Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PERCODAN vs ANEXSIA 7.5/650
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 that inhibits ascending pain pathways and alters pain perception; acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and fever.
Moderate to moderately severe pain,Off-label: Severe pain unresponsive to non-opioid analgesics
Management of acute pain severe enough to require an opioid analgesic 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 orally every 4 to 6 hours as needed; maximum 6 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.
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.
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 liver glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3), with minor CYP2E1 oxidation.
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).
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.
Oxycodone: 38-45% bound to albumin. Aspirin: 80-90% bound to albumin (saturable).
Hydrocodone: ~36% bound to serum proteins. Acetaminophen: 10-25% bound (minimal binding).
Oxycodone: 2.0-3.5 L/kg, extensive tissue distribution. Aspirin: 0.15-0.2 L/kg (low Vd).
Hydrocodone: Vd ~3-5 L/kg (wide distribution). Acetaminophen: Vd ~0.9-1.0 L/kg (primarily body water).
Oxycodone: oral 60-87% (first-pass metabolism). Aspirin: oral 50-75% (dose-dependent; hydrolyzed to salicylate).
Oral: Hydrocodone ~70-80% (variable first-pass). Acetaminophen ~63-89% (mean 75-80%).
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.
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 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; Child-Pugh Class B: reduce dose by 50% and monitor; Child-Pugh Class C: contraindicated due to hydrocodone.
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 in pediatric patients due to risk of respiratory depression; for ages <18, contraindicated.
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 with lowest effective dose, monitor for respiratory depression and constipation; maximum 4 tablets per day in patients >65 years.
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 (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 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)
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 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 (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. 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 due to increased risk of acetaminophen hepatotoxicity and additive CNS depression. Grapefruit juice may increase hydrocodone absorption; consider avoiding. No other significant food interactions.
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. 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.
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.
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.
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 oxycodone in pregnancy may require increased dose; acetaminophen pharmacokinetics unchanged. Adjust based on pain control and withdrawal risk.
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.
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.
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.,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 PERCODAN vs ANEXSIA 7.5/650, 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 7.5/650 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 PERCODAN 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 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 7.5/650 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 PERCODAN 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. 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 7.5/650 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.