Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DARVON COMPOUND 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
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 mu-opioid receptor agonist, producing analgesia and euphoria. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.
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 treatment with an opioid is appropriate and for which alternative treatments are inadequate
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 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: 6-12 hours (terminal, prolonged in overdose due to enterohepatic recirculation). Acetaminophen: 2-3 hours (terminal). Clinical context: accumulation in elderly, hepatic impairment.
Hydrocodone: 3.8-4.5 hours (immediate-release). Acetaminophen: 2-3 hours. Clinical note: Half-life prolonged in hepatic impairment; requires dose adjustment.
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: CYP3A4 and CYP2D6; Acetaminophen: primarily via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1.
Renal: ~70% as unchanged drug and glucuronide conjugates (propoxyphene and acetaminophen). Fecal: <10% as unchanged and metabolites. Biliary: minor route for propoxyphene 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: ~80% (albumin). Acetaminophen: 10-25% (albumin; lower at toxic concentrations).
Hydrocodone: ~20-30% (albumin). Acetaminophen: ~10-25% (albumin).
Propoxyphene: 0.9-1.2 L/kg (wide distribution, high tissue binding). Acetaminophen: 0.8-1.0 L/kg (uniform distribution).
Hydrocodone: 3-4 L/kg (extensive tissue distribution). Acetaminophen: ~1 L/kg (uniformly distributed).
Propoxyphene: 30-70% (first-pass metabolism, dose-dependent; higher with food). Acetaminophen: 60-90% (oral, variable first-pass; >95% for rectal? Not applicable here).
Oral: Hydrocodone ~70% (high first-pass metabolism); Acetaminophen ~85-90% (minimal first-pass).
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.
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 A or B: reduce dose by 50% (max 3 capsules/day) and monitor for sedation and respiratory depression.
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 pediatric patients due to risk of propoxyphene cardiotoxicity and aspirin-associated Reye's syndrome in viral illness.
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/day. Avoid in patients >80 years due to increased risk of CNS depression, falls, and bleeding from aspirin.
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 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.
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 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 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, 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.
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, 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 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.
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.
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.
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.
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.
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 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 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 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 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.
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 COMPOUND vs ANEXSIA 7.5/325, 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 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 COMPOUND 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 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 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 COMPOUND 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 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 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.