Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DARVON W/ ASA vs CO-GESIC
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.
CO-GESIC (hydrocodone/acetaminophen) is a combination analgesic. Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes in the CNS, reducing prostaglandin synthesis and elevating pain threshold.
Mild to moderate pain,Pain accompanied by inflammation or fever
FDA: Management of moderate to moderately severe pain where an opioid is appropriate.,Off-label: Not commonly used off-label; may be considered for refractory pain conditions.
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 (hydrocodone 5 mg/acetaminophen 500 mg per tablet) 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.
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
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-mediated N-demethylation to norhydrocodone (active) and O-demethylation via CYP2D6 to hydromorphone (active). Acetaminophen: hepatic via glucuronidation and sulfation; minor oxidation by CYP2E1 to NAPQI (toxic metabolite).
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.
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Propoxyphene is 70–80% bound to albumin; aspirin is 50–80% bound to albumin (dose-dependent due to saturable binding).
<20%; primarily binds to 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.
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Propoxyphene: 30–70% oral bioavailability due to first-pass metabolism; aspirin: 50–70% oral bioavailability (first-pass hydrolysis to salicylate).
Oral: 85–95%; rectal: 70–80%.
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 30-59 m L/min: Administer every 6 hours; GFR 10-29 m L/min: Administer every 8 hours; GFR <10 m L/min: Administer every 12 hours; avoid use in severe renal impairment.
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; Child-Pugh Class B: Reduce dose by 50% and extend interval to every 8 hours; Child-Pugh Class C: Use not recommended due to hepatotoxicity risk.
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.
Children ≥2 years: Hydrocodone 0.1-0.2 mg/kg/dose (max 5 mg/dose) plus acetaminophen 10-15 mg/kg/dose (max 500 mg/dose) orally every 4-6 hours as needed; maximum 5 doses per day.
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 at lower end of dosing range (e.g., 1 tablet every 6 hours) due to increased sensitivity to opioids and renal clearance decline; monitor for respiratory depression and sedation.
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; serious, life-threatening or fatal respiratory depression from opioid use; accidental ingestion of acetaminophen can cause acute liver failure; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks from concomitant use with benzodiazepines or other CNS depressants.
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.
Addiction, abuse, and misuse; respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risk with concomitant use of CNS depressants; severe hypotension; seizures; serotonin syndrome; adrenal insufficiency; hepatotoxicity (acetaminophen overdose); hypersensitivity reactions; constipation; urinary retention; impaired mental/physical abilities.
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, acetaminophen, or any component; significant respiratory depression; acute or severe bronchial asthma; known or suspected GI obstruction (e.g., paralytic ileus); use of MAO inhibitors (concurrent or 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 grapefruit and grapefruit juice as they may alter metabolism of hydrocodone. Take with food if gastrointestinal upset occurs. Avoid alcohol-containing foods or beverages. No other significant food interactions.
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: No adequate studies; risk cannot be ruled out. Second and third trimesters: Avoid prolonged use or high doses near term due to potential premature closure of ductus arteriosus and oligohydramnios.
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.
No data on M/P ratio; use with caution. Low molecular weight may be excreted into breast milk; monitor infant for sedation or respiratory depression.
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.
No specific dose adjustments required; however, due to increased renal clearance in pregnancy, shortened dosing intervals or higher doses may be needed for adequate analgesia. Monitor clinical response and adjust accordingly.
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.
Co-Gesic is a fixed-dose combination of hydrocodone and acetaminophen. Monitor for acetaminophen hepatotoxicity; maximum daily acetaminophen dose should not exceed 4 g. Hydrocodone is a Schedule II controlled substance with abuse potential. Use with caution in patients with respiratory compromise, COPD, or sleep apnea. Avoid concurrent use with other CNS depressants including alcohol. In opioid-tolerant patients, withdrawal may occur if discontinued abruptly.
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.,Avoid alcohol while taking this medication due to risk of liver damage and increased sedation.,Do not take other medications containing acetaminophen (Tylenol, many cold/flu products) to avoid exceeding the maximum daily dose (4 grams).,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 children and dispose of unused medication properly (take-back programs preferred).,Do not crush or chew extended-release formulations (if applicable).,Report signs of liver injury (yellowing skin/eyes, dark urine, abdominal pain) or respiratory depression (slow/shallow breathing) immediately.
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 CO-GESIC, 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.. CO-GESIC is a Opioid Analgesic Combination that works by CO-GESIC (hydrocodone/acetaminophen) is a combination analgesic. Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes in the CNS, reducing prostaglandin synthesis and elevating pain threshold.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DARVON W/ ASA and CO-GESIC 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 CO-GESIC is: 1-2 tablets (hydrocodone 5 mg/acetaminophen 500 mg per tablet) 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 CO-GESIC 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. CO-GESIC is classified as Category C. First trimester: No adequate studies; risk cannot be ruled out. Second and third trimesters: Avoid prolonged use or high doses near term due to potential premature closure of ductu. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.