DARVON COMPOUND-65
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DARVON COMPOUND-65 (DARVON COMPOUND-65).
DARVON COMPOUND-65 contains propoxyphene, a centrally acting opioid agonist with analgesic effects primarily mediated through mu-opioid receptors. Aspirin inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis. Caffeine is a CNS stimulant with additive analgesic effects.
| Metabolism | Propoxyphene undergoes extensive first-pass metabolism via CYP3A4 and CYP2D6 to norpropoxyphene. Aspirin is hydrolyzed to salicylic acid and conjugated in the liver. Caffeine is metabolized by CYP1A2. |
| Excretion | Renal: ~90% as propoxyphene and metabolites (nordextropropoxyphene); biliary/fecal: ~10% |
| Half-life | Propoxyphene: 6-12 hours (mean 8 h); nordextropropoxyphene: 22-30 hours (accumulates with repeated dosing; risk of toxicity) |
| Protein binding | 78-85% (primarily albumin) |
| Volume of Distribution | 12-16 L/kg (extensive tissue distribution; high lipid solubility) |
| Bioavailability | Oral: ~40% (extensive first-pass metabolism) |
| Onset of Action | Oral: 15-60 minutes |
| Duration of Action | 4-6 hours (analgesia); may be prolonged with hepatic impairment or in elderly |
1 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 if CrCl <10 mL/min. For CrCl 10-50 mL/min: reduce dose to 1 capsule every 6 hours; maximum 4 capsules per day. For CrCl >50 mL/min: no adjustment needed. |
| Liver impairment | Contraindicated in Child-Pugh class C. Child-Pugh A or B: reduce dose to 1 capsule every 6 hours; maximum 4 capsules per day. Avoid in severe hepatic impairment. |
| Pediatric use | Not recommended for patients under 18 years due to risk of Reye's syndrome from aspirin content. |
| Geriatric use | Start with 1 capsule every 6 hours; monitor for sedation, dizziness, and constipation. Avoid in patients with renal impairment (CrCl <50 mL/min). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARVON COMPOUND-65 (DARVON COMPOUND-65).
| Breastfeeding | Excreted into breast milk in low concentrations. M/P ratio not established. American Academy of Pediatrics considers compatible with breastfeeding; monitor infant for drowsiness and feeding difficulties. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Risk of neural tube defects based on case reports; avoid if possible. Second and third trimesters: Chronic use may lead to neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth; use only if benefit outweighs risk. |
■ FDA Black Box Warning
Propoxyphene has been withdrawn from the US market due to risk of fatal overdose, QT prolongation, and serious adverse effects. Avoid use with alcohol or other CNS depressants.
| Serious Effects |
Hypersensitivity to any component; severe asthma; bleeding disorders; peptic ulcer disease; concomitant use with MAOIs; pregnancy (especially third trimester); history of substance abuse; patients at risk for prolonged QT.
| Precautions | Risk of respiratory depression, drug dependence, QT prolongation, and seizures. Avoid in patients with severe hepatic or renal impairment. Do not exceed recommended dose. |
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| Fetal Monitoring |
| Monitor maternal respiratory rate, sedation level, and bowel function. Fetal: Ultrasound for growth restriction if prolonged use; assess for NOWS signs in neonates (e.g., high-pitched cry, tremors). |
| Fertility Effects | May impair female fertility via disruption of menstrual cycle and hypothalamic-pituitary-gonadal axis. Tolerance and physical dependence may occur with chronic use. |