DARVON COMPOUND
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | Propoxyphene: 339.47 Da (hydrochloride); Aspirin: 180.16 Da (note: Darvon Compound contains propoxyphene and aspirin, so weight is for individual components). |
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 | Avoid due to risk of teratogenicity; aspirin component associated with neural tube defects and cardiovascular malformations. |
| 2nd trimester | Avoid; aspirin may cause premature closure of ductus arteriosus and oligohydramnios; propoxyphene may cause neonatal withdrawal. |
| 3rd trimester | Avoid; aspirin increases risk of maternal and fetal bleeding, premature closure of ductus arteriosus, and delayed labor; propoxyphene may cause neonatal respiratory depression and withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for DARVON COMPOUND (DARVON COMPOUND).
| Placental transfer | Both propoxyphene and aspirin cross the placenta; propoxyphene achieves cord blood levels 50-100% of maternal levels; aspirin crosses readily with fetal levels exceeding maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; potential for infant sedation or respiratory depression; avoid use or monitor infant closely; safer alternatives preferred. |
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
■ 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 or aspirinSevere asthmaBleeding disorders (e.g., hemophilia)Active peptic ulcer diseaseSevere hepatic or renal impairmentConcurrent use of MAOIs or within 14 days of stoppingChildren with viral infections (Reye's syndrome risk with aspirin)Third trimester of pregnancy
| 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. |
| Food/Dietary | Avoid alcohol, as it increases propoxyphene CNS depression and hepatotoxicity. Limit caffeine-containing foods/beverages due to additive effects with caffeine component. Aspirin absorption is delayed by food; take on empty stomach for faster relief, but with food if GI upset occurs. |
| Clinical Pearls | Darvon Compound contains propoxyphene, aspirin, and caffeine. Due to propoxyphene's risk of QT prolongation and fatal arrhythmias, especially at supratherapeutic doses, it was withdrawn from the US market in 2010. Use is contraindicated in patients with prolonged QT interval, electrolyte disturbances, or on other QT-prolonging drugs. Aspirin component requires caution in bleeding disorders, peptic ulcer disease, and children with viral illness due to Reye's syndrome risk. Caffeine may exacerbate anxiety or insomnia. |
| Patient Advice | Do not exceed recommended dose; propoxyphene overdose can cause life-threatening heart rhythm problems. · Avoid alcohol and other CNS depressants while taking this medication. · If you have a history of heart disease, low potassium/magnesium, or take other medications, inform your doctor. · Aspirin may increase bleeding risk; avoid if you have stomach ulcers or take blood thinners. · Discontinue and seek medical attention if you experience fainting, rapid heartbeat, or signs of allergic reaction. · Keep out of reach of children; accidental overdose can be fatal. |
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