Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
PERCOCET 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
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.
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.
Management of moderate to moderately severe pain (FDA-approved),Off-label: severe pain when other analgesics are inadequate (individualized use)
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.
One tablet (5 mg oxycodone/325 mg acetaminophen) every 6 hours as needed for pain; maximum 12 tablets 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.
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.
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
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-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).
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).
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Oxycodone: 38–45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10–25% bound to albumin (minimal).
<20%; primarily binds to albumin.
Oxycodone: Vd approximately 2.6 L/kg (extensive tissue distribution). Acetaminophen: Vd approximately 0.9 L/kg (total body water).
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Oxycodone: oral bioavailability 60–87% (immediate-release). Acetaminophen: oral bioavailability 85–98% (first-pass metabolism minimal).
Oral: 85–95%; rectal: 70–80%.
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 30-59 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.
Child-Pugh A: no adjustment; Child-Pugh B: reduce total daily dose by 50%; Child-Pugh C: avoid use.
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 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.
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.
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 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.
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; 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.
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.
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 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, 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 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 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.
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: 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.
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.
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.
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.
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.
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.
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.
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.,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 PERCOCET vs CO-GESIC, 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.. 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 PERCOCET 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 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 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 PERCOCET 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. 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. 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.