Indications

Analgesia
Dextropropoxyphene, like codeine, is a weak opioid, known to cause dependancy among recreational users. Codeine is more commonly used; however, as codeine is, in essence, a prodrug that requires in vivo metabolism to the more active opioid morphine for maximum efficacy, it is ineffective for some individuals with the "poor metabolizer" genotype of the liver Cytochrome P450 enzyme CYP2D6. It is in people with this low-function isoform of the CYP2D6 gene 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.

Contraindications
Allergy to paracetamol or dextropropoxyphene; alcoholism; combination with amphetamine. Not intended for use in patients who are prone to suicide or addiction.

Toxicity
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).

An overdose of dextropropoxyphene may lead to various systemic effects. 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.

In addition, both propoxyphene and its metabolite norpropoxyphene, have local anesthetic effects at concentrations about 10 times those necessary for opioid effects. Norpropoxyphene is a more potent local anesthetic than propoxyphene, and they are both more potent than lidocaine.[5] Local anesthetic activity appears to be responsible for the arrhythmias and cardiovascular depression seen in propoxyphene poisoning.[6]

Both propoxyphene and norpropoxyphene are potent blockers of cardiac membrane sodium channels and are more potent than lidocaine, quinidine, and procainamide in this respect.[7] As a result, propoxyphene and norpropoxyphene appear to have the characteristics of a Vaughn-Williams Class Ic antiarrhythmic.

These direct cardiac effects include decreased heart rate (i.e. cardiovascular depression), decreased contractility, and decreased electrical conductivity (ie, increased PR, AH, HV, and QRS intervals). These effects appear to be due to their local anesthetic activity and are not reversed by naloxone.[5][6][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.[9]

Seizures may result from either opioid or local anesthetic effects.[5]. Pulmonary edema may result from direct pulmonary toxicity, neurogenic/anoxic effects, or cardiovascular depression.[6]

Available forms
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 [10]. 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.

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 (32.5 mg dextropropoxyphene per 325 mg paracetamol branded as either "Di-gesic", "Capadex", and "Paradex," it is also available in pure form (100 mg capsules) known as "Doloxene".

Recreational use
Those who take dextropropoxyphene for recreational purposes take larger than therapeutic doses. However, 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.
 

Trade Name:

Doloxene - 100 mg - dextropropoxyphene napsylate
 Use by right to die societies
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"[11] and Dr Pieter Admiraal's "Guide to a Human Self-Chosen Death"[12]. "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." [11]. Slang name for the combination of propoxyphene and other drugs used for suicide is "Darvon cocktail".[13]

Usage Controversy and Regulation
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.[citation needed] In addition, the therapeutic index of dextroproxyphene is relatively small.

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.

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.[citation needed] 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.
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