DARVOCET-N 100
Clinical safety rating: caution
Comprehensive 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. |
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 |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARVOCET-N 100 (DARVOCET-N 100).
| Breastfeeding | Propoxyphene and acetaminophen are excreted in breast milk. M/P ratio for propoxyphene is approximately 0.5. Concentrations in milk are low; risk of infant sedation is minimal with short-term use. Caution with prolonged use or high doses. Monitor infant for drowsiness and feeding difficulties. |
| 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. |
■ 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 acetaminophen, significant respiratory depression, acute or severe bronchial asthma, suspected gastrointestinal obstruction, concurrent use of MAOIs or linezolid, and patients with known QT prolongation or cardiac arrhythmias.
| Precautions | Risk of overdose, respiratory depression, QT prolongation, Torsades de Pointes, drug dependence, hepatotoxicity (acetaminophen), and interactions with CNS depressants. |
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| 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. |
| 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. |