Darvon and Darvocet (propoxyphene) — the “Weak Opioid” That Poisoned Hearts, Banned in 2010

When the U.S. Food and Drug Administration asked manufacturers to pull propoxyphene from the American market on 19 November 2010, it was retiring a painkiller that Eli Lilly had introduced in 1957 and that had been prescribed to tens of millions of people across two regulatory generations; the documented record shows the agency acted only after a study it had itself ordered proved the harm, and decades after the first petition to ban the drug was filed. Propoxyphene — marketed alone as Darvon and combined with acetaminophen as Darvocet — was promoted for half a century as a mild, well-tolerated opioid for moderate pain. The gap between that gentle reputation and the molecule’s actual pharmacology was the whole story: at or near ordinary therapeutic doses the drug prolonged the PR interval, widened the QRS complex, and lengthened the QT interval, the electrocardiographic signature of a compound that can stop a heart.

The harm was not subtle and not new. Propoxyphene blocks cardiac sodium channels more potently than the antiarrhythmic agents lidocaine, quinidine, and procainamide, and its long-lived metabolite norpropoxyphene accumulates — especially in the elderly and in patients with impaired kidneys — pushing toxic effects past the point of reversal. The consumer group Public Citizen petitioned the FDA to ban propoxyphene in 1978 and again in February 2006. The drug had been associated with more than 2,000 accidental U.S. deaths since 1981 and ranked among the most common drugs found in fatal overdoses, a mortality profile that prompted the United Kingdom to begin withdrawing the equivalent product, co-proxamol, in January 2005.

The verdict here is therefore plain at the outset: an approved, familiar, “weak” medicine reached enormous populations while the evidence that would eventually condemn it — sodium-channel data, autopsy series, decades of overdose statistics, and a foreign regulator’s reversal — sat fully legible in the literature. The thing that finally moved the FDA was not new theory but a single dedicated experiment: a controlled electrocardiographic study in healthy volunteers, completed in 2010, showing that even at labeled doses propoxyphene measurably deranged cardiac conduction.

What followed the withdrawal was less a courtroom reckoning than a public-health correction visible in the morgue. In the state of Florida, where overdose deaths are tracked closely, fatalities involving propoxyphene fell on the order of 84 percent after the drug left the market — a natural experiment that quantified, in lives, the cost of every year the agency had waited. Propoxyphene became the standard byword for regulatory delay: a case in which the question was not whether a drug was dangerous but how long an agency could decline to answer a petition it had already received twice.