DARVON W/ ASA
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARVON W/ ASA (DARVON W/ ASA).
Combination analgesic: propoxyphene is a weak opioid agonist binding to mu-opioid receptors, inhibiting ascending pain pathways; aspirin irreversibly inhibits cyclooxygenase-1 and -2, reducing prostaglandin synthesis.
| Metabolism | Propoxyphene undergoes hepatic metabolism via N-demethylation to norpropoxyphene (active metabolite); both are primarily excreted renally. Aspirin is rapidly hydrolyzed to salicylate, which is metabolized by conjugation and oxidation, with renal excretion. |
| Excretion | Renal elimination of propoxyphene and its metabolites accounts for ~70% of a dose, with ~20% excreted unchanged in urine; biliary/fecal elimination accounts for ~10%; aspirin is renally excreted as salicylate and its conjugates. |
| Half-life | Propoxyphene terminal half-life is 6–12 hours (mean 8 h) in healthy adults; prolonged in hepatic impairment or elderly due to reduced metabolism. Aspirin half-life is 15–20 minutes due to rapid hydrolysis to salicylate. |
| Protein binding | Propoxyphene is 70–80% bound to albumin; aspirin is 50–80% bound to albumin (dose-dependent due to saturable binding). |
| Volume of Distribution | Propoxyphene Vd is 6–10 L/kg, indicating extensive tissue distribution; aspirin Vd is 0.15–0.2 L/kg, primarily in plasma and extracellular fluid. |
| Bioavailability | Propoxyphene: 30–70% oral bioavailability due to first-pass metabolism; aspirin: 50–70% oral bioavailability (first-pass hydrolysis to salicylate). |
| Onset of Action | Oral: Propoxyphene onset of analgesia is 15–30 minutes; aspirin onset is 30–60 minutes. |
| Duration of Action | Oral: Propoxyphene analgesic duration is 4–6 hours; aspirin antipyretic/analgesic effect lasts 3–4 hours (higher doses extend to 6 h). |
| Molecular Weight | Propoxyphene napsylate: 565.7 Da; Aspirin: 180.16 Da |
1 capsule (propoxyphene HCl 65 mg / aspirin 650 mg) orally every 4 hours as needed for pain, not to exceed 6 capsules per day.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in severe renal impairment (eGFR <30 mL/min/1.73m²). For moderate impairment (eGFR 30-59), reduce dose to 1 capsule every 6 hours. No adjustment needed for mild impairment (eGFR ≥60). |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class B, maximum 2 capsules per day. For Child-Pugh class A, no adjustment required but monitor closely. |
| Pediatric use | Not recommended for children under 12 years. For children 12-18 years: 1 capsule (propoxyphene 65 mg/aspirin 650 mg) every 4 hours as needed, maximum 6 capsules/day. Weight-based dosing not established due to fixed combination. |
| Geriatric use | Initiate with 1 capsule every 6 hours. Maximum 4 capsules per day due to increased sensitivity and risk of CNS depression and renal impairment. Avoid in patients >75 years or those with frailty. |
| 1st trimester | Avoid; propoxyphene associated with neural tube defects and aspirin linked to gastroschisis. |
| 2nd trimester | Caution; avoid prolonged use. Aspirin may affect fetal renal function and closure of ductus arteriosus. |
| 3rd trimester | Contraindicated; aspirin can cause premature closure of ductus arteriosus and oligohydramnios; propoxyphene can cause neonatal withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for DARVON W/ ASA (DARVON W/ ASA).
| Placental transfer | Both propoxyphene and aspirin cross the placenta. Propoxyphene achieves fetal plasma levels similar to maternal. Aspirin is extensively transferred. |
| Breastfeeding | Propoxyphene and aspirin are excreted into breast milk. Aspirin may cause Reye's syndrome in infants; avoid or use lowest effective dose for short duration. Monitor infant for sedation and bleeding. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Aspirin component associated with increased risk of neural tube defects and gastroschisis. Propoxyphene not associated with major malformations but data limited. Second trimester: Aspirin risk increases for fetal intracranial hemorrhage with chronic use. Third trimester: Aspirin may cause premature closure of ductus arteriosus, oligohydramnios, and increased perinatal hemorrhage. Propoxyphene may cause neonatal withdrawal syndrome. |
| Fetal Monitoring | Maternal: Bleeding time, platelet count, liver function tests, renal function, signs of bleeding, respiratory depression, and withdrawal symptoms. Fetal: Ultrasound for ductus arteriosus patency, amniotic fluid volume, growth scans, and fetal heart rate monitoring, especially near term. |
| Fertility Effects | Aspirin may inhibit prostaglandin synthesis, potentially impairing ovulation and luteal function. Propoxyphene may affect hypothalamic-pituitary-gonadal axis, but evidence limited. Both may reduce fertility in women; reversible upon discontinuation. |
■ FDA Black Box Warning
Propoxyphene is associated with a risk of fatal respiratory depression, especially in overdose or when combined with CNS depressants. Use with caution in elderly, debilitated, or patients with respiratory compromise.
| Serious Effects |
Known hypersensitivity to propoxyphene, aspirin, or NSAIDsSevere asthma with nasal polyps (aspirin-sensitive asthma)Active peptic ulcer disease or gastrointestinal bleedingHemorrhagic disorders (e.g., hemophilia, von Willebrand disease)Children <12 years with viral illness (Reye's syndrome risk)Third trimester pregnancy (due to aspirin component)Concurrent use with alcohol or other CNS depressants (increased risk of respiratory depression)History of opioid addiction or abuse
| Precautions | Risk of respiratory depression; hepatotoxicity with chronic high doses; GI bleeding, ulceration, and perforation with aspirin; renal toxicity; hypersensitivity reactions; use in elderly, renal/hepatic impairment, or history of alcohol abuse. |
| Food/Dietary | Avoid alcohol. Aspirin component may cause gastrointestinal irritation; take with food or milk to reduce stomach upset. Avoid foods high in tyramine (e.g., aged cheese, processed meats) as propoxyphene may have weak MAOI activity? Not established but caution advised. |
| Clinical Pearls | Darvon with ASA contains propoxyphene and aspirin. Propoxyphene has been withdrawn from the US market due to cardiotoxicity (QT prolongation, risk of fatal arrhythmias). Use is not recommended; consider alternatives. Aspirin component increases bleeding risk, especially with concurrent anticoagulants. Avoid in children with viral illness due to Reye's syndrome risk. |
| Patient Advice | Do not take more than prescribed as overdose can cause serious heart problems or death. · Avoid alcohol while taking this medication as it increases risk of liver damage and bleeding. · Aspirin may increase risk of bleeding; report unusual bruising or bleeding to your doctor. · If you have asthma, nasal polyps, or allergies, aspirin may cause severe allergic reactions. · Do not use in children or teenagers with chickenpox or flu-like symptoms due to risk of Reye's syndrome. · This medicine may cause drowsiness or dizziness; avoid driving until you know how it affects you. |
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