PROPOXYPHENE HYDROCHLORIDE 65

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROPOXYPHENE HYDROCHLORIDE 65 (PROPOXYPHENE HYDROCHLORIDE 65).

How it works

Propoxyphene is a centrally acting opioid agonist that binds to mu-opioid receptors in the central nervous system, inhibiting pain signal transmission and altering pain perception. It also has local anesthetic effects.

What the body does with it

Metabolism	Primarily hepatic via N-demethylation (CYP3A4) to norpropoxyphene, an active metabolite with longer half-life and potential for toxicity.
Excretion	Renal excretion of unchanged drug (approximately 20-30%) and metabolites; approximately 40-60% as conjugated metabolites; minor biliary/fecal elimination.
Half-life	6-12 hours (mean ~8 hours); prolonged in hepatic impairment and elderly; accumulation possible with repeated dosing.
Protein binding	40-50% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	8-16 L/kg; extensive tissue distribution, including CNS.
Bioavailability	Oral: 30-70% due to first-pass metabolism.
Onset of Action	Oral: 30-60 minutes.
Duration of Action	4-6 hours; longer with hepatic impairment or in elderly patients.

Classification & Brands

Dosing & administration

65 mg orally every 4 hours as needed for pain; maximum 390 mg/day.

Dosage form	CAPSULE
Renal impairment	GFR 10-50 mL/min: administer 50% of normal dose every 6 hours. GFR <10 mL/min: administer 50% of normal dose every 6-8 hours or avoid use; increase risk of accumulation of toxic metabolite norpropoxyphene.
Liver impairment	Child-Pugh Class A and B: reduce dose by 50% and extend dosing interval to every 6-8 hours. Child-Pugh Class C: contraindicated due to risk of accumulation and toxicity; alternative therapy recommended.
Pediatric use	Not recommended for use in children due to risk of respiratory depression and toxicity. No established weight-based dosing guidelines.
Geriatric use	Initiate at 50% of adult dose (e.g., 32.5 mg) every 6 hours as needed; cautiously titrate due to prolonged half-life, increased CNS sensitivity, and risk of falls. Avoid use if possible; alternative safer analgesics recommended.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PROPOXYPHENE HYDROCHLORIDE 65 (PROPOXYPHENE HYDROCHLORIDE 65).

Breastfeeding	Excreted in breast milk; M/P ratio 0.27. Use with caution; monitor infant for sedation, respiratory depression. Consider alternative analgesia.
Teratogenic Risk	First trimester: Limited human data; animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: Associated with neonatal respiratory depression, withdrawal syndrome if chronic use near term. Avoid prolonged use.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Propoxyphene is associated with a risk of fatal respiratory depression, especially when used in higher doses, in elderly patients, or in combination with other CNS depressants. It increases the risk of QT prolongation and fatal arrhythmias, leading to its withdrawal from the market in some countries.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to propoxyphene or any component","Significant respiratory depression","Acute or severe bronchial asthma","Paralytic ileus","Concurrent use with QT-prolonging drugs or in patients with known QT prolongation"]

Clinical Precautions

Precautions

["Risk of respiratory depression, especially in elderly, debilitated, or opioid-naive patients","QT prolongation and risk of torsade de pointes, particularly with doses >400 mg/day","Dependence, abuse, and tolerance potential","Concomitant use with alcohol or CNS depressants increases toxicity risk","Use in hepatic or renal impairment requires dose adjustment"]

Clinical Tips & Counseling

Drug interactions

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PROPOXYPHENE HYDROCHLORIDE 65

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROPOXYPHENE HYDROCHLORIDE 65 (PROPOXYPHENE HYDROCHLORIDE 65).

How it works

What the body does with it

Metabolism	Primarily hepatic via N-demethylation (CYP3A4) to norpropoxyphene, an active metabolite with longer half-life and potential for toxicity.
Excretion	Renal excretion of unchanged drug (approximately 20-30%) and metabolites; approximately 40-60% as conjugated metabolites; minor biliary/fecal elimination.
Half-life	6-12 hours (mean ~8 hours); prolonged in hepatic impairment and elderly; accumulation possible with repeated dosing.
Protein binding	40-50% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	8-16 L/kg; extensive tissue distribution, including CNS.
Bioavailability	Oral: 30-70% due to first-pass metabolism.
Onset of Action	Oral: 30-60 minutes.
Duration of Action	4-6 hours; longer with hepatic impairment or in elderly patients.

Classification & Brands

Dosing & administration

65 mg orally every 4 hours as needed for pain; maximum 390 mg/day.

Dosage form	CAPSULE
Renal impairment	GFR 10-50 mL/min: administer 50% of normal dose every 6 hours. GFR <10 mL/min: administer 50% of normal dose every 6-8 hours or avoid use; increase risk of accumulation of toxic metabolite norpropoxyphene.
Liver impairment	Child-Pugh Class A and B: reduce dose by 50% and extend dosing interval to every 6-8 hours. Child-Pugh Class C: contraindicated due to risk of accumulation and toxicity; alternative therapy recommended.
Pediatric use	Not recommended for use in children due to risk of respiratory depression and toxicity. No established weight-based dosing guidelines.
Geriatric use	Initiate at 50% of adult dose (e.g., 32.5 mg) every 6 hours as needed; cautiously titrate due to prolonged half-life, increased CNS sensitivity, and risk of falls. Avoid use if possible; alternative safer analgesics recommended.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PROPOXYPHENE HYDROCHLORIDE 65 (PROPOXYPHENE HYDROCHLORIDE 65).

Breastfeeding	Excreted in breast milk; M/P ratio 0.27. Use with caution; monitor infant for sedation, respiratory depression. Consider alternative analgesia.
Teratogenic Risk	First trimester: Limited human data; animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: Associated with neonatal respiratory depression, withdrawal syndrome if chronic use near term. Avoid prolonged use.
Fetal Monitoring