DARVON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DARVON (DARVON).

How it works

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.

What the body does with it

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.

Classification & Brands

Action Class	Progestins (First generation)
Brand Substitutes	Pregaphase 500mg Injection, Oxyron 500 Injection, Eutrion H 500mg Injection, Hergest Injection, Cantogest Injection

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DARVON (DARVON).

Breastfeeding	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.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["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)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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DARVON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DARVON (DARVON).

How it works

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.

What the body does with it

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.

Classification & Brands

Action Class	Progestins (First generation)
Brand Substitutes	Pregaphase 500mg Injection, Oxyron 500 Injection, Eutrion H 500mg Injection, Hergest Injection, Cantogest Injection

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DARVON (DARVON).

Breastfeeding	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.
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.