Propoxyphene was a synthetic opioid medication first approved by the U.S. Food and Drug Administration (FDA) in 1957 for the treatment of mild to moderate pain. It was widely recognized and often prescribed under the brand names Darvon (alone) or Darvocet (combined with acetaminophen). However, propoxyphene is no longer legally manufactured, sold, or prescribed in the United States or in most international markets due to serious safety risks that ultimately outweighed its therapeutic benefits.
Propoxyphene’s Function and Common Applications
Propoxyphene’s active component, dextropropoxyphene, acted as an agonist at the mu-opioid receptor, the primary target for most opioid analgesics. This interaction helped to increase the patient’s tolerance for pain.
The medication was a weak opioid, less potent than substances like codeine, hydrocodone, or morphine. It was reserved for pain too intense for over-the-counter medications like nonsteroidal anti-inflammatory drugs (NSAIDs) but not severe enough to require a stronger prescription opioid. The drug was classified as a Schedule IV controlled substance. In its most popular formulation, Darvocet, it was combined with acetaminophen, which provided an additional non-opioid pathway for pain relief.
Cardiac Safety Concerns Leading to Discontinuation
The primary factor driving the drug’s withdrawal was the discovery of significant cardiac toxicity. While earlier concerns focused on fatal overdose and addictive properties, a specific FDA-mandated study revealed a previously unrecognized danger to the heart’s electrical system.
This post-marketing study, involving healthy volunteers, demonstrated that propoxyphene caused changes visible on an electrocardiogram (ECG). These changes included the prolongation of the PR interval, the widening of the QRS complex, and a lengthening of the QT interval. The QT interval measures the time it takes for the heart’s ventricles to recharge between beats.
An increase in the QT interval can lead to Torsades de Pointes, a life-threatening, irregular heart rhythm that can cause sudden cardiac death. Researchers found that propoxyphene’s metabolite, norpropoxyphene, disrupted the heart’s normal electrical conduction. The data confirmed that the risk of serious or fatal heart rhythm abnormalities was present for all users. The agency concluded that the minimal pain relief provided by propoxyphene no longer justified the risk of serious cardiac events.
The Complete Withdrawal and Current Availability Status
The removal of propoxyphene began in 2009 when the European Medicines Agency recommended the phased withdrawal of the medication across the European Union due to safety concerns. In July 2009, the FDA required manufacturers to add a boxed warning to propoxyphene labels, alerting users to the risk of fatal overdose, and mandated the new safety study on cardiac effects.
Based on the conclusive results of that study, the FDA requested the complete market withdrawal of propoxyphene in November 2010. The agency advised healthcare professionals to immediately stop prescribing propoxyphene-containing products, including brand names like Darvon and Darvocet, as well as their generic versions.
Propoxyphene is no longer available for legal manufacture, sale, or prescription in the United States. Patients who previously relied on the drug were advised to consult their doctors to transition to safer pain management alternatives. These alternatives often include non-opioid options, such as stronger NSAIDs, or other opioid medications like tramadol or combination products containing hydrocodone for similar pain profiles.