It is Time to Remove Propoxyphene from Clinical Practice

On January 30, two Food and Drug Administration (FDA) advisory committees voted to remove propoxyphene from the market. They concluded that the risks associated with propoxyphene outweigh the potential benefits. The committees cited a lack of adequate clinical data supporting the efficacy of propoxyphene as well as with safety concerns regarding cardiotoxicity, chronic use, and use in the elderly. The FDA panel recommended banning both single ingredient propoxyphene salts (Darvon) and the combination dosage form propoxyphene napsylate and acetaminophen (Darvocet) as a culmination of a long-standing attempts by critics of the analgesics based on allegations of frequent intentional and unintentional overdosing. The nonprofit consumer advocacy organization Public Citizen, a frequent critic of the pharmaceutical industry, petitioned the FDA to withdraw the drug.¹ In its petition, Public Citizen referenced the federal Drug Abuse Warning Network that lists propoxyphene in 5.6% of drug-related deaths between 1981 and 1999. The petitioner also said the network reported 2110 accidental to propoxyphene-related deaths over the same period. The FDA Safety Office said it had searched the agency's database of reported drug problems, but the result was ‘insufficient’ to allow reviewers to make a clear-cut recommendation. That office found more than 3000 reports of serious problems. Options open to the FDA include banning the drug, requiring more explicit label warnings, requiring safety studies, and education of prescribers and consumers. No major pharmaceutical manufacturer makes or distributes propoxyphene in the United States any longer. The two companies that market propoxyphene in this country are Xanodyne Pharmaceuticals and Qualitest/Vintage Pharmaceuticals. Both continue to posit that the drug is safe and effective when used as directed. The companies filed documents with the FDA saying that doctors need a range of options to treat pain and noting that other pain relievers also are abused.

We reject that claim. This Journal has long been critical of propoxyphene. A 2003 article on pharmacotherapy in long-term care facilities expressed concern about propoxyphene safety in elderly patients.² In 2006, the Journal reported on the withdrawal of the propoxyphene-paracetamol (acetaminophen) from clinical use in the United Kingdom that was promulgated by the Committee on the Safety of Medicines of the UK.³ And in 2007, a response in the European Discussion Forum by Dr. Elon Eisenberg commented on safety concerns with the drug of the drug.⁴

Although some patients who have taken propoxyphene for years may still wish to use it, we have safer and more effective alternatives. The risk to benefit ratio for propoxyphene is not favorable. Unfortunately, many primary care providers continue to prescribe this outdated drug. More knowledgeable clinicians should help to educate these colleagues. It is time for it to be removed from clinical use.