Usage
Dextropropoxyphene + Paracetamol is prescribed for the relief of mild to moderate pain. It was commonly used for postoperative pain, acute musculoskeletal pain, and other short-term painful conditions. However, due to safety concerns, particularly cardiotoxicity and overdose risks, many regulatory agencies have withdrawn it from the market. Therefore, its current availability is extremely limited, and it is generally not recommended for use. Where available, it should be used only when alternative analgesics have proven ineffective or intolerable, and it should be used only for short-term treatment of chronic pain of moderate severity.
It is pharmacologically classified as an opioid analgesic, combining a mild opioid (dextropropoxyphene) with a non-opioid analgesic (paracetamol).
The mechanism of action involves dextropropoxyphene binding to mu- and kappa-opioid receptors in the central nervous system, thereby altering pain perception. Paracetamol’s mechanism is not fully understood but involves inhibition of prostaglandin synthesis and other central effects. The combination provides synergistic analgesia.
Alternate Names
Dextropropoxyphene in combination with paracetamol was marketed under various brand names, including:
- Co-proxamol
- Distalgesic
- Di-Gesic
- Capadex
- Paradex
- Darvocet (containing dextropropoxyphene and paracetamol)
- Doloxene (containing dextropropoxyphene alone)
How It Works
Pharmacodynamics: Dextropropoxyphene is a mild opioid agonist acting on mu- and kappa-opioid receptors in the brain and spinal cord, reducing pain signal transmission and perception. Paracetamol has analgesic and antipyretic properties. It inhibits prostaglandin synthesis centrally, and possibly through other central mechanisms. It does not have significant anti-inflammatory activity.
Pharmacokinetics:
- Absorption: Dextropropoxyphene is readily absorbed from the gastrointestinal tract, with the napsylate salt absorbing more slowly than the hydrochloride salt. Paracetamol is rapidly and almost completely absorbed from the GI tract. Food can delay absorption in both cases. Peak plasma levels reached in 1-2 hours.
- Metabolism: Dextropropoxyphene is extensively metabolized in the liver, primarily to nordextropropoxyphene (norpropoxyphene), which has analgesic activity and a long half-life. Paracetamol is metabolized in the liver.
- Elimination: Dextropropoxyphene and its metabolites are excreted primarily in the urine. A small amount of paracetamol is also eliminated in the urine.
- Half-life: 6-12 hours for dextropropoxyphene, 30-36 hours for norpropoxyphene.
Dosage
Due to safety concerns and restricted availability, dosing information is provided for historical context and for regions where it may still be available. It is crucial to consult local guidelines and regulations before prescribing or administering this medication.
Standard Dosage
Adults:
Historically, the standard dose was two tablets (dextropropoxyphene 32.5 mg + paracetamol 325 mg) every four hours as needed. The maximum daily dose was eight tablets.
Children:
Use in children is generally not recommended.
Special Cases:
- Elderly Patients: Dose reduction is recommended due to age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dose reduction is required based on the degree of impairment.
- Patients with Hepatic Dysfunction: Dose reduction is mandatory.
- Patients with Comorbid Conditions: Careful consideration is needed for patients with respiratory problems, cardiovascular disease, and other conditions.
Clinical Use Cases
Dextropropoxyphene + Paracetamol is not recommended for use in these settings due to availability issues and safety concerns. Safer alternative analgesics should be considered.
Dosage Adjustments
Dose adjustments are essential in elderly patients, patients with renal or hepatic impairment, and those with other comorbid conditions.
Side Effects
Common Side Effects:
- Dizziness
- Drowsiness
- Nausea
- Vomiting
- Constipation
- Abdominal pain
- Rash
- Sedation
Rare but Serious Side Effects:
- Cardiotoxicity (arrhythmias, QT prolongation)
- Seizures
- Liver damage (especially with chronic alcohol use or overdose)
- Respiratory depression
- Psychoses
- Suicidal thoughts
Long-Term Effects:
Chronic use can lead to dependence and tolerance. Hepatotoxicity risk increases with prolonged use, especially in patients with pre-existing liver disease or alcohol abuse.
Adverse Drug Reactions (ADR):
Serious ADRs include severe cardiotoxicity, respiratory depression, and hepatotoxicity, requiring immediate medical intervention.
Contraindications
- Hypersensitivity to dextropropoxyphene or paracetamol.
- Severe respiratory depression.
- Acute or severe asthma.
- Bowel obstruction.
- Concurrent use with alcohol or paracetamol-containing products.
- Patients who are suicidal or prone to drug dependence.
- Liver disease, Heart disease, gastric ulcer
Drug Interactions
- Other Opioids: Increased risk of respiratory depression and other opioid-related adverse effects.
- CNS Depressants: Additive sedative effects.
- CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): Increased dextropropoxyphene and norpropoxyphene levels.
- CYP3A4 Inducers (e.g., carbamazepine, rifampicin): Decreased dextropropoxyphene and norpropoxyphene levels.
- Alcohol: Increased risk of hepatotoxicity and other adverse effects.
- Warfarin
- Tricyclic antidepressants (e.g., amitriptyline)
Pregnancy and Breastfeeding
Dextropropoxyphene + Paracetamol should be avoided during pregnancy and breastfeeding due to potential fetal and neonatal risks. Safer alternatives should be used.
Drug Profile Summary
- Mechanism of Action: Opioid and non-opioid analgesic combination.
- Side Effects: Dizziness, drowsiness, nausea, vomiting, constipation, cardiotoxicity, seizures, liver damage, respiratory depression.
- Contraindications: Hypersensitivity, severe respiratory depression, acute asthma, bowel obstruction, concurrent alcohol use, suicidal ideation, drug dependence, liver disease.
- Drug Interactions: Other opioids, CNS depressants, CYP3A4 inhibitors/inducers, alcohol.
- Pregnancy & Breastfeeding: Avoid.
- Dosage: (Historical context only) Adults: Two tablets every four hours, maximum 8 tablets/day. Dose reduction in elderly, renal/hepatic impairment.
- Monitoring Parameters: Respiratory rate, heart rate, blood pressure, liver function tests, ECG (periodically in chronic use).
Popular Combinations
Due to its withdrawal from many markets, dextropropoxyphene is rarely used in combination with other drugs.
Precautions
Pre-existing respiratory, liver, or kidney disease requires careful monitoring. Avoid in patients with a history of substance abuse or suicidal ideation. Caution is advised in the elderly and during pregnancy and breastfeeding. Driving and operating heavy machinery should be avoided due to potential drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dextropropoxyphene + Paracetamol?
A: Refer to the Dosage section. Note that the drug’s availability is limited, and dosage information is provided for historical context and for limited regions where it might still be available.
Q2: What are the major side effects?
A: Dizziness, drowsiness, nausea, vomiting, constipation, and rarely, cardiotoxicity, liver damage and seizures.
Q3: Is Dextropropoxyphene + Paracetamol safe during pregnancy?
A: No, it’s generally avoided during pregnancy due to potential fetal risks.
Q4: Can I drink alcohol while taking this medication?
A: No, alcohol should be strictly avoided as it can exacerbate side effects and increase the risk of liver damage.
Q5: What should I do if I miss a dose?
A: Take the missed dose as soon as remembered unless it is close to the next scheduled dose. Do not double the dose.
Q6: Can I use this medication for long-term pain management?
A: No, it’s typically prescribed for short-term use due to the risk of tolerance, dependence, and other long-term side effects.
Q7: What are the signs of an overdose?
A: Stupor, coma, seizures, respiratory depression, hypotension, and liver damage. Seek immediate medical attention.
Q8: Are there any drug interactions I should be aware of?
A: Yes, it interacts with other opioids, CNS depressants, CYP3A4 inhibitors/inducers, and alcohol. Inform your doctor about all medications you are taking.
Q9: Why is Dextropropoxyphene + Paracetamol no longer widely available?
A: It has been withdrawn from many markets due to safety concerns, including cardiotoxicity and overdose risks, along with questions regarding its effectiveness.
