Usage
- Dextropropoxyphene was prescribed for the relief of mild to moderate pain. It was also used as a cough suppressant and had local anesthetic properties.
- Pharmacological Classification: Opioid analgesic.
- Mechanism of Action: Dextropropoxyphene binds to mu-opioid receptors in the central nervous system, inhibiting pain signal transmission and altering pain perception. It also has some activity at kappa-opioid receptors.
Alternate Names
- Propoxyphene (refers to the racemic mixture, but only the dextro- isomer has analgesic effects)
- Brand Names: Darvon (dextropropoxyphene only), Darvocet (dextropropoxyphene and acetaminophen), Di-Gesic, Capadex, Paradex, and Doloxene are among the brand names under which dextropropoxyphene has been marketed, often in combination with paracetamol (acetaminophen). Please note that due to safety concerns, dextropropoxyphene-containing products have been withdrawn from many markets, including the US and Europe.
How It Works
- Pharmacodynamics: Dextropropoxyphene primarily affects the central nervous system by binding to mu-opioid receptors, resulting in analgesia, cough suppression, and potential euphoria. At higher doses, it can cause respiratory depression, sedation, and other opioid-related side effects.
- Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Metabolism: Primarily metabolized in the liver by CYP3A4 and CYP3A5 to nordextropropoxyphene, its major active metabolite. Nordextropropoxyphene has a longer half-life than dextropropoxyphene.
- Elimination: Excreted primarily in the urine.
- Mode of Action: Binds to mu and kappa opioid receptors in the brain and spinal cord. It also inhibits N-methyl-D-aspartate (NMDA) receptors, which may contribute to its analgesic effects. May prolong QTc interval through interactions with several ion channels.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Binds to mu and kappa opioid receptors; inhibits NMDA receptors. Metabolized by CYP3A4 and CYP3A5.
- Elimination Pathways: Primarily renal excretion.
Dosage
Dextropropoxyphene is no longer available in many countries due to safety concerns (cardiac toxicity, overdose risk). The following information is for historical reference only and should not be used for prescribing or administering the drug.
Standard Dosage
Adults: Historically, the usual adult dose was 65 mg dextropropoxyphene hydrochloride or 100 mg dextropropoxyphene napsylate every 4 hours as needed for pain. The maximum recommended dose varies but was often limited to 6 capsules or tablets per day.
Children: Use in children was generally not recommended, and safety and efficacy had not been established.
Special Cases: Dosage adjustments were advised for elderly patients and those with renal or hepatic impairment.
Clinical Use Cases
Dextropropoxyphene was not recommended for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations due to its narrow therapeutic index and risk of serious side effects.
Dosage Adjustments
Dose reductions were necessary for elderly patients and those with renal or hepatic impairment.
Side Effects
Common Side Effects
- Dizziness
- Sedation
- Nausea
- Vomiting
- Constipation
Rare but Serious Side Effects
- Respiratory depression
- Seizures
- Cardiac arrhythmias (including QT prolongation)
- Overdose (potentially fatal)
Long-Term Effects
Adverse Drug Reactions (ADR)
- QT prolongation
- Serotonin syndrome (when combined with serotonergic drugs)
- Respiratory depression
Contraindications
- Hypersensitivity to dextropropoxyphene or acetaminophen
- Patients with significant respiratory depression
- Acute alcoholism
- Suicidal ideation or history of suicide attempts
- Concomitant use of MAO inhibitors
Drug Interactions
- CNS Depressants (alcohol, benzodiazepines, other opioids): Increased risk of respiratory depression and sedation.
- CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): Increased dextropropoxyphene levels and risk of toxicity.
- CYP3A4 Inducers (e.g., carbamazepine, rifampicin): Decreased dextropropoxyphene levels and reduced efficacy.
- Serotonergic Drugs (e.g., SSRIs, MAOIs): Increased risk of serotonin syndrome.
- Warfarin: Increased risk of bleeding.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (older FDA classification; no longer marketed in the US) - Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Dextropropoxyphene is excreted in breast milk. It is recommended to weigh the risks and benefits carefully. Safer alternatives may be preferred.
Drug Profile Summary
- Mechanism of Action: Mu-opioid receptor agonist, kappa-opioid receptor activity, NMDA receptor inhibition.
- Side Effects: Dizziness, sedation, nausea, vomiting, constipation, respiratory depression, seizures, cardiac arrhythmias.
- Contraindications: Hypersensitivity, respiratory depression, acute alcoholism, suicidal ideation, concomitant MAOI use.
- Drug Interactions: CNS depressants, CYP3A4 inhibitors/inducers, serotonergic drugs, warfarin.
- Pregnancy & Breastfeeding: Use with caution; weigh risks and benefits.
- Dosage: Historically 65 mg HCl or 100 mg napsylate every 4 hours, not to exceed maximum daily dose. (No longer marketed in many countries).
- Monitoring Parameters: Respiratory rate, heart rate, blood pressure, ECG (for QT prolongation).
Popular Combinations (Historically, as the drug is no longer marketed in many countries)
- Dextropropoxyphene + paracetamol (acetaminophen): for enhanced analgesia.
Precautions (Historically, as the drug is no longer marketed in many countries)
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dextropropoxyphene?
A: Dextropropoxyphene is no longer recommended or available in many countries due to safety concerns. Historically, the adult dose was 65mg of the hydrochloride salt or 100mg of the napsylate salt every 4 hours as needed, with a maximum daily dose of 390 mg/day (HCl) or 600 mg/day (napsylate).
Q2: What are the serious side effects of Dextropropoxyphene?
A: Serious side effects include respiratory depression, cardiac arrhythmias (including QT interval prolongation), seizures, and overdose, which can be fatal.
Q3: Can Dextropropoxyphene be used during pregnancy?
A: It is not recommended during pregnancy unless absolutely necessary and the benefits clearly outweigh the risks.
Q4: What drugs interact with Dextropropoxyphene?
A: It interacts with CNS depressants (alcohol, benzodiazepines), CYP3A4 inhibitors/inducers, serotonergic drugs, and warfarin.
Q5: What are the contraindications for Dextropropoxyphene?
A: Contraindications include hypersensitivity, significant respiratory depression, acute alcoholism, suicidal ideation, and concomitant MAOI use.
Q6: Why was Dextropropoxyphene withdrawn from the market in many countries?
A: Due to concerns about serious cardiac toxicity (QT prolongation, arrhythmias) and the risk of fatal overdose, even at therapeutic doses.
Q7: What is the mechanism of action of Dextropropoxyphene?
A: It acts as a mu-opioid receptor agonist and also has activity at kappa-opioid receptors and NMDA receptors.
Q8: Can Dextropropoxyphene be used in patients with liver or kidney disease?
A: Historically, dose adjustments were needed for patients with hepatic or renal impairment. Its use is discouraged in these populations, due to altered pharmacokinetics.
Q9: Is Dextropropoxyphene addictive?
A: Yes, like other opioid analgesics, it can be habit-forming and lead to dependence with prolonged use.
