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WARNINGDANGER OF DEATH
High doses alone or ordinary doses in combination with other depressants can fatally stop breathing.
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Dextropropoxyphene
4-(Dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl propanoate
Propoxyphene, Darvon, Darvocet, Co-proxamolOpen in Piru
Dextropropoxyphene is an opioid analgesic in the phenylpropylamine chemical class and has depressant effects. It is the analgesic optical isomer of levopropoxyphene1. It is also reported to have antitussive2 and local anaesthetic actions2. Developed through U.S. Navy- and CIA-funded research, it was used for mild pain. In 2010, FDA concluded that propoxyphene's risks outweighed its benefits as a pain reliever after receiving data showing a risk of potentially serious or fatal heart rhythm abnormalities at therapeutic doses, along with other information.3
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Threshold~30 mg
Light30-65 mg
Moderate65-100 mg
Strong100-200 mg
Heavy200+ mg
Duration
Onset20-30 minutes
After Effects1-6 hours
Total1-3 hours
Subjective Effects
Subjective Effects not written up yet
Pharmacology
Pharmacodynamics
Dextropropoxyphene is a weak opioid receptor agonist, acting primarily at mu-type receptors in the central nervous system.2 Opioid receptor activation inhibits adenylate cyclase and reduces intracellular cAMP, while closing N-type calcium channels and opening inwardly rectifying potassium channels, which decreases neurotransmitter release and neuronal excitability.4 It also acts as an agonist at delta-type receptors, an antagonist at kappa-type receptors and NMDA receptors, and a potent noncompetitive antagonist at α3β4 neuronal nicotinic acetylcholine receptors. Sodium-channel inhibition and a local anesthetic effect observed in vitro for propoxyphene and norpropoxyphene5 are additional actions.
Pharmacokinetics
Propoxyphene is metabolized primarily in the liver by CYP3A4-mediated N-demethylation to norpropoxyphene. The metabolite is excreted by the kidneys; approximately 20% to 25% of an administered dose is recovered in urine within 48 hours, mostly as free or conjugated norpropoxyphene. The reported elimination half-life is 6-12 hours, with a volume of distribution of 16 L/kg and clearance of 2.6 L/min.5
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
1,2-BenzodiazepineAbametapirAbataceptAbemaciclibAbiraterone
Tolerance
Tolerance not written up yet
Harm Potential
Addiction & Dependence
Psychological
ModerateClassified as habit-forming with documented addictiveness. The FDA advisory committee cited addictiveness as one of the concerns leading to market withdrawal recommendations.
Physical
ModerateRegular opioid use can produce physical dependence. Prescribers were cautioned against giving dextropropoxyphene to people with prior substance-use problems.
Toxicity
Cardiotoxicity occurs even at doses close to therapeutic levels, with risk of fatal cardiac arrhythmias; this was the primary reason for market withdrawal.
Respiratory depression is a significant risk, particularly when combined with alcohol, and can be fatal.
Hepatotoxicity, liver failure, and necrosis can occur, particularly in combination products containing paracetamol and especially in individuals with pre-existing liver damage from alcohol use.
CNS depression including coma can occur in overdose; balance disorder with risk of falls from standing height has been reported.
Seizure Risk
Propoxyphene poisoning is associated with a higher seizure rate than intoxication from other opiates. These seizures may reflect opioid activity, local anesthetic effects, or, when amphetamines are involved, a risk of fatal convulsions.
History & Culture
Development and medical use
Dextropropoxyphene was successfully tested in 1954 during US Navy- and CIA-funded research seeking nonaddictive substitutes for codeine. It was patented in 1955 and manufactured by Eli Lilly and Company for the treatment of mild pain. The drug was marketed under names including Darvon, Darvocet-N,
Legality
International
Withdrawn from markets in Europe and the United States.
By Country
Illegal2
United StatesIllegalUnder United States federal law, bulk dextropropoxyphene in non-dosage form is listed in Schedule II, while dextropropoxyphene dosage forms are listed in Schedule IV, under 21 C.F.R. §§ 1308.12(c)(5) and 1308.14(b)(2). Possession is unlawful unless obtained by valid prescription or otherwise authorized; unauthorized manufacture, distribution, dispensing, and possession with intent to carry out those activities are also unlawful. The FDA withdrew approval of identified propoxyphene drug applications, but that action did not remove dextropropoxyphene from the federal controlled-substance schedules.
CanadaIllegalDextropropoxyphene is expressly listed within the phenalkoxams class in Schedule I, item 7(3) of the Controlled Drugs and Substances Act; item 7 also covers the class's salts, derivatives, and salts of derivatives. The Act prohibits unauthorized possession, trafficking, possession for trafficking, import, export, and production of Schedule I substances. Health Canada's Drug Product Database records branded, generic, and combination dextropropoxyphene products as Cancelled Post Market and identifies them as NARCOTICS (CDSA I). SOR/2025-243 will restate the same Schedule I subitem on October 1, 2026, when the Controlled Substances Regulations, SOR/2025-242, will also place the substance in Schedule 1 (Narcotics); neither pending instrument changes the current Schedule I classification.
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