Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DARVON COMPOUND vs ANEXSIA 7.5/650
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 that inhibits ascending pain pathways and alters pain perception; acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and fever.
Management of mild to moderate pain,As an antipyretic (aspirin component),Off-label: Not commonly used due to safety concerns
Management of acute pain severe enough to require an opioid analgesic 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 orally every 4 to 6 hours as needed; maximum 6 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.
Hydrocodone: Terminal half-life 3.8-7.2 hours (mean 5.6 h). Acetaminophen: 1.5-2.5 hours (therapeutic) but prolonged to >4 hours in overdose with hepatotoxicity risk.
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 liver glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3), with minor CYP2E1 oxidation.
Renal: ~70% as unchanged drug and glucuronide conjugates (propoxyphene and acetaminophen). Fecal: <10% as unchanged and metabolites. Biliary: minor route for propoxyphene conjugates.
Hydrocodone: Renal elimination of metabolites (hydromorphone, norhydrocodone) and unchanged drug accounts for ~60-90% of clearance. Acetaminophen: ~85% of dose is excreted in urine as glucuronide and sulfate conjugates; 5-10% unchanged; 2-5% as mercapturate.
Propoxyphene: ~80% (albumin). Acetaminophen: 10-25% (albumin; lower at toxic concentrations).
Hydrocodone: ~36% bound to serum proteins. Acetaminophen: 10-25% bound (minimal binding).
Propoxyphene: 0.9-1.2 L/kg (wide distribution, high tissue binding). Acetaminophen: 0.8-1.0 L/kg (uniform distribution).
Hydrocodone: Vd ~3-5 L/kg (wide distribution). Acetaminophen: Vd ~0.9-1.0 L/kg (primarily body water).
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 ~70-80% (variable first-pass). Acetaminophen ~63-89% (mean 75-80%).
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.
Cr Cl <30 m L/min: contraindicated; Cr Cl 30-60 m L/min: maximum 3 tablets per day; given the hydrocodone component, avoid in severe renal impairment.
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; Child-Pugh Class B: reduce dose by 50% and monitor; Child-Pugh Class C: contraindicated due to hydrocodone.
Not recommended for pediatric patients due to risk of propoxyphene cardiotoxicity and aspirin-associated Reye's syndrome in viral illness.
Not recommended in pediatric patients due to risk of respiratory depression; for ages <18, contraindicated.
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 with lowest effective dose, monitor for respiratory depression and constipation; maximum 4 tablets per day in patients >65 years.
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 (especially in children) can be fatal; neonatal opioid withdrawal syndrome; cytochrome P450 3A4 interaction (concomitant use with CYP3A4 inhibitors may increase hydrocodone levels); risk of medication errors (confusion between different strengths).
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.
Addiction, abuse, and misuse; respiratory depression; neonatal opioid withdrawal syndrome; interactions with CNS depressants; risk of serotonin syndrome with serotonergic drugs; adrenal insufficiency; hypotension; seizures; gastrointestinal obstruction; severe cutaneous reactions (acetaminophen); hepatotoxicity (acetaminophen overdose); acute abdominal conditions; impaired mental/physical abilities; elderly/debilitated patients; renal/hepatic impairment.
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 (without monitoring or resuscitative equipment); known or suspected gastrointestinal obstruction (including paralytic ileus); hypersensitivity to hydrocodone or acetaminophen; use with 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 due to increased risk of acetaminophen hepatotoxicity and additive CNS depression. Grapefruit juice may increase hydrocodone absorption; consider avoiding. No other significant food interactions.
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. First trimester: Possible increased risk of cardiac defects with oxycodone. Second/third trimester: Chronic use may lead to neonatal opioid withdrawal syndrome; no clear teratogenicity. Acetaminophen is generally safe, but high doses may be hepatotoxic.
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.
Oxycodone: M/P ratio ~0.8-3; present in milk; risk of neonatal sedation. Acetaminophen: M/P ~0.8-1, low risk. Avoid due to oxycodone; consider alternative analgesic.
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 oxycodone in pregnancy may require increased dose; acetaminophen pharmacokinetics unchanged. Adjust based on pain control and withdrawal risk.
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.
Fixed-dose combination of hydrocodone bitartrate (7.5 mg) and acetaminophen (650 mg). Hydrocodone is a schedule II controlled substance with high abuse potential. Acetaminophen hepatotoxicity risk increases above 3 g/day; prescribe no more than 4 doses per day. Monitor for respiratory depression, especially in opioid-naïve patients. Avoid in severe hepatic impairment. Use with caution in patients with COPD, sleep apnea, or concurrent CNS depressants. Consider naloxone co-prescription if high opioid dose or concurrent benzodiazepine use.
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.,Do not take with alcohol or other medications containing acetaminophen.,May cause drowsiness or dizziness; avoid driving or operating machinery until effects are known.,Store securely out of reach of children and others; dispose of unused tablets properly.,Seek emergency care for difficulty breathing, severe sedation, or signs of allergic reaction.,Do not abruptly stop after prolonged use; withdrawal symptoms may occur.
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 7.5/650, 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 7.5/650 is a Opioid Analgesic Combination that works by Hydrocodone is a mu-opioid receptor agonist that inhibits ascending pain pathways and alters pain perception; acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and fever.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DARVON COMPOUND and ANEXSIA 7.5/650 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 7.5/650 is: 1 tablet orally every 4 to 6 hours as needed; maximum 6 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 7.5/650 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 7.5/650 is classified as Category C. FDA Category C. First trimester: Possible increased risk of cardiac defects with oxycodone. Second/third trimester: Chronic use may lead to neonatal opioid withdrawal syndrome; no . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.