DARVOCET
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARVOCET (DARVOCET).
Darvocet is a combination of propoxyphene, a mu-opioid receptor agonist that alters perception of and response to pain, and acetaminophen, which inhibits COX enzymes and modulates descending serotonergic pathways.
| Metabolism | Propoxyphene: extensively metabolized via CYP3A4 to norpropoxyphene (active metabolite); Acetaminophen: metabolized primarily via glucuronidation and sulfation, with minor CYP2E1 oxidation. |
| Excretion | Propoxyphene: primarily hepatic metabolism to norpropoxyphene, renal excretion of metabolites (<1% unchanged). Acetaminophen: renal excretion of conjugates (85-90%) and unchanged drug (2-4%). |
| Half-life | Propoxyphene: 6-12 hours (parent), 30-36 hours (norpropoxyphene). Acetaminophen: 1-4 hours (therapeutic doses). Accumulation of norpropoxyphene occurs with repeated dosing. |
| Protein binding | Propoxyphene: 80% bound to albumin. Acetaminophen: 10-25% bound to albumin. |
| Volume of Distribution | Propoxyphene: 10-16 L/kg (large due to lipophilicity). Acetaminophen: 0.9-1.0 L/kg (distributes evenly in body fluids). |
| Bioavailability | Propoxyphene: oral bioavailability ~40% due to first-pass metabolism. Acetaminophen: oral bioavailability 80-90%. |
| Onset of Action | Oral: propoxyphene peak effect at 1-2 hours; acetaminophen peak effect at 30-60 minutes. |
| Duration of Action | Propoxyphene: 4-6 hours (analgesia). Acetaminophen: 4-6 hours (antipyretic/analgesic). Norpropoxyphene prolongs potential toxicity. |
| Molecular Weight | 339.48 |
| Brand Substitutes | Caybutyl 650 mg/65 mg Tablet, Corbutyl 650mg/65mg Tablet, Kortyl 650mg/65mg Tablet, Paraphen 650mg/65mg Tablet |
1 tablet (propoxyphene 100 mg / acetaminophen 650 mg) orally every 4 hours as needed for pain; maximum 6 tablets per day.
| Dosage form | TABLET |
| Renal impairment | For creatinine clearance <50 mL/min: avoid use; propoxyphene accumulates causing CNS and cardiac toxicity. For 50–80 mL/min: reduce frequency to every 6 hours. Not recommended in ESRD or dialysis. |
| Liver impairment | Child-Pugh Class A: cautious use, reduce dose by 50% and monitor. Child-Pugh Class B or C: contraindicated due to risk of hepatotoxicity from acetaminophen and altered propoxyphene metabolism. |
| Pediatric use | Not recommended for pediatric use due to risk of serious adverse effects; safety and efficacy not established. |
| Geriatric use | Start with 1 tablet (100/650 mg) every 6 hours; maximum 4 tablets per day. Avoid in patients with renal impairment or multiple comorbidities. Increased risk of CNS depression and falls. |
| 1st trimester | Avoid use due to risk of teratogenicity; acetaminophen component considered safe but propoxyphene associated with neonatal withdrawal and possible malformations. |
| 2nd trimester | Avoid use; no clear evidence of safety during organogenesis; propoxyphene may cause fetal dependence. |
| 3rd trimester | Avoid use near term; propoxyphene can cause neonatal respiratory depression and withdrawal syndrome. |
Clinical note
Comprehensive clinical and safety monograph for DARVOCET (DARVOCET).
| Placental transfer | Both acetaminophen and propoxyphene cross the placenta. Propoxyphene achieves fetal/maternal ratios of 0.8-0.9, indicating significant transfer. |
| Breastfeeding | Propoxyphene is excreted into breast milk in low concentrations; however, due to the risk of neonatal respiratory depression and sedation, breastfeeding is generally not recommended. Consider alternative analgesics with better safety profiles. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Pregnancy Category C. First trimester: No evidence of structural malformations from acetaminophen; propoxyphene has not been associated with increased risk of major birth defects. Second and third trimesters: Chronic use may lead to neonatal withdrawal syndrome (irritability, hypertonia, tremors) and respiratory depression. High-dose or prolonged use near term associated with neonatal respiratory depression. |
| Fetal Monitoring | Monitor maternal liver function tests and renal function in prolonged use. Fetal: Nonstress test and biophysical profile if used chronically in third trimester. Neonatal: Observe for signs of withdrawal if used near term. |
| Fertility Effects | No adequate studies on fertility. Propoxyphene may impair ovulation and sperm motility based on animal data; clinical significance unknown. |
■ FDA Black Box Warning
Propoxyphene has been withdrawn from the US market due to risk of fatal overdose; Darvocet is no longer available in the US.
| Serious Effects |
Hypersensitivity to propoxyphene or acetaminophenKnown propoxyphene abuse or dependenceSignificant respiratory depressionAcute or severe bronchial asthmaConcurrent use of MAO inhibitors or within 14 daysSuicidal ideation or actions
| Precautions | Respiratory depression, QT prolongation (propoxyphene), hepatotoxicity (acetaminophen at high doses), abuse potential, interaction with alcohol and CNS depressants. |
| Food/Dietary | Avoid alcohol. No specific food interactions, but take with food if gastrointestinal upset occurs. Maintain adequate hydration and fiber intake to prevent constipation. |
| Clinical Pearls | Darvocet contains propoxyphene, a weak opioid with potential for cardiac toxicity (QT prolongation) at high doses. Avoid in patients with history of substance abuse, suicidal ideation, or concurrent use of CNS depressants. Efficacy similar to aspirin, but with higher risk of adverse effects; consider safer alternatives. Monitor for respiratory depression in elderly or debilitated patients. |
| Patient Advice | Take exactly as prescribed; do not take more than recommended dose. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines) as they increase risk of serious side effects. · Do not drive or operate heavy machinery until you know how this medication affects you. · Do not stop abruptly; withdrawal may occur. Taper under medical supervision. · Report severe constipation, difficulty breathing, or signs of allergic reaction. · Store securely away from children and others; dispose properly when no longer needed. |
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