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Dextropropoxyphene chemical structure

[(2R,3R)-4-dimethylamino- 3-methyl-1,2-diphenyl-butan-2-yl] propanoate
IUPAC name
CAS number
ATC code


Chemical formula {{{chemical_formula}}}
Molecular weight 339.471 g/mol
Bioavailability {{{bioavailability}}}
Metabolism {{{metabolism}}}
Elimination half-life 3.6–6.5 hours[1]
Excretion {{{excretion}}}
Pregnancy category C, D for prolonged use (US)
Legal status Schedule IV (in dosage form) (US)
Routes of administration oral

Dextropropoxyphene is an analgesic in the opioid category. It is used to treat mild to moderate pain and as an anti-tussive. It can be used to ease surgical pain both prophylactically and palliatively. It is possible to classify it as a mild opioid pain-killer, however it is considered no more effective than aspirin in treating pain.[2]

Dextropropoxyphene is sometimes combined with paracetamol (acetaminophen) or aspirin. Trade-names include Darvocet-N for dextropropoxyphene and paracetamol and Darvon-N with ASA for dextropropoxyphene and aspirin.[3][4] It is also sometimes sold in combination with caffeine in order to prevent abuse & boost pain control.[2][5]

There is no peer-reviewed evidence that this combination is any more effective than paracetamol alone. There is significant anecdotal evidence from patients that Darvocet is more effective than paracetamol, but a third of patients suffering chronic pain report relief from that pain when treated with placebo.

It is manufactured and marketed by Eli Lilly and Company.

It is an optical isomer of levopropoxyphene. The racemic mixture is called propoxyphene.

Some preparations that contain dextropropoxyphene include Distalgesic and Doloxene.



Dextropropoxyphene, like codeine, is an opioid. Codeine is more commonly used; however, some individuals (approximately 10-20% of the Caucasian population) are unable to metabolize it, due to poor functioning of the enzyme CYP2D6. It is in these people that dextropropoxyphene is particularly useful, as its metabolism does not require CYP2D6.

Restless Legs Syndrome (RLS)

Propoxyphene has been found to be helpful in relieving the symptoms of Restless legs syndrome (RLS).

Opioid withdrawal

In pure form, dextropropoxyphene is commonly used to ease the withdrawal symptoms in people addicted to opioids. Being very weak in comparison to the opioids that are commonly abused, dextropropoxyphene can only act as a "partial" substitute. It does not have much effect on mental cravings; however it can be effective in alleviating physical withdrawal effects, such as muscle cramps.

Dextropropoxyphene is subject to some controversy: while many physicians prescribe it for a wide range of mildly to moderately painful symptoms as well as for treatment of diarrhea, many others refuse to prescribe it, citing limited effectiveness.


The therapeutic index of dextroproxyphene is relatively small. In the UK, dextropropoxyphene and co-proxamol are now discouraged from general use; and, since 2004, preparations containing only dextropropoxyphene have been discontinued. This has been a somewhat controversial decision, since it has caused abusers to switch to the combined product and risk paracetamol toxicity. Australia declined to follow suit and opted to allow pure dextropropoxyphene to remain available by prescription. From 31st December 2007, in the UK co-proxamol is only available on a named patient basis, for long term chronic pain and only to those who have already been prescribed this medicine. Its withdrawal from the UK market is a result of concerns relating to its toxicity in overdose (even small overdose can be fatal), and dangerous reaction with alcohol. Recreational use in the UK is uncommon. Many patients have been prescribed alternative combinations of more potent drugs.

In the United States, dextropropoxyphene HCl is available as a prescription formulation with paracetamol (acetaminophen) in ratio anywhere from 30 mg / 600 mg to 100 mg / 650 mg (or 100 mg / 325 mg in the case of Balacet), respectively. These are usually named "Darvocet." On the other hand, "Darvon" is a pure propoxyphene preparation available in the U.S. that does not contain paracetamol. In Australia, dextropropoxyphene is available on prescription, both as a combined product (32.5mg dextropropoxyphene per 325mg paracetamol branded as either "Di-gesic", "Capadex", and "Paradex," it is also available in pure form (100 mg capsules) known as "Doloxene".


Adverse effects

Darvocet overdose is commonly broken into two categories: liver toxicity (from paracetamol poisoning) and dextropropoxyphene overdose. Many users experience toxic effects from the paracetamol (acetaminophen) in pursuit of the endlessly-increasing dose required to achieve euphoria. They suffer acute liver toxicity, which causes severe stomach pains, nausea, and vomiting (all of which are increased by light or stimulation of the sense of sight).

Dextropropoxyphene also has several other non-opioid side-effects.

Both propoxyphene and its metabolite norpropoxyphene, have local anesthetic effects at concentrations about 10 times those necessary for opioid effects. In this respect, norpropoxyphene is more potent than propoxyphene, and they are both more potent than lidocaine.[6]

Both propoxyphene and norpropoxyphene also have direct cardiac effects which include decreased heart rate, decreased contractility, and decreased electrical conductivity (ie, increased PR, AH, HV, and QRS intervals). Norpropoxyphene is several times more potent than propoxyphene in this activity. These effects appear to be due to their local anesthetic activity and are not reversed by naloxone.[6][7][8]

Both propoxyphene and norpropoxyphene are potent blockers of cardiac membrane sodium channels and are more potent than lidocaine, quinidine, and procainamide in this respect.[9]

Propoxyphene and norpropoxyphene appear to have the characteristics of a Vaughn-Williams Class Ic antiarrhythmic.

Darvon, a dextropropxyphene made by Eli Lilly, which had been on the market for 25 years, came under heavy fire in 1978 by consumer groups that said it was associated with suicide. Darvon was never withdrawn from the market, but Lilly has waged a sweeping, and largely successful, campaign among doctors, pharmacists and Darvon users to defend the drug as safe when it is used in proper doses and not mixed with alcohol.

In Sweden physicians have been discouraged by the medical products agency to prescribe dextropropoxyphene due to the risk of respiratory depression when taken with alcohol. [10] Products with other active ingredients have been taken off the market and only products with only dextropropoxyphene are supposed to be sold. Physicians are recommended only to prescribe products with only dextropropoxyphene and not to patients with a history of drug abuse, depression or suicidal tendencies. The combination of dextropropoxyphene HCl and paracetamol sold under the name "Distalgesic" is no longer available in Sweden. Other products sold are "Doloxene" and "Dexofen" both containing dextropropoxyphene napsylate.

In the United Kingdom, the Medicines & Healthcare Regulatory Authority (MHRA) removed the licence for co-proxamol on 31st December 2007. Whilst the MHRA are to be commended for their motivation in trying to reduce the number of suicides through misuse of co-proxamol, the decision has proven controversial twice reaching the rarefied heights of a UK Parliament House of Commons Adjournment Debate. On 13th July 2005[11] and on 17th January 2007.[12] The problem that has arisen is many patients have found alternatives to co-proxamol either too strong, too weak, or with intolerable side effects. During the House of Commons debates, it is quoted that originally some 1,700,000 patients in the UK were prescribed co-proxamol. Following the MHRA phased withdrawal this has eventually been reduced to 70,000. However, it appears this is the residual pool of patients who cannot find alternate analgesia to co-proxamol. To make matters worse, the MHRA safety net of prescribing co-proxamol after licence withdrawal from 31st December 2007 on a "Named Patient" basis where doctors agree there is a clinical need, has been rejected by most UK doctors because the MHRA wording that "responsibility will fall on the prescriber" is unacceptable to most doctors. As a result of many UK citizens now in untreated pain, there are now several patients lining up to raise the collapse of the MHRA "Named Patient" scheme directly with the current Prime Minister Gordon Brown at the Glenrothes By-election with 20,000 leaflets being distributed along with free copies of the book: Letters From The Edge - the Government Coproxamol Scandal being given out during the Wetminster By-election.

Further MHRA References.[13]


Hydrochloride and napsylate salts

Propoxyphene was initially introduced as propoxyphene hydrochloride. Shortly before the patent on propoxyphene expired, propoxyphene napsylate form was introduced to the market. Napsylate salt is claimed to be less prone to abuse, because it is almost insoluble in water and therefore cannot be used for injection. Napsylate also gives lower peak blood level [14]. Because of different molecular mass, a dose of 100 mg of propoxyphene napsylate is required to supply an amount of propoxyphene equivalent to that present in 65 mg propoxyphene hydrochloride.

Toxicologic mechanism

A) Excessive opioid receptor stimulation is responsible for the CNS depression, respiratory depression, miosis, and gastrointestinal effects seen in propoxyphene poisoning. It may also account for mood/thought altering effects.

B) Local anesthetic activity appears to be responsible for the arrhythmias and cardiovascular depression seen in propoxyphene poisoning.[8] Widening of the QRS complex appears to be a result of a quinidine-like effect of propoxyphene, and sodium bicarbonate therapy appears to have a positive direct effect on the QRS dysrhythmia.[15]

C) Seizures may result from either opioid or local anesthetic effects.[6]

D) Pulmonary edema may result from direct pulmonary toxicity, neurogenic/anoxic effects, or cardiovascular depression.[8]


Caution should be used when administering dextropropoxyphene, particularly with children and the elderly and with patients who may be pregnant or breast feeding; other reported problems include kidney, liver or respiratory disorders, and prolonged use. Attention should be paid to concomitant use with tranquilizers, antidepressants or excess alcohol.


Template:Cleanup-jargon Allergy to paracetamol or dextropropoxyphene, alcoholism.

Recreational use

Those who take dextropropoxyphene for recreational purposes take larger than therapeutic doses and, if it is not extracted, the paracetamol (acetaminophen) that is present in combination products can be toxic to the liver. Some adverse effects of recreational dextropropoxyphene use are: a persistent dry mouth, decreased appetite, urinary retention and constipation, and/or diarrhea that may lead to diverticulitis.

Use in Assisted suicide

High toxicity and relatively easy availability made propoxyphene drug of choice for right to die societies. Propoxyphene is listed in Dr. Philip Nitschke's "Peaceful Pill Handbook"[16] and Dr Pieter Admiraal's "Guide to a Humane Self-Chosen Death"[17]. "With the withdrawal of the barbiturate sleeping tablets from the medical prescribing list, propoxyphene has become the most common doctor-prescribed medication used by seriously ill people to end their lives.


  1. Slywka GW, Melikian AP, Whyatt PL, Meyer MC (1975). Propoxyphene bioavailability: an evaluation of ten products. J Clin Pharmacol 15 (8-9): 598–604.
  2. 2.0 2.1 Nursing Drug Handbook, Springhouse, page 324
  3. Nursing Drug Handbook, Springhouse, page 306
  4. The paracetamol combination(s) are known as co-proxamol or in the UK and Capadex or Di-Gesic in Australia.
  5. There is conflicting evidence as to whether it improves pain control. Nursing Drug Handbook, Springhouse, page 419
  6. 6.0 6.1 6.2 Nickander et al., 1984
  7. Bredgaard, Sorensen et al., 1984
  8. 8.0 8.1 8.2 Strom et al., 1985b
  9. Holland & Steinberg, 1979
  10. Fixed combinations of analgesic drugs containing dextropropoxyphene to be removed from the market in the autumn of 2005.
  11. Co-Proxamol: 13 Jul 2005: House of Commons debates (
  12. Co-proxamol: 17 Jan 2007: Westminster Hall debates (
  13. Failure Of MHRA Coproxamol Named Patient System - Visitor Opinion
  14. Wilson, Charles Owens and Gisvold, John H. Wilson and Gisvold's textbook of organic medicinal and pharmaceutical chemistry, Lippincott Williams & Wilkins.
  15. Stork et al., 1995
  16. Nitschke, Philip & Fiona Stewart (2006). The Peaceful Pill Handbook, U.S.: Exit International.
  17. Dr. Pieter Admiraal et al.. Guide to a Humane Self-Chosen Death, The Netherlands: WOZZ Foundation, Delft.

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