DARVOCET-N 100
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARVOCET-N 100 (DARVOCET-N 100).
Propoxyphene is a weak opioid agonist that binds to mu-opioid receptors in the CNS, altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes centrally, reducing prostaglandin synthesis and providing analgesia.
| Metabolism | Propoxyphene: Hepatic via CYP3A4 and CYP2D6, primarily to norpropoxyphene (active metabolite). Acetaminophen: Hepatic via conjugation (glucuronidation, sulfation) and CYP2E1. |
| Excretion | Propoxyphene: primarily hepatic metabolism to norpropoxyphene, renal excretion of metabolites (20-25% unchanged propoxyphene). Acetaminophen: renal excretion of glucuronide and sulfate conjugates (90-95% total), 2-4% unchanged. |
| Half-life | Propoxyphene: 6-12 hours (prolonged in elderly and hepatic impairment); norpropoxyphene metabolite: 30-36 hours. Acetaminophen: 1.5-3 hours. |
| Protein binding | Propoxyphene: 70-80% bound to albumin and α1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin. |
| Volume of Distribution | Propoxyphene: 16-20 L/kg (extensive tissue distribution). Acetaminophen: 0.9-1.0 L/kg. |
| Bioavailability | Propoxyphene: oral bioavailability ~30% (extensive first-pass metabolism). Acetaminophen: oral bioavailability 70-90%. |
| Onset of Action | Oral: 30-60 minutes. |
| Duration of Action | Propoxyphene: 4-6 hours (analgesic effect); norpropoxyphene accumulation may prolong effects with repeated use. Acetaminophen: 4-6 hours. |
| Molecular Weight | 389.51 |
Darvocet-N 100 contains propoxyphene napsylate 100 mg and acetaminophen 650 mg. For moderate to moderately severe pain, the typical adult dose is 1 tablet orally every 4 hours as needed. Maximum: 6 tablets per day (600 mg propoxyphene napsylate, 3900 mg acetaminophen).
| Dosage form | TABLET |
| Renal impairment | Propoxyphene is primarily renally excreted. For GFR 30-59 mL/min: reduce dose to 1 tablet every 4 hours as needed, maximum 4 tablets per day (400 mg propoxyphene napsylate). For GFR <30 mL/min: avoid use due to accumulation of propoxyphene and its metabolite norpropoxyphene (which has CNS depressant and cardiotoxic effects). |
| Liver impairment | Child-Pugh A: no dose adjustment required. Child-Pugh B: reduce dose to 1 tablet every 6 hours as needed, maximum 4 tablets per day. Child-Pugh C: avoid use due to risk of acute liver injury from acetaminophen and propoxyphene hepatotoxicity. |
| Pediatric use | Safety and efficacy not established in children. Propoxyphene is contraindicated in pediatric patients due to risk of respiratory depression, especially in those less than 12 years old. For adolescents 12 years and older, some sources recommend a dose of 0.5-1 mg/kg of acetaminophen component every 4-6 hours as needed, but propoxyphene is not recommended due to abuse potential and availability of safer alternatives. |
| Geriatric use | Elderly patients (≥65 years) have increased sensitivity to propoxyphene's CNS and respiratory depressant effects. Initiate with 1 tablet every 6 hours as needed, maximum 4 tablets per day. Monitor for sedation, dizziness, and constipation. Propoxyphene should be avoided in the elderly per Beers Criteria due to increased risk of falls and cognitive impairment. |
| 1st trimester | Risk of congenital malformations not established; use only if benefit outweighs risk; avoid in first trimester if possible. |
| 2nd trimester | May cause fetal respiratory depression and dependence; use only if clearly needed. |
| 3rd trimester | May cause neonatal respiratory depression, withdrawal syndrome, and decreased uterine contractions; use only if clearly needed and with careful monitoring. |
Clinical note
Comprehensive clinical and safety monograph for DARVOCET-N 100 (DARVOCET-N 100).
| Placental transfer | Propoxyphene crosses the placenta; reported in cord blood and neonatal serum. |
| Breastfeeding | Propoxyphene is excreted into breast milk in low concentrations. Use with caution in breastfeeding; monitor infant for sedation, respiratory depression, and withdrawal. Consider alternative analgesics if prolonged use. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C for propoxyphene; contraindicated in third trimester due to risk of neonatal opioid withdrawal syndrome (NOWS). First trimester: no clear evidence of major malformations; second trimester: theoretical risk of opioid dependence. Prolonged use may cause neonatal respiratory depression and withdrawal. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and bowel function. Fetal: assess fetal growth and amniotic fluid volume if used long-term. Neonatal: observe for signs of opioid withdrawal (irritability, poor feeding, respiratory distress) if used near term. |
| Fertility Effects | No specific data. Opioid use may disrupt menstrual cycle and reduce fertility. Acetaminophen at therapeutic doses not associated with fertility impairment. |
■ FDA Black Box Warning
Propoxyphene products have been withdrawn from the U.S. market due to risk of fatal overdose, QT prolongation, and cardiac toxicity.
| Serious Effects |
Hypersensitivity to propoxyphene or acetaminophenConcurrent use of alcohol or CNS depressants (including other opioids)Severe respiratory depressionAcute or severe bronchial asthmaParalytic ileusMonoamine oxidase inhibitor (MAOI) use within past 14 days
| Precautions | Risk of overdose, respiratory depression, QT prolongation, Torsades de Pointes, drug dependence, hepatotoxicity (acetaminophen), and interactions with CNS depressants. |
| Food/Dietary | Avoid alcohol. Grapefruit juice may potentiate propoxyphene levels via CYP3A4 inhibition; avoid concurrent intake. High-fat meals may delay absorption but not significantly affect overall exposure. Maintain adequate hydration to prevent constipation. |
| Clinical Pearls | Darvocet-N 100 is a fixed-dose combination of propoxyphene napsylate (100 mg) and acetaminophen (650 mg). Propoxyphene is a weak mu-opioid agonist with a high risk of QT prolongation and cardiac toxicity, especially at supratherapeutic doses. It has been withdrawn in many countries due to fatal arrhythmias. In the US, it was voluntarily withdrawn in 2010. Avoid in patients with renal impairment (accumulation of norpropoxyphene, a toxic metabolite). Monitor for CNS depression and respiratory depression, especially when combined with alcohol or other CNS depressants. Use with caution in elderly or debilitated patients due to increased fall risk. Propoxyphene's analgesic efficacy is only slightly superior to placebo, making it a poor choice for chronic pain. |
| Patient Advice | Do not exceed the prescribed dose; taking more can cause serious heart problems or liver damage. · Avoid alcohol while taking this medication; it increases the risk of severe drowsiness and liver toxicity. · Do not take with other medications containing acetaminophen (e.g., Tylenol) to avoid exceeding the maximum daily dose of 4 grams. · This drug may cause dizziness, drowsiness, or blurred vision; avoid driving or operating heavy machinery until you know how it affects you. · Contact your doctor immediately if you experience fast or irregular heartbeat, fainting, severe nausea/vomiting, or difficulty breathing. · Do not share this medication with others. It is a controlled substance with abuse potential. · Store at room temperature away from moisture and heat. Dispose of unused medication properly (e.g., via drug take-back programs). |
Loading safety data…