DARVON
Clinical safety rating
cautionComprehensive clinical and safety monograph for DARVON (DARVON).
Propoxyphene is a mu-opioid receptor agonist that inhibits ascending pain pathways by binding to opioid receptors in the CNS, altering pain perception. It also has weak local anesthetic effects.
| Metabolism | Primarily hepatic via CYP3A4 isoenzyme, with major metabolite norpropoxyphene (which contributes to cardiotoxicity). |
| Excretion | Primarily hepatic metabolism to norpropoxyphene, then renal excretion of metabolites; <20% excreted unchanged in urine; minor biliary/fecal elimination. |
| Half-life | 6-12 hours (parent drug); norpropoxyphene half-life 30-36 hours, accumulates with repeated dosing, increasing risk of toxicity. |
| Protein binding | Approximately 80% bound primarily to albumin. |
| Volume of Distribution | 12-26 L/kg; high Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: 30-70% due to first-pass metabolism; erratic and variable. |
| Onset of Action | Oral: 30-60 minutes. |
| Duration of Action | 4-6 hours (analgesic effect); respiratory depression may persist longer due to norpropoxyphene accumulation. |
| Molecular Weight | 375.5 |
| Action Class | Progestins (First generation) |
| Brand Substitutes | Pregaphase 500mg Injection, Oxyron 500 Injection, Eutrion H 500mg Injection, Hergest Injection, Cantogest Injection |
Propoxyphene hydrochloride (Darvon) for moderate to severe pain: 65 mg orally every 4 hours as needed; maximum 390 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: administer 65 mg every 6 hours; GFR <10 mL/min: avoid or reduce dose to 65 mg every 8 hours due to accumulation of norpropoxyphene. |
| Liver impairment | Child-Pugh class B or C: contraindicated; mild hepatic impairment: reduce dose to 65 mg every 6 hours and monitor closely. |
| Pediatric use | Not recommended for children under 12 years; for older children: 0.5-1 mg/kg/dose every 4 hours as needed, maximum 2 mg/kg/day. |
| Geriatric use | Initiate at 65 mg every 6 hours; monitor for respiratory depression, dizziness, and constipation; avoid in elderly with renal or hepatic impairment. |
| 1st trimester | Avoid due to association with congenital heart defects and neural tube defects in early pregnancy. |
| 2nd trimester | Use only if clearly needed; may cause fetal respiratory depression and physical dependence. |
| 3rd trimester | Prolonged use may lead to neonatal opioid withdrawal syndrome. Avoid during labor to prevent neonatal respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for DARVON (DARVON).
| Placental transfer | Crosses placenta readily; detectable in fetal tissues and amniotic fluid. |
| Breastfeeding | Enters breast milk in low concentrations. Infant exposure is generally low, but monitor for sedation and poor feeding. Consider risk of neonatal withdrawal if mother used chronically. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited data, but no clear evidence of major malformations. Second and third trimesters: Risk of neonatal respiratory depression and withdrawal if used near term or in high doses. Chronic use may lead to neonatal opioid withdrawal syndrome. |
| Fetal Monitoring | Monitor maternal respiratory status, sedation level, and signs of abuse. Fetal: monitor heart rate and growth if chronic use. Neonatal: observe for withdrawal symptoms (irritability, tremors, respiratory distress) and respiratory depression if used near delivery. |
| Fertility Effects | May decrease libido and cause menstrual irregularities. No clear evidence of permanent impairment; effects typically reversible upon discontinuation. |
■ FDA Black Box Warning
Propoxyphene is associated with fatal respiratory depression, especially when used in doses higher than recommended or in patients with respiratory compromise. Due to the risk of overdose and QT interval prolongation, propoxyphene was withdrawn from the U.S. market in 2010.
| Serious Effects |
Hypersensitivity to propoxyphene or any componentSignificant respiratory depressionAcute or severe bronchial asthmaGI obstruction (e.g., paralytic ileus)Concurrent use of MAOIs or within 14 daysSuicidal tendency or addiction-prone patients
| Precautions | Risk of respiratory depression, Risk of QT prolongation and torsades de pointes, Risk of abuse, addiction, and diversion, Fatal overdose even at therapeutic doses, May cause CNS depression, Use caution in elderly, debilitated, or patients with renal/hepatic impairment |
| Food/Dietary | Grapefruit and grapefruit juice may increase propoxyphene levels; avoid concurrent consumption. Alcohol consumption is contraindicated due to additive CNS depression and increased risk of hepatotoxicity. |
| Clinical Pearls | Darvon (propoxyphene) is a weak opioid analgesic; due to risk of QT prolongation and cardiac arrhythmias, it was withdrawn from the US market in 2010. Consider monitoring ECG in patients with cardiac history or concurrent use of QT-prolonging agents. Propoxyphene has a narrow therapeutic index; overdose can cause seizures, respiratory depression, and cardiac toxicity. Combination with alcohol or CNS depressants increases risk of fatal respiratory depression. |
| Patient Advice | Do not exceed prescribed dose as overdose can be life-threatening. · Avoid alcohol and other CNS depressants while taking this medication. · May cause dizziness or drowsiness; avoid driving or operating machinery until effects are known. · Take exactly as prescribed; do not share with others. · Seek emergency care for signs of overdose: slow breathing, severe drowsiness, or fainting. |
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