Propoxyphene (dextropropoxyphene): a critical review of a weak opioid analgesic that should remain in antiquity

Am J Ther. Nov-Dec 2006;13(6):534-42. doi: 10.1097/01.mjt.0000253850.86480.fb.

Abstract

Propoxyphene (dextropropoxyphene) is a synthetic weak opioid introduced into the United States in 1957. It is most frequently prescribed in combination with acetaminophen and/or aspirin. After its ubiquitous introductory phase, it was soon discovered that this drug's iatrogenic events (cardiotoxicity, seizures, etc.) far outweighed any perceived therapeutic benefit. Propoxyphene analgesia was equated with that of merely acetaminophen or aspirin independently. The propoxyphenes euphorigenic component has created a problem in its prescribing. Use of this agent in the elderly should be avoided because of its complex pharmacokinetics and pharmacodynamics. The pharmacokinetics, pharmacodynamics, and pharmacology of this drug are discussed thoroughly in this article, including its arrhythmogenicity. Additional noncardiovascular pharmacotherapies that produce QTc prolongation or arrhythmogenicity are described. A list of the cytochrome P450 2D6 pharmacotherapies that will interact with propoxyphene is provided in the article. The use of this agent is highly discouraged. The rationale for this is discussed fully within this article. The toxicity of this drug is partially related to nor-propoxyphene a non-opioid cardiotoxic metabolite. The mere warnings of fatalities within the package insert should alert any cautious prescriber on the dangers of this agent and dampen its prescribing potential.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacokinetics
  • Analgesics, Opioid / therapeutic use
  • Arrhythmias, Cardiac / chemically induced*
  • Dextropropoxyphene / adverse effects*
  • Dextropropoxyphene / blood
  • Dextropropoxyphene / pharmacokinetics
  • Dextropropoxyphene / therapeutic use
  • Drug Interactions
  • Drug Labeling
  • Drug Prescriptions
  • Humans
  • Opioid-Related Disorders*
  • Risk Assessment
  • Seizures / chemically induced

Substances

  • Analgesics, Opioid
  • Dextropropoxyphene