QTc interval prolongation by d-propoxyphene: what about other analgesics?

d-Propoxyphene, which was previously available in many single-agent and combination products, was recently voluntarily withdrawn from the US market following an FDA recommendation based partly on the concern that the risk associated with QT prolongation exceeded the clinical benefit of the drug. The drug had previously been withdrawn from European markets. These recent actions prompt the question: what is known about QT prolongation and analgesic drugs?

A systematic search was conducted of 50 opioid and non-opioid analgesic drugs using PubMed, the FDA website, and the Internet. Search terms for opioids, NSAIDs, acetaminophen and other analgesics were used (including both generic and brand names), along with QTc, QTc prolongation, QTc interval, hERG, torsades de pointes (TdP), ventricular arrhythmias, and other relevant terms.

There is a paucity of available information on the QT interval for most analgesics. Of those for which there is a lot of data, only methadone, oxycodone, and LAAM (levo--acetylmethadol) appear to have a known and accepted level of effect on the QT interval.