Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PERCODAN 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
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia. Oxycodone acts on the central nervous system (CNS) to produce analgesia. Aspirin inhibits cyclooxygenase, leading to decreased prostaglandin synthesis, which reduces pain and inflammation.
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.
Moderate to moderately severe pain,Off-label: Severe pain unresponsive to non-opioid analgesics
Management of moderate to moderately severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate
1-2 tablets orally every 4-6 hours as needed for pain. Each tablet contains oxycodone 4.5 mg and aspirin 325 mg.
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).
Oxycodone: 3-5 hours, prolonged in elderly, hepatic/renal impairment. Aspirin: 2-3 hours at low doses; 15-30 hours at anti-inflammatory doses due to saturable metabolism.
Hydrocodone: 3.8-4.5 hours (immediate-release). Acetaminophen: 2-3 hours. Clinical note: Half-life prolonged in hepatic impairment; requires dose adjustment.
Oxycodone is metabolized primarily via CYP3A4 to noroxycodone and via CYP2D6 to oxymorphone, a more potent analgesic. Aspirin is hydrolyzed to salicylate, which is further conjugated with glycine (forming salicyluric acid) and glucuronic acid.
Hydrocodone: CYP3A4 and CYP2D6; Acetaminophen: primarily via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1.
Oxycodone: primarily renal (65-87% as parent and metabolites, mostly noroxycodone and oxymorphone conjugates); ~10% fecal. Aspirin: renal (75-90% as salicylates and metabolites, dose-dependent).
Renal: ~90-100% as hydrocodone metabolites (conjugated) and unchanged hydrocodone; ~60% as acetaminophen metabolites (glucuronide, sulfate, cysteine); <5% unchanged acetaminophen. Biliary/fecal: <5%.
Oxycodone: 38-45% bound to albumin. Aspirin: 80-90% bound to albumin (saturable).
Hydrocodone: ~20-30% (albumin). Acetaminophen: ~10-25% (albumin).
Oxycodone: 2.0-3.5 L/kg, extensive tissue distribution. Aspirin: 0.15-0.2 L/kg (low Vd).
Hydrocodone: 3-4 L/kg (extensive tissue distribution). Acetaminophen: ~1 L/kg (uniformly distributed).
Oxycodone: oral 60-87% (first-pass metabolism). Aspirin: oral 50-75% (dose-dependent; hydrolyzed to salicylate).
Oral: Hydrocodone ~70% (high first-pass metabolism); Acetaminophen ~85-90% (minimal first-pass).
Avoid use if GFR < 30 m L/min. For GFR 30-60 m L/min: reduce dose or extend interval; consider alternative therapy due to aspirin component.
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 severe hepatic impairment (Child-Pugh C). In moderate impairment (Child-Pugh B): reduce dose by 50% and monitor. In mild impairment (Child-Pugh A): use with caution.
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 < 12 years. For children ≥ 12 years: 1 tablet orally every 4-6 hours as needed; maximum 4 tablets/day.
Not recommended for pediatric patients; safety and efficacy not established for children under 18 years. For adolescents ≥18 years: adult dosing.
Start with 1 tablet orally every 6 hours; titrate cautiously due to increased sensitivity to oxycodone and risk of aspirin-induced GI bleeding. Monitor renal function.
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.
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM IN CYP2D6 POOR METABOLIZERS; NEONATAL OPIOID WITHDRAWAL SYNDROME; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and INTERACTION WITH ALCOHOL.
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, especially in elderly or debilitated patients,Risk of opioid-induced hyperalgesia,Adrenal insufficiency with prolonged use,Severe hypotension,Gastrointestinal obstruction or severe constipation,Seizures in patients with seizure disorders,Serotonin syndrome with serotonergic drugs,Reye syndrome in children with viral illnesses (due to aspirin)
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 oxycodone, aspirin, or any component,Significant respiratory depression,Acute or severe bronchial asthma,Paralytic ileus,Suspected surgical abdomen,Severe bleeding disorders,Children with viral illness (aspirin risk of Reye syndrome),Concomitant use with MAO inhibitors or within 14 days of discontinuation
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. Grapefruit and grapefruit juice may increase oxycodone levels, enhancing side effects; avoid concurrent consumption. Aspirin component may cause gastrointestinal irritation; take with food or milk to reduce upset. Do not consume high-dose vitamin C or other acidifying agents as they may increase aspirin absorption and risk of salicylate toxicity.
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.
Percodan (oxycodone/aspirin) is contraindicated in pregnancy. Aspirin is associated with premature ductus arteriosus closure and oligohydramnios in third trimester; risk of premature closure increases with gestational age. Oxycodone use in first trimester may increase risk of congenital malformations (neural tube defects, cardiac defects). Chronic use in third trimester may cause neonatal opioid withdrawal syndrome. Avoid in all trimesters unless clear benefit outweighs risks.
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.
Breastfeeding safety: oxycodone is excreted into breast milk (M/P ratio approximately 3.4:1). Aspirin is also excreted. Potential for infant opioid toxicity and Reye's syndrome. Use is not recommended; if essential, monitor infant for sedation, respiratory depression, and poor feeding.
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.
Pharmacokinetic changes in pregnancy: increased clearance of oxycodone due to enhanced hepatic metabolism and increased renal blood flow, requiring potentially higher doses to achieve analgesia. However, due to significant fetal risks, avoidance is preferable. If unavoidable, dose adjustment should be individualized, typically a 20-30% increase in opioid requirement may be needed. Aspirin dose unchanged but risk of bleeding and premature ductus closure limits use.
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.
PERCODAN contains oxycodone and aspirin. Use with caution in patients with bleeding disorders or those on anticoagulants due to aspirin's antiplatelet effect. Monitor for respiratory depression, especially in elderly or opioid-naive patients. Avoid in children and adolescents with viral infections due to Reye's syndrome risk from aspirin. The oxycodone component may cause histamine release leading to pruritus; consider antihistamine co-prescription. Taper dose to avoid withdrawal symptoms upon discontinuation.
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.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Avoid alcohol and other central nervous system depressants (sedatives, tranquilizers) as they may cause dangerous drowsiness or slowed breathing.,Do not drive or operate heavy machinery until you know how this medication affects you.,Aspirin in this medication increases bleeding risk; avoid other NSAIDs or anticoagulants unless approved by your doctor.,Seek emergency care if you experience signs of allergic reaction (rash, swelling, difficulty breathing) or signs of bleeding (unusual bruising, black/tarry stools).,Do not crush or chew tablets; swallow whole to avoid rapid release of oxycodone.,Store securely away from children and pets; dispose of unused medication properly via drug take-back programs.,Do not stop suddenly without medical guidance to avoid withdrawal symptoms (anxiety, sweating, nausea, muscle aches).
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 PERCODAN vs ANEXSIA 7.5/325, answered by our medical review team.
PERCODAN is a Opioid Analgesic Combination that works by Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia. Oxycodone acts on the central nervous system (CNS) to produce analgesia. Aspirin inhibits cyclooxygenase, leading to decreased prostaglandin synthesis, which reduces pain and inflammation.. 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 PERCODAN 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 PERCODAN is: 1-2 tablets orally every 4-6 hours as needed for pain. Each tablet contains oxycodone 4.5 mg and aspirin 325 mg.. 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 PERCODAN 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. PERCODAN is classified as Category C. Percodan (oxycodone/aspirin) is contraindicated in pregnancy. Aspirin is associated with premature ductus arteriosus closure and oligohydramnios in third trimester; risk of prematu. 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.