Comparative Pharmacology
Head-to-head clinical analysis: DARVON versus OXYMORPHONE HYDROCHLORIDE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DARVON versus OXYMORPHONE HYDROCHLORIDE.
DARVON vs OXYMORPHONE HYDROCHLORIDE
Head-to-head clinical comparison of therapeutic indices and safety profiles.
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.
Oxymorphone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the central nervous system, inhibiting ascending pain pathways and altering pain perception and response. It also has affinity for kappa and delta opioid receptors.
Management of mild to moderate pain
Moderate to severe pain where an opioid analgesic is appropriateOff-label: management of pain not responsive to non-opioid analgesics
Propoxyphene hydrochloride (Darvon) for moderate to severe pain: 65 mg orally every 4 hours as needed; maximum 390 mg/day.
Initial: 1 mg IV/IM every 3-4 hours as needed for moderate to severe pain; titrate to effect. For patient-controlled analgesia (PCA), 0.5 mg IV loading dose, then 0.25-0.5 mg every 6-15 minutes with lockout. Rectal suppository: 5 mg every 4-6 hours.
None Documented
None Documented
6-12 hours (parent drug); norpropoxyphene half-life 30-36 hours, accumulates with repeated dosing, increasing risk of toxicity.
Terminal elimination half-life: 7-9 hours (range 4-12 h in elderly/renal impairment). Clinically, steady-state achieved within 24-36 hours.
Primarily hepatic via CYP3A4 isoenzyme, with major metabolite norpropoxyphene (which contributes to cardiotoxicity).
Primarily hepatic via glucuronidation (UGT2B7) to oxymorphone-3-glucuronide; minor CYP450 involvement (CYP3A4 and CYP2C9).
Primarily hepatic metabolism to norpropoxyphene, then renal excretion of metabolites; <20% excreted unchanged in urine; minor biliary/fecal elimination.
Primarily renal (90% as parent drug and metabolites); <1% fecal. Unchanged oxymorphone accounts for ~30% of urinary recovery.
Approximately 80% bound primarily to albumin.
Approximately 10-12%; primarily bound to albumin.
12-26 L/kg; high Vd indicates extensive tissue distribution.
Vd: 1.5-3.7 L/kg; indicates extensive tissue distribution (e.g., brain, adipose). Higher Vd may require dose adjustment in obese patients.
Oral: 30-70% due to first-pass metabolism; erratic and variable.
Oral (immediate-release): 10-15% (extensive first-pass metabolism); Oral (extended-release): 10-15%; Intramuscular: equivalent to IV (100% relative to IV but with slower absorption).
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.
CrCl 30-59: Administer 75% of normal dose; CrCl 15-29: Administer 50% of normal dose; CrCl <15: Avoid use or administer 25% of normal dose with extended dosing interval (e.g., every 6-8 hours).
Child-Pugh class B or C: contraindicated; mild hepatic impairment: reduce dose to 65 mg every 6 hours and monitor closely.
Child-Pugh Class A: No adjustment necessary; Child-Pugh Class B: Reduce initial dose by 50% and titrate cautiously; Child-Pugh Class C: Avoid use or administer 25% of normal dose with prolonged interval.
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.
Not FDA-approved for pediatric use. Limited data: IV/IM 0.1-0.2 mg/kg every 4-6 hours as needed (max 3 mg/dose).
Initiate at 65 mg every 6 hours; monitor for respiratory depression, dizziness, and constipation; avoid in elderly with renal or hepatic impairment.
Initiate at 0.5-1 mg IV/IM every 4-6 hours; titrate slowly. Consider 50% dose reduction due to increased sensitivity and risk of respiratory depression.
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.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion (especially in children); neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks from concomitant use with benzodiazepines or other CNS depressants.
["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"]
Respiratory depression; CNS depression; addiction potential; hypotension; seizures; increased intracranial pressure; biliary tract disease; pancreatitis; severe renal impairment; elderly and debilitated patients; adrenal insufficiency; severe hepatic impairment; concurrent use with MAOIs or serotonergic drugs.
["Hypersensitivity to propoxyphene","Significant respiratory depression","Acute or severe bronchial asthma","Suspected paralytic ileus","Concomitant use of MAO inhibitors or within 14 days","Concomitant use of CYP3A4 inhibitors (e.g., ketoconazole, erythromycin)"]
Hypersensitivity to oxymorphone or any component; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting; known or suspected paralytic ileus; gastrointestinal obstruction; postpartum analgesia (for the injection form).
Data Pending Review
Data Pending Review
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.
Avoid grapefruit and grapefruit juice as they may inhibit CYP3A4 metabolism, increasing oxymorphone levels and risk of adverse effects. Alcohol should be strictly avoided due to additive CNS depression and increased risk of respiratory depression. No other clinically significant food interactions are reported.
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.
Opioid analgesics cross the placenta. First trimester: Limited data, but no clear evidence of major malformations; however, use associated with neural tube defects in some studies. Second and third trimesters: Chronic use may lead to fetal dependence and neonatal opioid withdrawal syndrome (NOWS) after delivery. Use during labor may cause respiratory depression in the newborn.
Enters breast milk. M/P ratio approximately 1.0. Use caution; monitor infant for drowsiness, respiratory depression, and poor feeding. American Academy of Pediatrics considers use compatible with breastfeeding with careful monitoring.
Oxymorphone is excreted into breast milk. M/P ratio not determined. The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor infant for signs of respiratory depression and sedation. Use lowest effective dose for shortest duration.
Pharmacokinetic changes: increased clearance and volume of distribution, potentially requiring dose increases to maintain analgesia. Taper slowly to avoid withdrawal; use lowest effective dose for shortest duration.
Pregnancy increases volume of distribution and clearance. Dose requirements may increase by 20-50% in the second and third trimesters to achieve same analgesic effect. Titrate to effect and monitor for maternal respiratory depression. Postpartum, reduce dose to prepregnancy levels.
Category C
Category C
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.
Oxymorphone is approximately 10 times more potent than morphine. It has no ceiling effect for analgesia but dose-limiting adverse effects include respiratory depression and CNS depression. Use with extreme caution in patients with impaired renal function because the drug is primarily excreted unchanged in urine. Avoid use within 14 days of MAO inhibitor therapy. Monitor for opioid-induced constipation and consider prophylactic bowel regimen. For breakthrough pain, immediate-release formulations have an onset of 5-10 minutes intravenously and 15-30 minutes orally.
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.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.Do not crush, chew, or break extended-release tablets; swallow whole.Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of fatal respiratory depression.Do not stop abruptly; withdrawal symptoms may occur. Work with your provider to taper if needed.Store securely out of reach of children and others. Dispose of unused medication via take-back programs.Report any signs of respiratory depression (slow/shallow breathing), severe sedation, or constipation immediately.This medication may impair your ability to drive or operate machinery. Do not perform such tasks until you know how it affects you.Inform all healthcare providers that you are taking this medication.If you are pregnant, plan to become pregnant, or are breastfeeding, discuss risks with your doctor.Avoid grapefruit and grapefruit juice while taking oxymorphone as it may increase side effects.