Propoxyphene has been on the market since 1957. It is a widely prescribed member of a group of drugs known as opioids and is used as a treatment for mild to moderate pain. The most frequent side effects of propoxyphene include lightheadedness, dizziness, sedation, nausea, and vomiting.
Like certain other classes of pain medications, propoxyphene products can be addictive and have been linked to deaths in patients, especially when used with alcohol and other drugs. The drug labels' currently warn of those risks. In February, an FDA advisory panel had voted 14-to-12 to withdrawal drugs like Darvon from the market, citing its overdose risks. However, the FDA is not bound to follow the recommendations of its advisory panels.
In addition to the stronger label warnings, the FDA is requiring the manufacturers of these drugs to provide a medication guide to patients stressing the importance of using the drugs as directed.
Propoxyphene manufacturers are required to submit the requested safety labeling changes to the FDA within 30 days, or to provide a reason why they do not believe such changes are necessary. If they do not submit new language, or if the FDA disagrees with the language the companies propose, the Food, Drug, and Cosmetic Act provides strict timelines for discussions regarding the changes. At the end of these discussions, the FDA may issue an order directing the labeling changes as deemed appropriate to address the new safety information.
In addition, the FDA is requiring a new safety study assessing unanswered questions about the effects of propoxyphene on the heart at higher than recommended doses. Findings from this study, as well as other data, could lead to additional regulatory action. To further evaluate the safety of propoxyphene, the FDA plans to work with several groups including the Centers for Medicare & Medicaid Services and the Veterans Health Administration to study how often the elderly are prescribed propoxyphene instead of other pain relievers and the difference in the safety profiles of propoxyphene compared to other drugs.
However, the FDA also said today that it had rejected a petition from the advocacy group Public Citizen requesting a phased withdrawal of propoxyphene. The agency said in its response that despite serious concerns about propoxyphene, the benefits of using the medication for pain relief at recommended doses outweighs the safety risks at this time.
The Public Citizen petition was filed in 2006. In 2008, the group filed a federal lawsuit seeking to force the FDA to act on the petition.
Pubic Citizen petitioned the FDA two years ago to ban Propoxyphene saying it was not any more effective than other, safer painkillers and pointing to at least 2,110 accidental deaths between 1981 and 1999. Several hundred more accidental deaths have been linked to Darvon/Darvocet every year since, according to Public Citizen’s Health Research Group in its petition, which is planned for submission to FDA acting Commissioner Dr. Andrew von Eschenbach. Public Citizen first sought to ban Propoxyphene in 1978.
The lawsuit was filed in US District Court in Washington and argued that the FDA was in legal violation by not ruling on its petition within the required six months. The lawsuit states that Propoxyphen is an addictive narcotic that, even when used properly, can cause slowed heartbeat and other serious cardiac side effects. This February, Public Citizen’s Health Research Group asked the FDA to ban Darvon and Darvocet, two popular painkillers. Dr. Sidney Wolfe, the group’s director, said Propoxyphene, the drugs’ main active ingredient, is a relatively weak painkiller that presents an unacceptable toxic risk to millions of patients taking it annually. “This a black-and-white example of a drug where its risks far outweigh its benefits … there’s no excuse for this drug to be around” said Wolfe.
Prescriptions for the drug—which has been sold since 1957—have decreased, but 23 million prescriptions were still written for propoxyphene-containing drugs last year. Darvocet combines propoxyphene with acetaminophen and is the most popular of these types of painkillers.
An analysis of 26 studies comparing propoxyphene and acetaminophen with just acetaminophen or a placebo found the “narcotic combination offered little benefit over acetaminophen alone” in treating pain. “Thus, propoxyphene provides minimal if any additional analgesia to acetaminophen alone and is associated with significant adverse effects. It cannot be recommended for routine use,” Dr. Carolyn Sachs of the University of California, Los Angeles, wrote in her analysis, published in March 2005 in American Family Physician.
Wolfe said a “phase-out,” meant to wean users from the drug would be followed by a ban, similar to a move in 2005 by the United Kingdom over Co-proxamol, Britain’s most frequently used drug. Co-proxamol was banned over concerns about the high risk of accidental death from slight overdose and its frequent use in suicides. Co-proxamol, is sold under the brand names Distalgesic, Cosalgesic, and Dolgesic in the UK and under the names Darvocet and Darvon in the US.
The body transforms propoxyphene—or codeine—Into norpropoxyphene, which can build up in the body and is associated with a variety of heart problems, including arrhythmia. Propoxyphene is among the nation’s most widely abused painkillers, Substance Abuse and Mental Health Services Administration spokeswoman Leah Young said, adding that a 2004 survey found 21 million people had made “non-medical” use of products containing propoxyphene.