Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PERCODAN vs ANEXSIA 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 semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.
Moderate to moderately severe pain,Off-label: Severe pain unresponsive to non-opioid analgesics
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
1-2 tablets orally every 4-6 hours as needed for pain. Each tablet contains oxycodone 4.5 mg and aspirin 325 mg.
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
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.
Oxycodone: terminal half-life 3.2-4.3 hours (immediate-release); prolonged in hepatic impairment. Acetaminophen: terminal half-life 2-3 hours (therapeutic doses); prolonged in hepatic impairment or overdose.
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: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (hydromorphone). Acetaminophen: hepatic metabolism via conjugation (glucuronidation, sulfation) and CYP2E1-mediated oxidation to toxic NAPQI.
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).
Oxycodone: renal excretion of metabolites (conjugated and unconjugated) and parent drug; ~10% excreted unchanged. Acetaminophen: renal excretion of metabolites (glucuronide and sulfate conjugates); ~2-4% excreted unchanged.
Oxycodone: 38-45% bound to albumin. Aspirin: 80-90% bound to albumin (saturable).
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
Oxycodone: 2.0-3.5 L/kg, extensive tissue distribution. Aspirin: 0.15-0.2 L/kg (low Vd).
Oxycodone: Vd 2.0-3.0 L/kg; distributes extensively into tissues. Acetaminophen: Vd 0.8-1.0 L/kg; relatively uniform distribution.
Oxycodone: oral 60-87% (first-pass metabolism). Aspirin: oral 50-75% (dose-dependent; hydrolyzed to salicylate).
Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses).
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.
GFR 30-50 m L/min: use with caution, increase dosing interval to every 6 hours; GFR <30 m L/min: avoid use due to hydrocodeone accumulation.
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 A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
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 children under 18 years due to risk of respiratory depression.
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.
Start with lowest dose (1 tablet every 6 hours), monitor renal and hepatic function, and avoid in frail elderly due to increased fall and cognitive impairment risk.
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.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and hepatotoxicity from acetaminophen overdose.
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 with benzodiazepines or other CNS depressants; hepatotoxicity; adrenal insufficiency; severe hypotension; gastrointestinal obstruction; seizure; and serotonin syndrome.
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
Hypersensitivity to hydrocodone or acetaminophen; significant respiratory depression; acute or severe bronchial asthma; GI obstruction; known or suspected paralytic ileus; severe hepatic impairment; and concurrent use of MAOIs within 14 days.
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. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
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.
First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal renal toxicity, oligohydramnios, and premature closure of ductus arteriosus. Use only if clearly needed.
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.
Paracetamol and hydrocodone are excreted in breast milk. M/P ratio: paracetamol ~1.0, hydrocodone ~1.0-2.0. Use with caution; monitor infant for drowsiness and respiratory depression. Consider risk of infant sedation with long-term use.
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 in pregnancy may require dose adjustment. Monitor for pain control and adverse effects; no fixed dose change recommended. Consider lower starting dose due to potential fetal risks. Avoid chronic use; taper if possible.
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 5/325 contains hydrocodone 5 mg and acetaminophen 325 mg. Maximum acetaminophen dose from all sources should not exceed 4 g/day in adults; avoid in severe hepatic impairment. Hydrocodone is a Schedule II controlled substance with abuse potential; monitor for respiratory depression, especially in opioid-naive patients. Use with caution in patients with COPD, sleep apnea, or increased intracranial pressure. Consider naloxone co-prescription for high-risk patients. For acute pain, limit duration to 3-7 days.
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).
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Do not consume alcohol or other sedatives (e.g., benzodiazepines) while taking this medication.,Avoid other products containing acetaminophen (e.g., Tylenol, cold remedies) to prevent liver damage.,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 others; dispose of unused medication via drug take-back programs.,Seek emergency help if you have trouble breathing, severe drowsiness, or signs of allergic reaction.
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 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 5/325 is a Opioid Analgesic Combination that works by Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between PERCODAN and ANEXSIA 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 5/325 is: 1-2 tablets 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 PERCODAN and ANEXSIA 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 5/325 is classified as Category C. First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal re. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.