Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DARVON W/ ASA 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
Combination analgesic: propoxyphene is a weak opioid agonist binding to mu-opioid receptors, inhibiting ascending pain pathways; aspirin irreversibly inhibits cyclooxygenase-1 and -2, reducing prostaglandin synthesis.
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.
Mild to moderate pain,Pain accompanied by inflammation or fever
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
1 capsule (propoxyphene HCl 65 mg / aspirin 650 mg) orally every 4 hours as needed for pain, not to exceed 6 capsules per day.
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Propoxyphene terminal half-life is 6–12 hours (mean 8 h) in healthy adults; prolonged in hepatic impairment or elderly due to reduced metabolism. Aspirin half-life is 15–20 minutes due to rapid hydrolysis to salicylate.
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 undergoes hepatic metabolism via N-demethylation to norpropoxyphene (active metabolite); both are primarily excreted renally. Aspirin is rapidly hydrolyzed to salicylate, which is metabolized by conjugation and oxidation, with renal excretion.
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 elimination of propoxyphene and its metabolites accounts for ~70% of a dose, with ~20% excreted unchanged in urine; biliary/fecal elimination accounts for ~10%; aspirin is renally excreted as salicylate and its 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 is 70–80% bound to albumin; aspirin is 50–80% bound to albumin (dose-dependent due to saturable binding).
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
Propoxyphene Vd is 6–10 L/kg, indicating extensive tissue distribution; aspirin Vd is 0.15–0.2 L/kg, primarily in plasma and extracellular fluid.
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% oral bioavailability due to first-pass metabolism; aspirin: 50–70% oral bioavailability (first-pass hydrolysis to salicylate).
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/1.73m²). For moderate impairment (e GFR 30-59), reduce dose to 1 capsule every 6 hours. No adjustment needed for mild impairment (e GFR ≥60).
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 B, maximum 2 capsules per day. For Child-Pugh class A, no adjustment required but monitor closely.
Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
Not recommended for children under 12 years. For children 12-18 years: 1 capsule (propoxyphene 65 mg/aspirin 650 mg) every 4 hours as needed, maximum 6 capsules/day. Weight-based dosing not established due to fixed combination.
Not recommended for children under 18 years due to risk of respiratory depression.
Initiate with 1 capsule every 6 hours. Maximum 4 capsules per day due to increased sensitivity and risk of CNS depression and renal impairment. Avoid in patients >75 years or those with frailty.
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 is associated with a risk of fatal respiratory depression, especially in overdose or when combined with CNS depressants. Use with caution in elderly, debilitated, or patients with respiratory compromise.
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 respiratory depression; hepatotoxicity with chronic high doses; GI bleeding, ulceration, and perforation with aspirin; renal toxicity; hypersensitivity reactions; use in elderly, renal/hepatic impairment, or history of alcohol abuse.
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, or NSAIDs; severe respiratory depression; acute or severe asthma; GI bleeding; history of peptic ulcer disease; hemophilia; children with viral infections (Reye's syndrome); concurrent MAOIs or alcohol.
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. Aspirin component may cause gastrointestinal irritation; take with food or milk to reduce stomach upset. Avoid foods high in tyramine (e.g., aged cheese, processed meats) as propoxyphene may have weak MAOI activity? Not established but caution advised.
Avoid alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
First trimester: Aspirin component associated with increased risk of neural tube defects and gastroschisis. Propoxyphene not associated with major malformations but data limited. Second trimester: Aspirin risk increases for fetal intracranial hemorrhage with chronic use. Third trimester: Aspirin may cause premature closure of ductus arteriosus, oligohydramnios, and increased perinatal hemorrhage. Propoxyphene may cause 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.
Aspirin enters breast milk in low amounts; M/P ratio ~0.1. Propoxyphene M/P ratio ~0.5. Both can accumulate in neonates with repeated dosing. Potential for infant sedation, respiratory depression, and Reye's syndrome. Contraindicated in breastfeeding due to risks.
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.
No specific dose adjustments in pregnancy. However, because of altered pharmacokinetics (increased volume of distribution, renal clearance), clinicians should titrate to effect and monitor for toxicity. Avoid high-dose aspirin in third trimester due to fetal risks. Propoxyphene clearance may be increased in pregnancy, but no standard dose change recommended; use minimal effective dose.
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 with ASA contains propoxyphene and aspirin. Propoxyphene has been withdrawn from the US market due to cardiotoxicity (QT prolongation, risk of fatal arrhythmias). Use is not recommended; consider alternatives. Aspirin component increases bleeding risk, especially with concurrent anticoagulants. Avoid in children with viral illness due to Reye's syndrome risk.
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 take more than prescribed as overdose can cause serious heart problems or death.,Avoid alcohol while taking this medication as it increases risk of liver damage and bleeding.,Aspirin may increase risk of bleeding; report unusual bruising or bleeding to your doctor.,If you have asthma, nasal polyps, or allergies, aspirin may cause severe allergic reactions.,Do not use in children or teenagers with chickenpox or flu-like symptoms due to risk of Reye's syndrome.,This medicine may cause drowsiness or dizziness; avoid driving until you know how it affects you.
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 W/ ASA vs ANEXSIA 5/325, answered by our medical review team.
DARVON W/ ASA is a Opioid Analgesic Combination that works by Combination analgesic: propoxyphene is a weak opioid agonist binding to mu-opioid receptors, inhibiting ascending pain pathways; aspirin irreversibly inhibits cyclooxygenase-1 and -2, reducing prostaglandin synthesis.. 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 W/ ASA 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 W/ ASA is: 1 capsule (propoxyphene HCl 65 mg / aspirin 650 mg) orally every 4 hours as needed for pain, not to exceed 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 W/ ASA 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 W/ ASA is classified as Category C. First trimester: Aspirin component associated with increased risk of neural tube defects and gastroschisis. Propoxyphene not associated with major malformations but data limited. S. 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.