Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DARVON COMPOUND vs ANEXSIA 5/325
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Darvon Compound is a combination of propoxyphene, aspirin, and caffeine. Propoxyphene is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Aspirin inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing anti-inflammatory and analgesic effects. Caffeine is a CNS stimulant that may enhance analgesia through adenosine receptor antagonism.
Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.
Management of mild to moderate pain,As an antipyretic (aspirin component),Off-label: Not commonly used due to safety concerns
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
One capsule (propoxyphene HCl 65 mg, aspirin 389 mg, caffeine 32.4 mg) orally every 4 hours as needed for pain. Maximum 6 capsules per day.
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Propoxyphene: 6-12 hours (terminal, prolonged in overdose due to enterohepatic recirculation). Acetaminophen: 2-3 hours (terminal). Clinical context: accumulation in elderly, hepatic impairment.
Oxycodone: terminal half-life 3.2-4.3 hours (immediate-release); prolonged in hepatic impairment. Acetaminophen: terminal half-life 2-3 hours (therapeutic doses); prolonged in hepatic impairment or overdose.
Propoxyphene: Hepatic via CYP3A4 to norpropoxyphene (active metabolite); Aspirin: Hydrolyzed by esterases to salicylate, further conjugated in the liver; Caffeine: Hepatic via CYP1A2 to paraxanthine, theobromine, and theophylline.
Hydrocodone: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (hydromorphone). Acetaminophen: hepatic metabolism via conjugation (glucuronidation, sulfation) and CYP2E1-mediated oxidation to toxic NAPQI.
Renal: ~70% as unchanged drug and glucuronide conjugates (propoxyphene and acetaminophen). Fecal: <10% as unchanged and metabolites. Biliary: minor route for propoxyphene conjugates.
Oxycodone: renal excretion of metabolites (conjugated and unconjugated) and parent drug; ~10% excreted unchanged. Acetaminophen: renal excretion of metabolites (glucuronide and sulfate conjugates); ~2-4% excreted unchanged.
Propoxyphene: ~80% (albumin). Acetaminophen: 10-25% (albumin; lower at toxic concentrations).
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
Propoxyphene: 0.9-1.2 L/kg (wide distribution, high tissue binding). Acetaminophen: 0.8-1.0 L/kg (uniform distribution).
Oxycodone: Vd 2.0-3.0 L/kg; distributes extensively into tissues. Acetaminophen: Vd 0.8-1.0 L/kg; relatively uniform distribution.
Propoxyphene: 30-70% (first-pass metabolism, dose-dependent; higher with food). Acetaminophen: 60-90% (oral, variable first-pass; >95% for rectal? Not applicable here).
Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses).
Contraindicated in severe renal impairment (e GFR <30 m L/min). For moderate impairment (e GFR 30-59 m L/min): reduce dose to 1 capsule every 6 hours; maximum 4 capsules/day. Avoid in ESRD.
GFR 30-50 m L/min: use with caution, increase dosing interval to every 6 hours; GFR <30 m L/min: avoid use due to hydrocodeone accumulation.
Contraindicated in Child-Pugh class C. For Child-Pugh class A or B: reduce dose by 50% (max 3 capsules/day) and monitor for sedation and respiratory depression.
Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
Not recommended for pediatric patients due to risk of propoxyphene cardiotoxicity and aspirin-associated Reye's syndrome in viral illness.
Not recommended for children under 18 years due to risk of respiratory depression.
Initiate with 1 capsule every 6 hours; maximum 4 capsules/day. Avoid in patients >80 years due to increased risk of CNS depression, falls, and bleeding from aspirin.
Start with lowest dose (1 tablet every 6 hours), monitor renal and hepatic function, and avoid in frail elderly due to increased fall and cognitive impairment risk.
Propoxyphene has been withdrawn from the U. S. market due to risk of fatal overdose (QT prolongation and cardiac arrhythmias). Use is contraindicated in patients at risk for QT prolongation. Avoid concurrent use with CYP3A4 inhibitors.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and hepatotoxicity from acetaminophen overdose.
Risk of fatal overdose (QT prolongation, cardiac arrest); respiratory depression; drug dependence and abuse; caution in renal or hepatic impairment; avoid in patients with bleeding disorders (aspirin); Reye's syndrome risk in children with viral illness; caffeine may worsen anxiety or insomnia.
Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity; adrenal insufficiency; severe hypotension; gastrointestinal obstruction; seizure; and serotonin syndrome.
Hypersensitivity to propoxyphene, aspirin, caffeine, or NSAIDs; patients with QT interval prolongation or on QT-prolonging drugs; concurrent use of CYP3A4 inhibitors (e.g., ketoconazole, ritonavir); children with viral illness (Reye's syndrome risk); severe renal or hepatic impairment; asthma or nasal polyps (aspirin sensitivity); active peptic ulcer disease or bleeding disorders.
Hypersensitivity to hydrocodone or acetaminophen; significant respiratory depression; acute or severe bronchial asthma; GI obstruction; known or suspected paralytic ileus; severe hepatic impairment; and concurrent use of MAOIs within 14 days.
Avoid alcohol, as it increases propoxyphene CNS depression and hepatotoxicity. Limit caffeine-containing foods/beverages due to additive effects with caffeine component. Aspirin absorption is delayed by food; take on empty stomach for faster relief, but with food if GI upset occurs.
Avoid alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
Darvon Compound contains propoxyphene and acetaminophen. Propoxyphene: FDA pregnancy category C; risk of respiratory depression in neonates if used near term; increased risk of premature labor and low birth weight with chronic use; possible congenital malformations (cleft palate, cardiac defects) in first trimester based on animal studies. Acetaminophen: generally considered low risk in pregnancy; no consistent evidence of teratogenicity. Avoid in third trimester due to risk of neonatal withdrawal syndrome.
First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal renal toxicity, oligohydramnios, and premature closure of ductus arteriosus. Use only if clearly needed.
Propoxyphene excreted in breast milk in low concentrations (M/P ratio ~0.2); may cause sedation or respiratory depression in infants; avoid use in breastfeeding due to potential CNS effects. Acetaminophen M/P ratio ~0.9-1.0, considered compatible at recommended doses.
Paracetamol and hydrocodone are excreted in breast milk. M/P ratio: paracetamol ~1.0, hydrocodone ~1.0-2.0. Use with caution; monitor infant for drowsiness and respiratory depression. Consider risk of infant sedation with long-term use.
Due to increased plasma volume and hepatic metabolism during pregnancy, propoxyphene clearance may be increased, potentially requiring dose adjustments; however, due to risk of neonatal respiratory depression and withdrawal, avoid use or use lowest effective dose for shortest duration. Acetaminophen pharmacokinetics minimally altered; standard dosing applies.
Increased clearance in pregnancy may require dose adjustment. Monitor for pain control and adverse effects; no fixed dose change recommended. Consider lower starting dose due to potential fetal risks. Avoid chronic use; taper if possible.
Darvon Compound contains propoxyphene, aspirin, and caffeine. Due to propoxyphene's risk of QT prolongation and fatal arrhythmias, especially at supratherapeutic doses, it was withdrawn from the US market in 2010. Use is contraindicated in patients with prolonged QT interval, electrolyte disturbances, or on other QT-prolonging drugs. Aspirin component requires caution in bleeding disorders, peptic ulcer disease, and children with viral illness due to Reye's syndrome risk. Caffeine may exacerbate anxiety or insomnia.
ANEXSIA 5/325 contains hydrocodone 5 mg and acetaminophen 325 mg. Maximum acetaminophen dose from all sources should not exceed 4 g/day in adults; avoid in severe hepatic impairment. Hydrocodone is a Schedule II controlled substance with abuse potential; monitor for respiratory depression, especially in opioid-naive patients. Use with caution in patients with COPD, sleep apnea, or increased intracranial pressure. Consider naloxone co-prescription for high-risk patients. For acute pain, limit duration to 3-7 days.
Do not exceed recommended dose; propoxyphene overdose can cause life-threatening heart rhythm problems.,Avoid alcohol and other CNS depressants while taking this medication.,If you have a history of heart disease, low potassium/magnesium, or take other medications, inform your doctor.,Aspirin may increase bleeding risk; avoid if you have stomach ulcers or take blood thinners.,Discontinue and seek medical attention if you experience fainting, rapid heartbeat, or signs of allergic reaction.,Keep out of reach of children; accidental overdose can be fatal.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Do not consume alcohol or other sedatives (e.g., benzodiazepines) while taking this medication.,Avoid other products containing acetaminophen (e.g., Tylenol, cold remedies) to prevent liver damage.,This medication may cause drowsiness or dizziness; do not drive or operate machinery until you know how it affects you.,Store securely out of reach of others; dispose of unused medication via drug take-back programs.,Seek emergency help if you have trouble breathing, severe drowsiness, or signs of allergic reaction.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about DARVON COMPOUND vs ANEXSIA 5/325, answered by our medical review team.
DARVON COMPOUND is a Opioid Analgesic Combination that works by Darvon Compound is a combination of propoxyphene, aspirin, and caffeine. Propoxyphene is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Aspirin inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing anti-inflammatory and analgesic effects. Caffeine is a CNS stimulant that may enhance analgesia through adenosine receptor antagonism.. ANEXSIA 5/325 is a Opioid Analgesic Combination that works by Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DARVON COMPOUND and ANEXSIA 5/325 depend on the specific clinical indication. These are both Opioid Analgesic Combination agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of DARVON COMPOUND is: One capsule (propoxyphene HCl 65 mg, aspirin 389 mg, caffeine 32.4 mg) orally every 4 hours as needed for pain. Maximum 6 capsules per day.. The standard adult dose of ANEXSIA 5/325 is: 1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between DARVON COMPOUND and ANEXSIA 5/325 in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. DARVON COMPOUND is classified as Category C. Darvon Compound contains propoxyphene and acetaminophen. Propoxyphene: FDA pregnancy category C; risk of respiratory depression in neonates if used near term; increased risk of pre. ANEXSIA 5/325 is classified as Category C. First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal re. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.