DARVON COMPOUND
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DARVON COMPOUND (DARVON COMPOUND).
Darvon Compound is a combination of propoxyphene, aspirin, and caffeine. Propoxyphene is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Aspirin inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing anti-inflammatory and analgesic effects. Caffeine is a CNS stimulant that may enhance analgesia through adenosine receptor antagonism.
| Metabolism | Propoxyphene: Hepatic via CYP3A4 to norpropoxyphene (active metabolite); Aspirin: Hydrolyzed by esterases to salicylate, further conjugated in the liver; Caffeine: Hepatic via CYP1A2 to paraxanthine, theobromine, and theophylline. |
| Excretion | Renal: ~70% as unchanged drug and glucuronide conjugates (propoxyphene and acetaminophen). Fecal: <10% as unchanged and metabolites. Biliary: minor route for propoxyphene conjugates. |
| Half-life | Propoxyphene: 6-12 hours (terminal, prolonged in overdose due to enterohepatic recirculation). Acetaminophen: 2-3 hours (terminal). Clinical context: accumulation in elderly, hepatic impairment. |
| Protein binding | Propoxyphene: ~80% (albumin). Acetaminophen: 10-25% (albumin; lower at toxic concentrations). |
| Volume of Distribution | Propoxyphene: 0.9-1.2 L/kg (wide distribution, high tissue binding). Acetaminophen: 0.8-1.0 L/kg (uniform distribution). |
| Bioavailability | Propoxyphene: 30-70% (first-pass metabolism, dose-dependent; higher with food). Acetaminophen: 60-90% (oral, variable first-pass; >95% for rectal? Not applicable here). |
| Onset of Action | Oral: 30-60 minutes for analgesic effect (propoxyphene); acetaminophen onset similar. |
| Duration of Action | Analgesic: 4-6 hours (propoxyphene; shorter at low doses); acetaminophen 4-6 hours. Note: Duration limited by liver metabolism; toxic metabolites accumulate in overdose. |
One capsule (propoxyphene HCl 65 mg, aspirin 389 mg, caffeine 32.4 mg) orally every 4 hours as needed for pain. Maximum 6 capsules per day.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in severe renal impairment (eGFR <30 mL/min). For moderate impairment (eGFR 30-59 mL/min): reduce dose to 1 capsule every 6 hours; maximum 4 capsules/day. Avoid in ESRD. |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class A or B: reduce dose by 50% (max 3 capsules/day) and monitor for sedation and respiratory depression. |
| Pediatric use | Not recommended for pediatric patients due to risk of propoxyphene cardiotoxicity and aspirin-associated Reye's syndrome in viral illness. |
| Geriatric use | Initiate with 1 capsule every 6 hours; maximum 4 capsules/day. Avoid in patients >80 years due to increased risk of CNS depression, falls, and bleeding from aspirin. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARVON COMPOUND (DARVON COMPOUND).
| Breastfeeding | Propoxyphene excreted in breast milk in low concentrations (M/P ratio ~0.2); may cause sedation or respiratory depression in infants; avoid use in breastfeeding due to potential CNS effects. Acetaminophen M/P ratio ~0.9-1.0, considered compatible at recommended doses. |
| Teratogenic Risk | Darvon Compound contains propoxyphene and acetaminophen. Propoxyphene: FDA pregnancy category C; risk of respiratory depression in neonates if used near term; increased risk of premature labor and low birth weight with chronic use; possible congenital malformations (cleft palate, cardiac defects) in first trimester based on animal studies. Acetaminophen: generally considered low risk in pregnancy; no consistent evidence of teratogenicity. Avoid in third trimester due to risk of neonatal withdrawal syndrome. |
■ FDA Black Box Warning
Propoxyphene has been withdrawn from the U.S. market due to risk of fatal overdose (QT prolongation and cardiac arrhythmias). Use is contraindicated in patients at risk for QT prolongation. Avoid concurrent use with CYP3A4 inhibitors.
| Serious Effects |
Hypersensitivity to propoxyphene, aspirin, caffeine, or NSAIDs; patients with QT interval prolongation or on QT-prolonging drugs; concurrent use of CYP3A4 inhibitors (e.g., ketoconazole, ritonavir); children with viral illness (Reye's syndrome risk); severe renal or hepatic impairment; asthma or nasal polyps (aspirin sensitivity); active peptic ulcer disease or bleeding disorders.
| Precautions | Risk of fatal overdose (QT prolongation, cardiac arrest); respiratory depression; drug dependence and abuse; caution in renal or hepatic impairment; avoid in patients with bleeding disorders (aspirin); Reye's syndrome risk in children with viral illness; caffeine may worsen anxiety or insomnia. |
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| Fetal Monitoring | Monitor for maternal respiratory depression, sedation, constipation, and acetaminophen hepatotoxicity. Fetal: Fetal heart rate monitoring if used near term; neonatal assessment for withdrawal symptoms (irritability, hypertonia, tremors) after chronic maternal use. Liver function tests due to acetaminophen component. |
| Fertility Effects | Propoxyphene may impair fertility by altering hormone levels or causing anovulation. Acetaminophen may reduce fertility by affecting prostaglandin synthesis necessary for ovulation; limited data in humans. |