Propoxyphene is an opioid medication that was first approved by FDA in 1957. It has been marketed in the United States since 1976 as a Schedule IV Controlled Substances used as either a single ingredient (e.g., Darvon) or in combination with acetaminophen (e.g., Darvocet) to treat mild to moderate pain. Since 1978, FDA has received two citizen petitions asking FDA to remove propoxyphene from the market or to reschedule the drug from Schedule IV to Schedule II (moving from a category of drugs with less likelihood of dependence and a low potential for abuse to a more restricted category reserved for more potent drugs). Based on all evidence available, FDA previously concluded that the benefits of propoxyphene for pain relief at recommended doses outweighed the safety risk and that neither withdrawal nor changes in scheduling were warranted.
In January 2009, the FDA held an advisory committee meeting to address the efficacy and safety of propoxyphene. The committee voted 14 to 12 against the continued marketing of propoxyphene products but noted that additional information about the drug’s cardiac effects would be relevant in weighing its risks and benefits.
In July 2009, the FDA decided to permit continued marketing of propoxyphene with a new boxed warning added to the drug label alerting patients and health care professionals to the risk of a fatal overdose. Meanwhile, Xanodyne conducted a study in healthy volunteers to determine an appropriate dose that could be used in the definitive cardiac study. Data from that study demonstrated that even when propoxyphene was taken at recommended doses, there were significant changes to the electrical activity of the heart including prolonged PR interval, widened QRS complex and prolonged QT interval.
In light of these new scientific findings, FDA determined the post-marketing safety signals for this drug have taken on new importance, and the overall balance of risk and benefit can no longer be considered favorable. The agency is recommending that propoxyphene products be removed from the US market.