DARVON-N

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DARVON-N (DARVON-N).

How it works

Propoxyphene is a weak mu-opioid receptor agonist that produces analgesia by binding to opioid receptors in the central nervous system, altering the perception of and response to pain. Its metabolite norpropoxyphene has local anesthetic and sodium channel blocking effects, which may contribute to cardiac toxicity.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 and CYP2D6 to norpropoxyphene (active metabolite). Propoxyphene and norpropoxyphene undergo further metabolism and conjugation.
Excretion	Primarily renal (approximately 70% as unchanged drug and glucuronide conjugates); minor biliary/fecal elimination (25-30%).
Half-life	Propoxyphene: 6-12 hours; norpropoxyphene: 30-36 hours. Accumulation of norpropoxyphene on repeated dosing increases risk of toxicity.
Protein binding	Propoxyphene: 70-80%; norpropoxyphene: 75-85%. Primarily bound to albumin.
Volume of Distribution	Propoxyphene: 12-26 L/kg; widely distributed into tissues, including CNS.
Bioavailability	Oral: approximately 30-70% due to extensive first-pass metabolism; interindividual variability.
Onset of Action	Oral: 30-60 minutes; peak effect at 2 hours.
Duration of Action	4-6 hours for pain relief; analgesic effect may persist longer with accumulation.

Classification & Brands

Dosing & administration

100 mg orally every 4 hours as needed for pain; maximum 600 mg per day.

Dosage form	SUSPENSION
Renal impairment	GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: reduce dose by 50% or extend interval to every 8-12 hours; not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use.
Pediatric use	Not recommended for children under 12 years; for adolescents 12-17 years: 100 mg every 4 hours as needed, maximum 400 mg per day.
Geriatric use	Initiate at 50 mg every 4 hours as needed; maximum 400 mg per day; monitor for CNS depression and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DARVON-N (DARVON-N).

Breastfeeding	Propoxyphene is excreted into breast milk with a milk-to-plasma ratio of approximately 1.0. Theoretical risk of neonatal respiratory depression and withdrawal. Not recommended; consider alternative analgesics.
Teratogenic Risk	First trimester: Limited data; potential for neural tube defects with first-trimester exposure. Second and third trimesters: Risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal withdrawal syndrome. Use only if clearly needed.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

DARVON-N (propoxyphene) is contraindicated in patients with a history of drug abuse, and its use should be monitored for signs of abuse, addiction, or misuse. It should not be used in patients with severe respiratory depression, acute or severe bronchial asthma, or known hypersensitivity to propoxyphene. Additionally, because of the risk of QT prolongation and cardiac arrhythmias, propoxyphene-containing products were withdrawn from the US market in 2010.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to propoxyphene or any component","Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting","Known or suspected gastrointestinal obstruction (e.g., paralytic ileus)","Concurrent use of alcohol, sedatives, or other CNS depressants","History of substance abuse","Concurrent MAOIs or within 14 days"]

Clinical Precautions

Precautions

["Addiction, abuse, and misuse","Respiratory depression","Accidental ingestion (especially in children) can be fatal","Neonatal opioid withdrawal syndrome","Interactions with CNS depressants (e.g., alcohol, benzodiazepines)","Elderly or debilitated patients: increased risk of respiratory depression","Hepatic or renal impairment","QT prolongation and risk of torsade de pointes"]

Clinical Tips & Counseling

Drug interactions

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DARVON-N

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DARVON-N (DARVON-N).

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 and CYP2D6 to norpropoxyphene (active metabolite). Propoxyphene and norpropoxyphene undergo further metabolism and conjugation.
Excretion	Primarily renal (approximately 70% as unchanged drug and glucuronide conjugates); minor biliary/fecal elimination (25-30%).
Half-life	Propoxyphene: 6-12 hours; norpropoxyphene: 30-36 hours. Accumulation of norpropoxyphene on repeated dosing increases risk of toxicity.
Protein binding	Propoxyphene: 70-80%; norpropoxyphene: 75-85%. Primarily bound to albumin.
Volume of Distribution	Propoxyphene: 12-26 L/kg; widely distributed into tissues, including CNS.
Bioavailability	Oral: approximately 30-70% due to extensive first-pass metabolism; interindividual variability.
Onset of Action	Oral: 30-60 minutes; peak effect at 2 hours.
Duration of Action	4-6 hours for pain relief; analgesic effect may persist longer with accumulation.

Classification & Brands

Dosing & administration

100 mg orally every 4 hours as needed for pain; maximum 600 mg per day.

Dosage form	SUSPENSION
Renal impairment	GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: reduce dose by 50% or extend interval to every 8-12 hours; not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use.
Pediatric use	Not recommended for children under 12 years; for adolescents 12-17 years: 100 mg every 4 hours as needed, maximum 400 mg per day.
Geriatric use	Initiate at 50 mg every 4 hours as needed; maximum 400 mg per day; monitor for CNS depression and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DARVON-N (DARVON-N).

Breastfeeding	Propoxyphene is excreted into breast milk with a milk-to-plasma ratio of approximately 1.0. Theoretical risk of neonatal respiratory depression and withdrawal. Not recommended; consider alternative analgesics.
Teratogenic Risk	First trimester: Limited data; potential for neural tube defects with first-trimester exposure. Second and third trimesters: Risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal withdrawal syndrome. Use only if clearly needed.
Fetal Monitoring