Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
OXYCET 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 full opioid agonist with relative selectivity for the mu-opioid receptor, though it can interact with other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Acetaminophen is believed to produce analgesia through central action, possibly mediated through inhibition of cyclooxygenase (COX) and activation of descending serotonergic pathways, though the exact mechanism is not fully understood.
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 where an opioid analgesic is appropriate,Off-label use: Relief of pain in various conditions including postoperative pain, traumatic pain, and chronic pain
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.
1 tablet (325 mg acetaminophen and 5 mg oxycodone) orally every 4 to 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.
The terminal elimination half-life of oxycodone is approximately 3.5-4 hours for immediate-release formulations. For controlled-release formulations, the half-life is similar due to absorption-limited elimination, but the duration of action is extended due to the formulation. In elderly patients or those with hepatic impairment, half-life may be increased up to 2-fold.
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Oxycodone is extensively metabolized in the liver via cytochrome P450 3A4 (CYP3A4) and CYP2D6 to noroxycodone, oxymorphone, and noroxymorphone. Acetaminophen is primarily metabolized in the liver via conjugation (glucuronidation and sulfation) and, to a lesser extent, via CYP2E1 to a toxic metabolite (NAPQI) which is normally detoxified by glutathione.
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 is primarily metabolized in the liver via CYP3A4 to noroxycodone and via CYP2D6 to oxymorphone. Renal excretion accounts for approximately 87% of the administered dose, with 8.1% as unchanged oxycodone, 22.8% as noroxycodone, 9.1% as noroxymorphone, 3.2% as oxymorphone, and others. Fecal excretion is about 10%.
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Approximately 45% bound to plasma proteins, primarily albumin.
<20%; primarily binds to albumin.
Volume of distribution is 2.6-3.6 L/kg. This indicates extensive tissue distribution, with oxycodone widely distributed throughout body fluids and tissues, including the brain.
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Oral immediate-release: 60-87% due to first-pass metabolism. Extended-release: approximately the same as immediate-release when adjusted for dose. Intravenous: 100%. Rectal: similar to oral (60-87%).
Oral: 85–95%; rectal: 70–80%.
For Cr Cl 30-50 m L/min: administer every 6 hours; Cr Cl 10-29 m L/min: administer every 8 hours; Cr Cl < 10 m L/min: not recommended due to risk of oxycodone accumulation.
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 dose by 50% or extend dosing interval; Child-Pugh C: contraindicated or use with extreme caution, maximum 50% of normal dose.
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 recommended for children under 18 years due to risk of respiratory depression; for older adolescents (≥18 years), adult dosing may be considered.
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.
Initiate at lowest effective dose, typically one-half of adult dose (one tablet every 6 hours) and titrate slowly; caution due to increased sensitivity and risk of falls and respiratory depression.
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.
Addiction, Abuse, and Misuse: Oxycodone exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before prescribing, and monitor regularly for development of these behaviors or conditions. Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Accidental Ingestion: Accidental ingestion of even one dose of oxycodone, especially by children, can result in a fatal overdose of oxycodone. Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants may result in profound sedation, respiratory depression, coma, and death. Reserve for use in patients for whom alternative treatment options are inadequate. Hepatotoxicity: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses exceeding 4000 mg per day, and often involve more than one acetaminophen-containing product.
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.
Risk of addiction, abuse, and misuse,Life-threatening respiratory depression,Accidental ingestion (especially in children),Neonatal opioid withdrawal syndrome,Risks from concomitant use with benzodiazepines or other CNS depressants,Hepatotoxicity from acetaminophen,Severe hypotension,Gastrointestinal effects (e.g., constipation, ileus),Seizures in patients with seizure disorders,Serotonin syndrome with concomitant serotonergic drugs,Adrenal insufficiency,Use in patients with head injury or increased intracranial pressure,Use in patients with acute abdominal conditions
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 or acetaminophen,Significant respiratory depression,Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment,Paralytic ileus,Severe hepatic impairment (for acetaminophen component),Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy
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. Grapefruit juice may increase oxycodone levels (monitor for opioid effects); high-fat meals may delay absorption but not total exposure. No other significant dietary restrictions.
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.
Oxycodone/paracetamol (OXYCET). Oxycodone: FDA Category B (but Category D if prolonged use or near term). First trimester: Increased risk of neural tube defects, congenital heart defects; limited data, but avoid if possible. Second and third trimesters: Prolonged use may cause fetal dependence, withdrawal syndrome; near term, neonatal respiratory depression. Paracetamol: Category B; appears safe in standard doses but overdose causes fetal hepatotoxicity.
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 approximately 1.6-3.5% of maternal weight-adjusted dose. M/P ratio not firmly established. Use caution; monitor infant for sedation, respiratory depression, poor feeding. Paracetamol is safe; excreted in low levels. If prolonged maternal oxycodone use, risk of neonatal withdrawal.
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.
Oxycodone distribution volume increases in pregnancy; clearance may increase, potentially requiring higher doses to achieve analgesic efficacy, but no standard adjustment. Avoid chronic use; use lowest effective dose shortest duration. Paracetamol dose 650-1000 mg every 4-6 hours; max 4000 mg/day; no pregnancy-specific dose adjustment unless hepatic impairment.
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.
Oxycet is a combination of oxycodone and acetaminophen. Maximum acetaminophen daily dose is 4 g; in chronic alcohol use or hepatic impairment, limit to 2 g. Use with caution in elderly, respiratory compromise, or history of substance abuse. Constipation prophylaxis (e.g., stool softener) is recommended. Avoid concurrent use with other CNS depressants. Monitor for signs of tolerance, dependence, and misuse.
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 this medication exactly as prescribed. Do not increase dose or frequency without consulting your doctor.,Do not combine with other products containing acetaminophen (e.g., Tylenol) to avoid exceeding 4000 mg per day.,Avoid alcohol while taking this medication; it increases the risk of liver damage and sedation.,This drug can cause drowsiness or dizziness; do not drive or operate heavy machinery until you know how it affects you.,Constipation is common; increase fluid and fiber intake, and consider using a stool softener as recommended.,Do not stop taking suddenly; your doctor will guide you on tapering to prevent withdrawal symptoms.,Store securely out of reach of others; unused medication should be disposed of properly.
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 OXYCET vs CO-GESIC, answered by our medical review team.
OXYCET is a Opioid Analgesic Combination that works by Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, though it can interact with other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Acetaminophen is believed to produce analgesia through central action, possibly mediated through inhibition of cyclooxygenase (COX) and activation of descending serotonergic pathways, though the exact mechanism is not fully understood.. 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 OXYCET 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 OXYCET is: 1 tablet (325 mg acetaminophen and 5 mg oxycodone) orally every 4 to 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 OXYCET 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. OXYCET is classified as Category C. Oxycodone/paracetamol (OXYCET). Oxycodone: FDA Category B (but Category D if prolonged use or near term). First trimester: Increased risk of neural tube defects, congenital heart d. 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.