Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PERCOCET 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 mu-opioid receptor agonist, inhibiting ascending pain pathways and altering pain perception and emotional response. Acetaminophen inhibits cyclooxygenase (COX) in the CNS, reducing prostaglandin synthesis and exerting analgesic and antipyretic effects.
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.
Management of moderate to moderately severe pain (FDA-approved),Off-label: severe pain when other analgesics are inadequate (individualized use)
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
One tablet (5 mg oxycodone/325 mg acetaminophen) every 6 hours as needed for pain; maximum 12 tablets per day.
1-2 tablets orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Oxycodone: 3.5–4.5 hours (terminal) in normal renal function; prolonged in hepatic/renal impairment (up to 6–12 hours). Acetaminophen: 2–3 hours (terminal) in overdose, extended with hepatic injury.
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: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (noroxycodone, oxymorphone). Acetaminophen: hepatic via glucuronidation (UGT1A1/1A6), sulfation, and minor CYP2E1 oxidation.
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 (up to 19% as unchanged drug, 50% as noroxycodone and oxymorphone metabolites); about 10% biliary/fecal. Acetaminophen: renal (majority as glucuronide and sulfate conjugates, about 5% unchanged).
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 and alpha-1-acid glycoprotein. Acetaminophen: 10–25% bound to albumin (minimal).
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
Oxycodone: Vd approximately 2.6 L/kg (extensive tissue distribution). Acetaminophen: Vd approximately 0.9 L/kg (total body water).
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 bioavailability 60–87% (immediate-release). Acetaminophen: oral bioavailability 85–98% (first-pass metabolism minimal).
Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses).
GFR >60 m L/min: no adjustment; GFR 30-60 m L/min: dose every 8 hours; GFR <30 m L/min: avoid use or use with extreme caution, consider reducing dose to 50% or extending interval to every 12 hours; not recommended in ESRD.
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.
Child-Pugh A: no adjustment; Child-Pugh B: reduce total daily dose by 50%; Child-Pugh C: avoid use.
Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
Not FDA-approved for children <18 years; off-label: 0.1-0.2 mg/kg oxycodone (max 5 mg) plus 5-10 mg/kg acetaminophen every 4-6 hours; total acetaminophen not to exceed 75 mg/kg/day or 4 g/day.
Not recommended for children under 18 years due to risk of respiratory depression.
Start with low end of dosing, e.g., 2.5 mg oxycodone/325 mg acetaminophen every 6 hours; monitor renal function and avoid >4 g/day acetaminophen; titrate cautiously due to increased sensitivity and fall risk.
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.
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of any dosage (especially in children) can be fatal; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; CYP3A4 inhibitors or discontinuation of CYP3A4 inducers may cause fatal respiratory depression; concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death.
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.
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; severe hypotension; seizures; serotonin syndrome; adrenal insufficiency; hepatotoxicity (acetaminophen); increased risk of pancreatitis (if combined with alcohol); risk of overuse for acetaminophen.
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, acetaminophen, or any component; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; severe hepatic impairment (acetaminophen hepatotoxicity risk).
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 and grapefruit juice. Alcohol can potentiate hepatotoxicity from acetaminophen and CNS depression from oxycodone. Grapefruit juice may increase oxycodone levels, enhancing sedative and respiratory depressant effects. No other significant food interactions.
Avoid alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
Percocet (oxycodone/acetaminophen) is pregnancy category C prior to 30 weeks gestation and category D after 30 weeks. First trimester: No clear evidence of major malformations, but opioid use may be associated with neural tube defects and gastroschisis. Second trimester: Risk of miscarriage, intrauterine growth restriction. Third trimester: Prolonged use can cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. Acetaminophen is considered safe in therapeutic doses but overdose is hepatotoxic to fetus.
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.
Oxycodone is excreted into breast milk; relative infant dose is approximately 1-2% of maternal weight-adjusted dose. M/P ratio (milk/plasma) is about 3.2:1 for oxycodone. Acetaminophen M/P ratio ~1.0. Low levels expected, but monitor infant for sedation and poor feeding. Caution with maternal high doses or prolonged use; avoid if mother is ultra-rapid CYP2D6 metabolizer due to risk of toxicity.
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.
During pregnancy, increased plasma volume and hepatic metabolism may require higher doses of oxycodone to achieve analgesic effect. However, due to fetal risks, use lowest effective dose for shortest duration. No specific dose adjustments are validated; clinical response should guide dosing. Acetaminophen dosing remains unchanged but avoid exceeding 3 g/day in pregnancy.
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.
Percocet contains oxycodone and acetaminophen; the acetaminophen component limits total daily dosing to avoid hepatotoxicity (max 4 g/day in adults, lower in liver disease or alcohol use). Due to oxycodone, it is a Schedule II controlled substance with high abuse potential. Constipation is a common adverse effect; consider prophylactic bowel regimen (e.g., docusate, senna). Respiratory depression risk is dose-related and increased with concurrent CNS depressants. Use with caution in elderly, renal impairment, or sleep apnea. Tolerance and dependence develop with prolonged use. Taper to discontinue after chronic use. Avoid in patients with known hypersensitivity to opioids or acetaminophen.
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 sedatives (e.g., benzodiazepines, muscle relaxants) as they increase risk of severe drowsiness and respiratory depression.,Do not drive or operate heavy machinery until you know how this medication affects you; it may cause dizziness or drowsiness.,Do not exceed 4,000 mg of acetaminophen per day from all sources; check over-the-counter medications for acetaminophen content.,Stop taking and seek immediate medical attention if you experience symptoms of liver damage: yellowing of skin/eyes, dark urine, abdominal pain.,Common side effects include constipation, nausea, vomiting, and drowsiness. Increase fluid and fiber intake to prevent constipation.,This drug has a high risk of addiction and dependence. Store securely out of reach of others. Do not share with others.,Do not suddenly stop taking after prolonged use; a gradual taper is needed to avoid withdrawal symptoms.,Contact your doctor if pain is not controlled or if you experience signs of allergic reaction (rash, swelling, trouble breathing).
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 PERCOCET vs ANEXSIA 5/325, answered by our medical review team.
PERCOCET is a Opioid Analgesic Combination that works by Oxycodone is a mu-opioid receptor agonist, inhibiting ascending pain pathways and altering pain perception and emotional response. Acetaminophen inhibits cyclooxygenase (COX) in the CNS, reducing prostaglandin synthesis and exerting analgesic and antipyretic effects.. 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 PERCOCET 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 PERCOCET is: One tablet (5 mg oxycodone/325 mg acetaminophen) every 6 hours as needed for pain; maximum 12 tablets per day.. 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 PERCOCET 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. PERCOCET is classified as Category C. Percocet (oxycodone/acetaminophen) is pregnancy category C prior to 30 weeks gestation and category D after 30 weeks. First trimester: No clear evidence of major malformations, but. 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.