Propoxyphene was an opioid painkiller used to treat mild to moderate pain. It was sold under the brand names Darvon and Darvocet from the 1950s until 2010, when the FDA requested its removal from the U.S. market after new data revealed it could cause dangerous changes to the heart’s electrical activity, even at normal doses.
What Propoxyphene Was Prescribed For
Propoxyphene was classified as a mild opioid pain reliever. Its FDA-approved use was straightforward: relief of mild to moderate pain. Doctors prescribed it for conditions like headaches, dental pain, musculoskeletal injuries, and post-surgical discomfort. It was not intended for severe or chronic pain.
The drug came in two main forms. Darvon contained propoxyphene alone. Darvocet (specifically Darvocet-N) combined propoxyphene with acetaminophen, the same active ingredient in Tylenol, to boost its pain-relieving effect. Darvocet-N 100 contained 100 mg of propoxyphene napsylate and 650 mg of acetaminophen per tablet, typically taken every four hours as needed.
How It Worked
Like all opioids, propoxyphene worked by binding to pain receptors in the brain and spinal cord, dulling the perception of pain. It was considered a weaker opioid compared to drugs like codeine or hydrocodone, which is why it was reserved for milder pain. Despite being weaker, it still carried the core risks of any opioid: drowsiness, dependence with repeated use, and the potential for dangerous respiratory depression in overdose.
Why Propoxyphene Was Pulled From the Market
Concerns about propoxyphene’s safety had been building for decades. The European Medicines Agency concluded that data from forensic centers and national mortality statistics across multiple countries showed a significant number of deaths linked to overdose, while available evidence did not show propoxyphene was more effective than other painkillers already on the market. The UK withdrew its propoxyphene-acetaminophen combination (sold there as co-proxamol) by the end of 2007, and the European Commission ordered all dextropropoxyphene products removed across Europe in June 2010.
The final blow in the U.S. came on November 19, 2010. The FDA announced that a new clinical study had confirmed propoxyphene causes significant changes to the heart’s electrical system at therapeutic doses, not just in overdose. The study found three specific problems: a prolonged PR interval (the time it takes for electrical signals to travel through the upper chambers of the heart), a widened QRS complex (meaning the lower chambers take longer to contract), and a prolonged QT interval (the heart takes longer to reset between beats). At a daily dose of 600 mg, the largest average change in the QT interval was 29.8 milliseconds. At 900 mg daily, it reached 38.2 milliseconds. These changes increase the risk of potentially fatal irregular heart rhythms.
The Problem With Its Metabolite
One of propoxyphene’s most dangerous qualities was what happened after the body began breaking it down. The liver converted it into a byproduct called norpropoxyphene, which lingered in the body far longer than the drug itself. Propoxyphene has a half-life of 6 to 12 hours, meaning it takes that long for half the drug to leave your system. Norpropoxyphene has a half-life of 30 to 36 hours, roughly three times longer.
This metabolite is directly toxic to the heart. It can prolong the electrical signals that coordinate heartbeats and trigger dangerous rhythms, including ventricular fibrillation, where the heart quivers instead of pumping blood. It can also cause fluid buildup in the lungs. Because the kidneys are responsible for clearing norpropoxyphene, anyone with reduced kidney function was at especially high risk of accumulation and toxicity. Older adults faced a double threat: the metabolite’s cardiac effects combined with the drug’s sedating properties, which increased the risk of falls. One large study of over 363,000 patients found that propoxyphene users had roughly twice the risk of hip fracture compared to people not taking any painkillers.
What Replaced Propoxyphene
After propoxyphene’s withdrawal, patients who had been taking it needed alternatives. For mild to moderate pain, the options that remain available are well established and, for many types of pain, at least as effective as opioids.
Over-the-counter options include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, available in both oral and topical forms. For people with ongoing or chronic pain, current guidelines emphasize non-drug approaches alongside medication. These include exercise and physical therapy, cognitive behavioral therapy, acupuncture, massage, and practices like yoga or tai chi. For nerve-related pain, doctors may prescribe certain antidepressants or anticonvulsants that work on pain signaling pathways.
Stronger opioids remain an option when these approaches are not enough, but the shift in pain management since propoxyphene’s era has moved decisively toward using opioids only when the expected benefits clearly outweigh the risks.
Current Availability
Propoxyphene is no longer legally available in any major market. The U.S., UK, and all European Union member states have withdrawn it. If you encounter propoxyphene in an old medicine cabinet, it should not be used and should be disposed of through a pharmacy take-back program. There is no medical situation in which propoxyphene would be recommended over currently available alternatives.