States since the UK withdrawal in 2005. The organization says that drug testing during autopsies by the medical examiner offices in Florida shows that the propoxyphene caused 395 deaths between 2005 and 2009 in Florida alone.
“The announcement by the U.S. Food and Drug Administration (FDA) that propoxyphene-containing products are finally going to be taken off the market – because of dangers previously known and acted upon, with bans announced in the UK almost six years ago, and in Europe, almost 1½ years ago – is a serious indictment of the FDA’s long-lasting unwillingness to protect people in this country from a deadly but barely effective painkiller,” said Dr. Sidney Wolfe, Director of Public Citizen’s Health Research Group. “We will ask for and support a congressional investigation into whom in the FDA, specifically in the Center for Drug Evaluation and Research, was responsible for the loss of so many lives in this country.”