DARVOCET-N 50
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARVOCET-N 50 (DARVOCET-N 50).
Propoxyphene is a weak mu-opioid receptor agonist; it also binds to sigma receptors. Acetaminophen inhibits prostaglandin synthesis via COX-1 and COX-2, thereby reducing pain and fever.
| Metabolism | Propoxyphene is metabolized by CYP3A4 to norpropoxyphene (active metabolite). Acetaminophen is metabolized primarily by glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3), with minor oxidation by CYP2E1. |
| Excretion | Acetaminophen: renal (90-100% as metabolites within 24h; 2-4% unchanged). Propoxyphene: renal (25-30% unchanged; metabolites) and biliary/fecal (significant enterohepatic circulation). |
| Half-life | Acetaminophen: 1.5-3 hours (therapeutic); 4-6 hours in overdose due to saturation of metabolism. Propoxyphene: 6-12 hours (parent); norpropoxyphene: 30-36 hours (active metabolite, accumulates with repeated dosing). |
| Protein binding | Acetaminophen: 10-25% (albumin). Propoxyphene: 78-85% (albumin, alpha-1-acid glycoprotein). |
| Volume of Distribution | Acetaminophen: 0.9 L/kg (distributes evenly through body fluids). Propoxyphene: 12-13 L/kg (extensive tissue binding, including lungs and CNS). |
| Bioavailability | Acetaminophen: 60-80% (oral, due to first-pass metabolism). Propoxyphene: 30-70% (oral, extensive first-pass metabolism; interindividual variability). |
| Onset of Action | Oral: 30-60 minutes for analgesia (propoxyphene component); acetaminophen component acts within 30 minutes. |
| Duration of Action | Analgesia: 4-6 hours. Note: Propoxyphene's long half-life leads to accumulation; norpropoxyphene (active metabolite) may prolong duration with repeated dosing. |
| Molecular Weight | 339.47 |
1 tablet (propoxyphene 50 mg, acetaminophen 300 mg) orally every 4 hours as needed for pain, not to exceed 6 tablets per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl < 30 mL/min). For moderate impairment (CrCl 30–59 mL/min), reduce dose interval to every 8 hours and avoid high doses due to propoxyphene accumulation. |
| Liver impairment | Child-Pugh Class A: Use with caution, maximum 4 tablets per day. Child-Pugh Class B: Reduce dose by 50% and monitor. Child-Pugh Class C: Avoid use due to risk of hepatotoxicity and propoxyphene toxicity. |
| Pediatric use | Not recommended for pediatric use due to risk of respiratory depression and abuse potential. |
| Geriatric use | Initiate at lower dose (e.g., one tablet every 6 hours), monitor for CNS depression, and avoid in patients >65 years due to increased fall risk and propoxyphene toxicity. |
| 1st trimester | Avoid; risk of neural tube defects and cardiovascular anomalies with first-trimester exposure to propoxyphene. |
| 2nd trimester | Avoid; potential for fetal respiratory depression and physical dependence. |
| 3rd trimester | Avoid; risk of neonatal opioid withdrawal syndrome and respiratory depression at delivery. |
Clinical note
Comprehensive clinical and safety monograph for DARVOCET-N 50 (DARVOCET-N 50).
| Placental transfer | Propoxyphene and its major metabolite norpropoxyphene cross the placenta; fetal plasma concentrations may approach maternal levels. |
| Breastfeeding | Propoxyphene is excreted into breast milk in small amounts; however, due to risk of neonatal sedation and respiratory depression, breastfeeding is not recommended during therapy. Consider alternative analgesics. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | FDA Pregnancy Category C/D if used long-term or in high doses near term. First trimester: acetaminophen is generally considered low risk; propoxyphene has shown equivocal risk for neural tube defects. Second/third trimester: propoxyphene may cause fetal respiratory depression and neonatal withdrawal with chronic use; acetaminophen is safe in therapeutic doses. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and pain control. Fetal monitoring: non-stress test and biophysical profile if chronic use. Neonatal monitoring: observe for respiratory depression and withdrawal symptoms (irritability, feeding difficulty) after delivery. |
| Fertility Effects | Acetaminophen may inhibit ovulation; propoxyphene may impair female fertility via prolactin elevation. Effects are reversible upon discontinuation. |
■ FDA Black Box Warning
Propoxyphene has been withdrawn from the US market due to risk of fatal cardiac arrhythmias, particularly QTc prolongation and torsade de pointes.
| Serious Effects |
Hypersensitivity to propoxyphene or acetaminophenSuicidal or addiction-prone patientsPatients receiving MAO inhibitors within 14 daysSignificant respiratory depressionAcute or severe bronchial asthmaGI obstruction (e.g., paralytic ileus)
| Precautions | Risk of fatal overdose with alcohol or other CNS depressants; QT prolongation; hepatotoxicity from acetaminophen; respiratory depression; dependence and abuse potential; seizures; withdrawal syndrome. |
| Food/Dietary | Grapefruit and grapefruit juice may increase the levels of propoxyphene and risk of toxicity; avoid concurrent intake. Alcohol can potentiate CNS depression and increase the risk of hepatotoxicity; avoid ethanol consumption. High-fat meals may delay absorption but do not significantly alter overall exposure. |
| Clinical Pearls | DARVOCET-N 50 contains propoxyphene, a weak opioid with efficacy similar to codeine but with a higher risk of QT prolongation and cardiotoxicity, especially at supratherapeutic doses. Propoxyphene is metabolized to norpropoxyphene, which has a long half-life and can accumulate in renal impairment, leading to seizures and cardiac arrhythmias. Due to these risks, propoxyphene was withdrawn from the US market in 2010; however, this monograph is for informational purposes. Avoid use in patients with prolonged QT interval, electrolyte abnormalities, or concurrent use of other QT-prolonging drugs. Monitor for signs of toxicity including confusion, respiratory depression, and cardiac effects. |
| Patient Advice | Do not exceed the prescribed dose as this medication can cause serious heart rhythm problems or seizures. · Avoid alcohol and other central nervous system depressants (e.g., sedatives, tranquilizers) while taking this medication. · This medication may cause dizziness or drowsiness; avoid driving or operating machinery until you know how it affects you. · Do not stop taking this medication abruptly without consulting your doctor, as withdrawal symptoms may occur. · Store this medication out of reach of children and dispose of properly when no longer needed. · Contact your doctor immediately if you experience symptoms of an allergic reaction (rash, hives, difficulty breathing) or signs of heart rhythm problems (fainting, rapid or irregular heartbeat). |
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