DARVON W/ ASA
Clinical safety rating: caution
Comprehensive 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). |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARVON W/ ASA (DARVON W/ ASA).
| Breastfeeding | Aspirin enters breast milk in low amounts; M/P ratio ~0.1. Propoxyphene M/P ratio ~0.5. Both can accumulate in neonates with repeated dosing. Potential for infant sedation, respiratory depression, and Reye's syndrome. Contraindicated in breastfeeding due to risks. |
| 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. |
■ 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 |
Hypersensitivity to propoxyphene, aspirin, or NSAIDs; severe respiratory depression; acute or severe asthma; GI bleeding; history of peptic ulcer disease; hemophilia; children with viral infections (Reye's syndrome); concurrent MAOIs or alcohol.
| 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. |
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| 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. |
| 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. |