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 7.5/325
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 mu-opioid receptor agonist, producing analgesia and euphoria. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.
Mild to moderate pain,Pain accompanied by inflammation or fever
Management of moderate to moderately severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate
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 tablet (hydrocodone 7.5 mg / acetaminophen 325 mg) orally every 4 to 6 hours as needed for pain; maximum 6 tablets per day (hydrocodone 45 mg / acetaminophen 1950 mg).
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.
Hydrocodone: 3.8-4.5 hours (immediate-release). Acetaminophen: 2-3 hours. Clinical note: Half-life prolonged in hepatic impairment; requires dose adjustment.
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: CYP3A4 and CYP2D6; Acetaminophen: primarily via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1.
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.
Renal: ~90-100% as hydrocodone metabolites (conjugated) and unchanged hydrocodone; ~60% as acetaminophen metabolites (glucuronide, sulfate, cysteine); <5% unchanged acetaminophen. Biliary/fecal: <5%.
Propoxyphene is 70–80% bound to albumin; aspirin is 50–80% bound to albumin (dose-dependent due to saturable binding).
Hydrocodone: ~20-30% (albumin). Acetaminophen: ~10-25% (albumin).
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.
Hydrocodone: 3-4 L/kg (extensive tissue distribution). Acetaminophen: ~1 L/kg (uniformly distributed).
Propoxyphene: 30–70% oral bioavailability due to first-pass metabolism; aspirin: 50–70% oral bioavailability (first-pass hydrolysis to salicylate).
Oral: Hydrocodone ~70% (high first-pass metabolism); Acetaminophen ~85-90% (minimal first-pass).
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).
For GFR 30-59 m L/min: administer every 6 hours; maximum 4 tablets per day. For GFR 15-29 m L/min: administer every 8 hours; maximum 3 tablets per day. For GFR <15 m L/min: not recommended due to accumulation of metabolites.
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 Class A: no adjustment necessary. Child-Pugh Class B: reduce dose by 25-50% and extend dosing interval to every 6-8 hours; maximum 4 tablets per day. Child-Pugh Class C: contraindicated due to risk of hepatotoxicity.
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 pediatric patients; safety and efficacy not established for children under 18 years. For adolescents ≥18 years: adult dosing.
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.
Initiate at 1 tablet (hydrocodone 5 mg / acetaminophen 325 mg) every 6 hours as needed; titrate cautiously due to increased sensitivity, decreased renal function, and risk of respiratory depression. Maximum 4 tablets per day.
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.
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 due to acetaminophen.
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 of alcohol, benzodiazepines, or other CNS depressants; hepatotoxicity; severe hypotension; adrenal insufficiency; seizures; GI obstruction; impaired mental/physical abilities; use in elderly, cachectic, or debilitated patients; renal impairment; hepatic impairment; pregnancy; labor and delivery; nursing mothers; pediatric use; driving and operating machinery.
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.
Significant respiratory depression; acute or severe bronchial asthma; known or suspected GI obstruction; hypersensitivity to hydrocodone or acetaminophen; concomitant use of MAOIs or within 14 days of such therapy.
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 consumption due to increased risk of acetaminophen hepatotoxicity and CNS depression. No specific food restrictions, but grapefruit juice may theoretically affect hydrocodone metabolism via CYP3A4 inhibition; however, clinical significance is uncertain.
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.
FDA Category C (hydrocodone) and Category D (acetaminophen) in third trimester. First trimester: Acetaminophen associated with rare gastroschisis; hydrocodone risk of neural tube defects. Second trimester: No major malformations except with prolonged opioid use. Third trimester: Acetaminophen safe; hydrocodone risk of neonatal opioid withdrawal syndrome (NOWS). Avoid near term.
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.
Hydrocodone/acetaminophen excreted in breast milk. M/P ratio unknown. Hydrocodone relative infant dose <3% of weight-adjusted maternal dose. Acetaminophen relative infant dose <2%. Use with caution; monitor infant for sedation, apnea, poor feeding. Highest risk in CYP2D6 ultrarapid metabolizers.
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 of hydrocodone in pregnancy may require dose adjustment; monitor for inadequate analgesia. Acetaminophen pharmacokinetics unchanged. Avoid high doses (hepatotoxicity risk). Consider baseline hepatic function. No specific dose adjustment recommended; titrate to effect.
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 7.5/325 (hydrocodone/acetaminophen) carries a boxed warning for acetaminophen hepatotoxicity; maximum acetaminophen dose from all sources should not exceed 4 g/day. Hydrocodone is metabolized by CYP2D6 to hydromorphone; ultrarapid metabolizers may experience toxicity. Avoid concurrent use with other CNS depressants including alcohol. Prescribe with caution in patients with renal impairment (hydrocodone accumulation) or hepatic impairment (acetaminophen toxicity). Monitor for signs of respiratory depression, especially at therapy initiation and dose titration. Use the lowest effective dose for the shortest duration.
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.
Do not exceed 6 tablets per day due to acetaminophen content.,Avoid alcohol while taking this medication.,Do not drive or operate heavy machinery until you know how this medication affects you.,Take exactly as prescribed; do not share with others.,Seek emergency help if you experience difficulty breathing, severe drowsiness, or signs of allergic reaction.,Store securely out of reach of children and dispose of unused medication properly.
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 7.5/325, 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 7.5/325 is a Opioid Analgesic Combination that works by Hydrocodone is a mu-opioid receptor agonist, producing analgesia and euphoria. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DARVON W/ ASA and ANEXSIA 7.5/325 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 7.5/325 is: 1 tablet (hydrocodone 7.5 mg / acetaminophen 325 mg) orally every 4 to 6 hours as needed for pain; maximum 6 tablets per day (hydrocodone 45 mg / acetaminophen 1950 mg).. 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 7.5/325 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 7.5/325 is classified as Category C. FDA Category C (hydrocodone) and Category D (acetaminophen) in third trimester. First trimester: Acetaminophen associated with rare gastroschisis; hydrocodone risk of neural tube d. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.