DARVOCET A500

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DARVOCET A500 (DARVOCET A500).

How it works

Combination analgesic: acetaminophen inhibits cyclooxygenase (COX) and modulates endocannabinoid system; propoxyphene is a mu-opioid receptor agonist.

What the body does with it

Metabolism	Propoxyphene: hepatic via CYP3A4 and CYP2D6; active metabolite norpropoxyphene. Acetaminophen: hepatic via conjugation (glucuronidation, sulfation) and CYP2E1.
Excretion	Propoxyphene: ~20-25% renal as unchanged drug, ~35% as norpropoxyphene, ~20% biliary/fecal. Acetaminophen: ~2-4% renal unchanged, ~85% as glucuronide and sulfate conjugates, ~5% as cysteine and mercapturate conjugates.
Half-life	Propoxyphene: 6-12 hours (terminal, prolonged in elderly, hepatic impairment, or overdose). Acetaminophen: 2-3 hours (terminal, prolonged in hepatic impairment or overdose).
Protein binding	Propoxyphene: ~78% bound to albumin. Acetaminophen: 10-25% bound (minimal).
Volume of Distribution	Propoxyphene: 16 L/kg (extensive tissue distribution). Acetaminophen: 0.9 L/kg.
Bioavailability	Propoxyphene: 30-70% (first-pass metabolism). Acetaminophen: ~88% (oral).
Onset of Action	Oral: 30-60 minutes (both components).
Duration of Action	Analgesia: 4-6 hours (propoxyphene effect). Acetaminophen: 4-6 hours.

Classification & Brands

Dosing & administration

One tablet (500 mg acetaminophen, 100 mg propoxyphene napsylate) orally every 4 hours as needed for pain; maximum 6 tablets per day.

Dosage form	TABLET
Renal impairment	Contraindicated in severe renal impairment (CrCl <30 mL/min). For GFR 30-50 mL/min: reduce dose to 1 tablet every 6 hours. Monitor for propoxyphene accumulation.
Liver impairment	Avoid use in Child-Pugh class C (severe hepatic impairment). In Child-Pugh class A or B: use with caution, reduce dose by 50% (e.g., 1 tablet every 6-8 hours), and avoid chronic use due to acetaminophen toxicity risk.
Pediatric use	Not recommended for pediatric use due to safety concerns (propoxyphene associated with respiratory depression in children). For adolescents >12 years: 1 tablet every 4 hours as needed; maximum 6 tablets/day.
Geriatric use	Start at 1 tablet every 6-8 hours; avoid exceeding 4 tablets/day. Monitor for CNS depression, constipation, and falls. Consider decreased hepatic/renal function and increased sensitivity.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DARVOCET A500 (DARVOCET A500).

Breastfeeding	Propoxyphene and acetaminophen are excreted into breast milk. M/P ratio for propoxyphene ~0.5-1.0; low relative infant dose (~2% maternal). Acetaminophen M/P ~0.9. Use caution; monitor infant for sedation, poor feeding. AAP considers compatible.
Teratogenic Risk	First trimester: Propoxyphene crosses placenta, limited data; possible association with neural tube defects. Second trimester: Avoid; risk of fetal respiratory depression. Third trimester: Avoid; neonatal withdrawal syndrome (tremors, hypertonia) and respiratory depression at delivery.

Warnings & precautions

■ FDA Black Box Warning

Propoxyphene is associated with fatal respiratory depression, abuse potential, and risk of overdose; contraindicated in patients with suicidal ideation or addiction.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to propoxyphene or acetaminophen, significant respiratory depression, acute or severe bronchial asthma, paralytic ileus, known CYP2D6 ultrarapid metabolizers, concomitant use of MAOIs or within 14 days, suicidal patients, addiction-prone individuals.

Clinical Precautions

Precautions

Risk of respiratory depression, abuse and dependence, cardiac toxicity (QT prolongation, arrhythmias), acetaminophen hepatotoxicity, increased seizure risk in patients with CNS depression, interaction with CNS depressants.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

DARVOCET A500

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DARVOCET A500 (DARVOCET A500).

How it works

Combination analgesic: acetaminophen inhibits cyclooxygenase (COX) and modulates endocannabinoid system; propoxyphene is a mu-opioid receptor agonist.

What the body does with it

Metabolism	Propoxyphene: hepatic via CYP3A4 and CYP2D6; active metabolite norpropoxyphene. Acetaminophen: hepatic via conjugation (glucuronidation, sulfation) and CYP2E1.
Excretion	Propoxyphene: ~20-25% renal as unchanged drug, ~35% as norpropoxyphene, ~20% biliary/fecal. Acetaminophen: ~2-4% renal unchanged, ~85% as glucuronide and sulfate conjugates, ~5% as cysteine and mercapturate conjugates.
Half-life	Propoxyphene: 6-12 hours (terminal, prolonged in elderly, hepatic impairment, or overdose). Acetaminophen: 2-3 hours (terminal, prolonged in hepatic impairment or overdose).
Protein binding	Propoxyphene: ~78% bound to albumin. Acetaminophen: 10-25% bound (minimal).
Volume of Distribution	Propoxyphene: 16 L/kg (extensive tissue distribution). Acetaminophen: 0.9 L/kg.
Bioavailability	Propoxyphene: 30-70% (first-pass metabolism). Acetaminophen: ~88% (oral).
Onset of Action	Oral: 30-60 minutes (both components).
Duration of Action	Analgesia: 4-6 hours (propoxyphene effect). Acetaminophen: 4-6 hours.

Classification & Brands

Dosing & administration

One tablet (500 mg acetaminophen, 100 mg propoxyphene napsylate) orally every 4 hours as needed for pain; maximum 6 tablets per day.

Dosage form	TABLET
Renal impairment	Contraindicated in severe renal impairment (CrCl <30 mL/min). For GFR 30-50 mL/min: reduce dose to 1 tablet every 6 hours. Monitor for propoxyphene accumulation.
Liver impairment	Avoid use in Child-Pugh class C (severe hepatic impairment). In Child-Pugh class A or B: use with caution, reduce dose by 50% (e.g., 1 tablet every 6-8 hours), and avoid chronic use due to acetaminophen toxicity risk.
Pediatric use	Not recommended for pediatric use due to safety concerns (propoxyphene associated with respiratory depression in children). For adolescents >12 years: 1 tablet every 4 hours as needed; maximum 6 tablets/day.
Geriatric use	Start at 1 tablet every 6-8 hours; avoid exceeding 4 tablets/day. Monitor for CNS depression, constipation, and falls. Consider decreased hepatic/renal function and increased sensitivity.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DARVOCET A500 (DARVOCET A500).

Breastfeeding	Propoxyphene and acetaminophen are excreted into breast milk. M/P ratio for propoxyphene ~0.5-1.0; low relative infant dose (~2% maternal). Acetaminophen M/P ~0.9. Use caution; monitor infant for sedation, poor feeding. AAP considers compatible.
Teratogenic Risk	First trimester: Propoxyphene crosses placenta, limited data; possible association with neural tube defects. Second trimester: Avoid; risk of fetal respiratory depression. Third trimester: Avoid; neonatal withdrawal syndrome (tremors, hypertonia) and respiratory depression at delivery.

Warnings & precautions

■ FDA Black Box Warning

Propoxyphene is associated with fatal respiratory depression, abuse potential, and risk of overdose; contraindicated in patients with suicidal ideation or addiction.