Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ROXICET 5/500 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 that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and producing 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 where treatment with an opioid is appropriate and for which alternative treatments are inadequate
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.
1-2 tablets (5-10 mg oxycodone / 325-650 mg acetaminophen) orally every 4-6 hours as needed for pain; maximum 12 tablets per day (60 mg oxycodone / 6000 mg acetaminophen) in 24 hours.
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 hours (immediate-release); Acetaminophen: 2-3 hours. In hepatic impairment, oxycodone half-life prolonged (up to 12-15 hours).
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Oxycodone is metabolized primarily via CYP3A4 and CYP2D6 to noroxycodone and oxymorphone. Acetaminophen is metabolized mainly via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1 and CYP1A2 producing N-acetyl-p-benzoquinone imine (NAPQI).
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 hepatic metabolism to noroxycodone, oxymorphone, and conjugates; renal elimination of metabolites (about 60-87% as unchanged and metabolites), fecal < 10%. Acetaminophen: renal elimination of conjugates (90-100%), <5% unchanged.
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Oxycodone: ~45% bound to albumin; Acetaminophen: 10-25% bound to albumin.
<20%; primarily binds to albumin.
Oxycodone: 2-3 L/kg (extensive tissue distribution); Acetaminophen: 0.8-1.0 L/kg (distribution throughout body water).
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Oxycodone oral: 60-87% (high first-pass metabolism varies); Acetaminophen oral: 80-90%.
Oral: 85–95%; rectal: 70–80%.
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: use not recommended due to oxycodone accumulation; consider alternative.
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 Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and extend dosing interval to every 8 hours. Child-Pugh Class C: contraindicated due to acetaminophen hepatotoxicity.
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 typically recommended; use weight-based dosing of oxycodone 0.1-0.2 mg/kg/dose (max 5 mg/dose) every 4-6 hours as needed, with acetaminophen component not to exceed 75 mg/kg/day. Not approved for children <12 years.
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 dose (one tablet every 6 hours) and titrate cautiously. Monitor for respiratory depression, sedation, and constipation. Avoid doses >4 tablets per day unless tolerated.
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; life-threatening respiratory depression; accidental ingestion of even one dose of oxycodone, especially by children, can cause fatal overdose; neonatal opioid withdrawal syndrome; cytochrome P450 3A4 interaction with concurrent use of benzodiazepines or other CNS depressants; hepatotoxicity due to acetaminophen (dose-related).
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 opioid addiction, abuse, and misuse; life-threatening respiratory depression; risk of accidental ingestion; neonatal opioid withdrawal syndrome if used during pregnancy; risk of severe hypotension; risk of hepatotoxicity due to acetaminophen; risk of serotonin syndrome if co-administered with serotonergic drugs; adrenal insufficiency; risk of seizures; risk of increased intracranial pressure; severe renal or hepatic impairment; drug interactions with CNS depressants and CYP3A4 inhibitors/inducers.
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 of the formulation; 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 (for acetaminophen component).
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. High-fat meals may delay absorption of oxycodone, but does not affect total exposure.
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.
Pregnancy Category C (oxycodone) and D (acetaminophen at high doses). Oxycodone: Risk of neonatal opioid withdrawal syndrome (NOWS) with prolonged use in third trimester; risk of respiratory depression near term. Acetaminophen: Epidemiologic data not conclusively linked to major malformations at therapeutic doses, but high doses may be associated with fetal hepatotoxicity. FDA warns against chronic use during pregnancy due to NOWS.
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 with relative infant dose (RID) of 1.7-6.2% of maternal weight-adjusted dose; M/P ratio not well established (estimated ~1.3-3.7). Acetaminophen RID ~1-2%, M/P ratio ~0.91-1.0. Caution: Monitor infant for somnolence, respiratory depression, poor feeding. Avoid in breastfeeding women with CYP2D6 ultra-rapid metabolizer status due to increased morphine production.
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: Increased clearance and volume of distribution in pregnancy may require higher doses for adequate analgesia; dose should be titrated to effect. Acetaminophen: Pharmacokinetic changes minimal at therapeutic doses; no routine dose adjustment needed, but limit to <3000 mg/day to avoid maternal hepatotoxicity. Postpartum: Oxycodone doses may need reduction due to normalization of clearance.
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.
ROXICET 5/500 contains oxycodone (5 mg) and acetaminophen (500 mg). The acetaminophen component limits total daily use to avoid hepatotoxicity; maximum 4 g/day from all sources. Oxycodone is a Schedule II controlled substance with high abuse potential. Use with caution in patients with respiratory compromise, head injury, or hepatic impairment. Coadministration with alcohol or other CNS depressants increases sedation and respiratory depression risk. Consider naloxone co-prescription for high-risk patients.
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 only as prescribed; do not exceed 8 tablets in 24 hours due to acetaminophen.,Avoid alcohol and medications containing acetaminophen (e.g., Tylenol, cold remedies) to prevent liver damage.,Do not crush or chew tablets—swallow whole.,May cause drowsiness or dizziness; avoid driving or operating machinery until effects known.,Store securely out of reach of others; dispose of unused tablets via drug take-back program.,Do not share with others; misuse can cause addiction, overdose, or death.,Seek emergency help if signs of overdose: slow breathing, extreme drowsiness, confusion, or loss of consciousness.
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 ROXICET 5/500 vs CO-GESIC, answered by our medical review team.
ROXICET 5/500 is a Opioid Analgesic Combination that works by Oxycodone is a full opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and producing 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 ROXICET 5/500 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 ROXICET 5/500 is: 1-2 tablets (5-10 mg oxycodone / 325-650 mg acetaminophen) orally every 4-6 hours as needed for pain; maximum 12 tablets per day (60 mg oxycodone / 6000 mg acetaminophen) in 24 hours.. 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 ROXICET 5/500 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. ROXICET 5/500 is classified as Category C. Pregnancy Category C (oxycodone) and D (acetaminophen at high doses). Oxycodone: Risk of neonatal opioid withdrawal syndrome (NOWS) with prolonged use in third trimester; risk of r. 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.