DARVOCET A500
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARVOCET A500 (DARVOCET A500).
Combination analgesic: acetaminophen inhibits cyclooxygenase (COX) and modulates endocannabinoid system; propoxyphene is a mu-opioid receptor agonist.
| Metabolism | Propoxyphene: hepatic via CYP3A4 and CYP2D6; active metabolite norpropoxyphene. Acetaminophen: hepatic via conjugation (glucuronidation, sulfation) and CYP2E1. |
| Excretion | Propoxyphene: ~20-25% renal as unchanged drug, ~35% as norpropoxyphene, ~20% biliary/fecal. Acetaminophen: ~2-4% renal unchanged, ~85% as glucuronide and sulfate conjugates, ~5% as cysteine and mercapturate conjugates. |
| Half-life | Propoxyphene: 6-12 hours (terminal, prolonged in elderly, hepatic impairment, or overdose). Acetaminophen: 2-3 hours (terminal, prolonged in hepatic impairment or overdose). |
| Protein binding | Propoxyphene: ~78% bound to albumin. Acetaminophen: 10-25% bound (minimal). |
| Volume of Distribution | Propoxyphene: 16 L/kg (extensive tissue distribution). Acetaminophen: 0.9 L/kg. |
| Bioavailability | Propoxyphene: 30-70% (first-pass metabolism). Acetaminophen: ~88% (oral). |
| Onset of Action | Oral: 30-60 minutes (both components). |
| Duration of Action | Analgesia: 4-6 hours (propoxyphene effect). Acetaminophen: 4-6 hours. |
| Molecular Weight | 339.47 |
One tablet (500 mg acetaminophen, 100 mg propoxyphene napsylate) orally every 4 hours as needed for pain; maximum 6 tablets per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). For GFR 30-50 mL/min: reduce dose to 1 tablet every 6 hours. Monitor for propoxyphene accumulation. |
| Liver impairment | Avoid use in Child-Pugh class C (severe hepatic impairment). In Child-Pugh class A or B: use with caution, reduce dose by 50% (e.g., 1 tablet every 6-8 hours), and avoid chronic use due to acetaminophen toxicity risk. |
| Pediatric use | Not recommended for pediatric use due to safety concerns (propoxyphene associated with respiratory depression in children). For adolescents >12 years: 1 tablet every 4 hours as needed; maximum 6 tablets/day. |
| Geriatric use | Start at 1 tablet every 6-8 hours; avoid exceeding 4 tablets/day. Monitor for CNS depression, constipation, and falls. Consider decreased hepatic/renal function and increased sensitivity. |
| 1st trimester | Avoid; risk of neural tube defects and other congenital anomalies due to propoxyphene component. |
| 2nd trimester | Avoid; potential fetal harm, including physical dependence and withdrawal symptoms. |
| 3rd trimester | Avoid; risk of neonatal respiratory depression, withdrawal, and prolonged labor. |
Clinical note
Comprehensive clinical and safety monograph for DARVOCET A500 (DARVOCET A500).
| Placental transfer | Both propoxyphene and acetaminophen cross the placenta; propoxyphene has known fetal effects. |
| Breastfeeding | Propoxyphene and acetaminophen are excreted into breast milk. Due to the risk of neonatal respiratory depression and withdrawal, use is not recommended. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | First trimester: Propoxyphene crosses placenta, limited data; possible association with neural tube defects. Second trimester: Avoid; risk of fetal respiratory depression. Third trimester: Avoid; neonatal withdrawal syndrome (tremors, hypertonia) and respiratory depression at delivery. |
| Fetal Monitoring | Monitor maternal respiratory rate, CNS depression, bowel function. Fetal: ultrasound for growth restriction, nonstress test if chronic use. Neonatal: observe for withdrawal symptoms (Naloxone may reverse propoxyphene effects). |
| Fertility Effects | No known adverse effects on human fertility reported. Animal studies show no impairment. Acetaminophen may slightly reduce female fertility in high doses (unlikely at therapeutic dosing). |
■ FDA Black Box Warning
Propoxyphene is associated with fatal respiratory depression, abuse potential, and risk of overdose; contraindicated in patients with suicidal ideation or addiction.
| Serious Effects |
Hypersensitivity to propoxyphene, acetaminophen, or any componentSuicidal tendencies or addiction-prone patients (propoxyphene)Use with alcohol or other CNS depressantsSevere respiratory depressionAcute or severe bronchial asthmaParalytic ileus
| Precautions | Risk of respiratory depression, abuse and dependence, cardiac toxicity (QT prolongation, arrhythmias), acetaminophen hepatotoxicity, increased seizure risk in patients with CNS depression, interaction with CNS depressants. |
| Food/Dietary | Take with food to reduce gastrointestinal upset. Avoid grapefruit juice as it may increase propoxyphene absorption. Avoid alcohol entirely due to increased hepatotoxicity and CNS depression. High-fat meals may delay absorption of propoxyphene, but no specific restrictions. |
| Clinical Pearls | Darvocet A500 contains propoxyphene and acetaminophen. Propoxyphene is a weak mu-opioid agonist with high interindividual variability in metabolism. Avoid in patients with creatinine clearance <30 mL/min due to accumulation of norpropoxyphene, which can cause cardiac toxicity (QT prolongation, risk of fatal arrhythmias). Do not exceed 600 mg propoxyphene base (or equivalent) per day. Monitor liver function due to acetaminophen, especially in patients with hepatic impairment or chronic alcohol use. Use with caution in elderly due to increased fall risk and respiratory depression. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not drink alcohol while taking this medication; it increases risk of liver damage and sedation. · Avoid driving or operating heavy machinery until you know how this drug affects you. · Do not take other medications containing acetaminophen to avoid exceeding the maximum daily dose (3000 mg). · Contact your doctor immediately if you experience irregular heartbeat, fainting, or severe dizziness. · Store at room temperature, away from moisture and heat, and out of reach of children. · Do not share this medication with others; it can cause serious harm or death. · If you miss a dose, skip it and resume your regular schedule; do not double the dose. |
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