DARVON-N W/ ASA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DARVON-N W/ ASA (DARVON-N W/ ASA).
Propoxyphene is a weak opioid agonist that binds to mu-opioid receptors in the CNS, altering pain perception. Aspirin inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis, which mediates pain, fever, and inflammation.
| Metabolism | Propoxyphene is metabolized via CYP3A4 to norpropoxyphene (active metabolite). Aspirin is hydrolyzed to salicylic acid and conjugated with glycine (salicyluric acid) and glucuronic acid. |
| Excretion | Renal: propoxyphene and its metabolites (norpropoxyphene) are primarily eliminated via kidneys, with ~20-25% excreted unchanged; fecal: minor; biliary: some enterohepatic recirculation occurs, but exact % are not well quantified for the combination product. Aspirin is hydrolyzed to salicylate, which is excreted renally (75% as salicyluric acid, 10% as salicylic acid, 10% as glucuronide conjugates, and minor amounts as gentisic acid). |
| Half-life | Propoxyphene: terminal elimination half-life is 6-12 hours in adults with normal renal function; norpropoxyphene has a longer half-life (30-36 hours). Aspirin (as salicylate): half-life is dose-dependent, ranging from 2-3 hours at low doses to 15-30 hours at anti-inflammatory doses (300-600 mg in Darvon-N W/ASA). |
| Protein binding | Propoxyphene: ~80% bound to albumin; norpropoxyphene: ~90% bound. Aspirin: 50-80% bound to albumin (dose-dependent); salicylate: 50-90% bound. |
| Volume of Distribution | Propoxyphene: 10-16 L/kg (large Vd indicating extensive tissue distribution); norpropoxyphene: similar. Aspirin: 0.1-0.2 L/kg (limited distribution as salicylate is highly protein-bound). |
| Bioavailability | Oral propoxyphene: 30-70% due to first-pass metabolism (higher for propoxyphene napsylate than hydrochloride). Aspirin: 50-75% (but rapidly hydrolyzed to salicylate, which has near-complete bioavailability after oral administration). |
| Onset of Action | Oral: propoxyphene analgesia begins within 15-30 minutes; aspirin (as analgesic/antipyretic) onset at 30-60 minutes. |
| Duration of Action | Propoxyphene: 4-6 hours; aspirin: analgesic/antipyretic effect lasts 3-4 hours (dose-dependent up to 6 hours for antiplatelet effect). |
1-2 capsules (propoxyphene napsylate 100 mg / aspirin 325 mg per capsule) orally every 4 hours as needed for pain; maximum 6 capsules per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: avoid use; GFR <30 mL/min: contraindicated due to propoxyphene accumulation. Aspirin component may further impair renal function. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% or extend interval; Class C: contraindicated due to increased propoxyphene toxicity and bleeding risk from aspirin. |
| Pediatric use | Not recommended for pediatric use due to risk of Reye's syndrome (aspirin) and propoxyphene toxicity. |
| Geriatric use | Initiate with half the adult dose (maximum 1 capsule every 6 hours) due to increased sensitivity, reduced clearance, and higher risk of CNS and GI adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARVON-N W/ ASA (DARVON-N W/ ASA).
| Breastfeeding | Propoxyphene excreted into breast milk; M/P ratio approximate 0.5; ASA excreted in low amounts. Potential for neonatal opioid effects (respiratory depression, sedation) and Reye's syndrome with ASA. Contraindicated in breastfeeding due to risks; alternative agents recommended. |
| Teratogenic Risk | First trimester: ASA associated with neural tube defects, gastroschisis; propoxyphene limited data, possible cardiac defects. Second trimester: ASA may reduce amniotic fluid; propoxyphene risk not established. Third trimester: ASA increases risk of premature ductus arteriosus closure, oligohydramnios, neonatal hemorrhage; propoxyphene may cause neonatal respiratory depression, withdrawal. Overall risk considered moderate; avoid in third trimester. |
■ FDA Black Box Warning
Propoxyphene has been withdrawn from the US market due to risk of fatal cardiac toxicity (QT prolongation, Torsades de Pointes). FDA boxed warning prior to withdrawal included risk of respiratory depression, abuse potential, and fatal overdose.
| Serious Effects |
Hypersensitivity to propoxyphene or aspirin, significant respiratory depression, acute or severe bronchial asthma, known QT prolongation, children with viral illness (Reye's syndrome risk), third trimester of pregnancy (aspirin), history of aspirin-induced asthma or nasal polyps.
| Precautions | Risk of respiratory depression, QT prolongation, cardiac arrhythmias, abuse potential, hepatotoxicity (overdose), aspirin hypersensitivity, bleeding risk (aspirin), Reye's syndrome (in children with viral illness). |
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| Fetal Monitoring | Maternal: renal function, hepatic function, bleeding time, opioid adverse effects. Fetal: ultrasound for amniotic fluid index, ductus arteriosus patency (third trimester), growth parameters. Neonatal: observe for respiratory depression, withdrawal symptoms, and bleeding. |
| Fertility Effects | ASA may inhibit prostaglandin synthesis affecting ovulation and implantation; propoxyphene may cause menstrual irregularities and reduce fertility via opioid-mediated endocrine disruption. Reversible upon discontinuation. |