Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
CO-GESIC vs ANEXSIA 7.5/325
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Hydrocodone is a mu-opioid receptor agonist, producing analgesia and euphoria. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.
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.
Management of moderate to moderately severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate
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.
1 tablet (hydrocodone 7.5 mg / acetaminophen 325 mg) orally every 4 to 6 hours as needed for pain; maximum 6 tablets per day (hydrocodone 45 mg / acetaminophen 1950 mg).
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Hydrocodone: 3.8-4.5 hours (immediate-release). Acetaminophen: 2-3 hours. Clinical note: Half-life prolonged in hepatic impairment; requires dose adjustment.
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).
Hydrocodone: CYP3A4 and CYP2D6; Acetaminophen: primarily via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1.
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Renal: ~90-100% as hydrocodone metabolites (conjugated) and unchanged hydrocodone; ~60% as acetaminophen metabolites (glucuronide, sulfate, cysteine); <5% unchanged acetaminophen. Biliary/fecal: <5%.
<20%; primarily binds to albumin.
Hydrocodone: ~20-30% (albumin). Acetaminophen: ~10-25% (albumin).
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Hydrocodone: 3-4 L/kg (extensive tissue distribution). Acetaminophen: ~1 L/kg (uniformly distributed).
Oral: 85–95%; rectal: 70–80%.
Oral: Hydrocodone ~70% (high first-pass metabolism); Acetaminophen ~85-90% (minimal first-pass).
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.
For GFR 30-59 m L/min: administer every 6 hours; maximum 4 tablets per day. For GFR 15-29 m L/min: administer every 8 hours; maximum 3 tablets per day. For GFR <15 m L/min: not recommended due to accumulation of metabolites.
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.
Child-Pugh Class A: no adjustment necessary. Child-Pugh Class B: reduce dose by 25-50% and extend dosing interval to every 6-8 hours; maximum 4 tablets per day. Child-Pugh Class C: contraindicated due to risk of hepatotoxicity.
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.
Not recommended for pediatric patients; safety and efficacy not established for children under 18 years. For adolescents ≥18 years: adult dosing.
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.
Initiate at 1 tablet (hydrocodone 5 mg / acetaminophen 325 mg) every 6 hours as needed; titrate cautiously due to increased sensitivity, decreased renal function, and risk of respiratory depression. Maximum 4 tablets per day.
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; hepatotoxicity due to 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.
Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use of alcohol, benzodiazepines, or other CNS depressants; hepatotoxicity; severe hypotension; adrenal insufficiency; seizures; GI obstruction; impaired mental/physical abilities; use in elderly, cachectic, or debilitated patients; renal impairment; hepatic impairment; pregnancy; labor and delivery; nursing mothers; pediatric use; driving and operating machinery.
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).
Significant respiratory depression; acute or severe bronchial asthma; known or suspected GI obstruction; hypersensitivity to hydrocodone or acetaminophen; concomitant use of MAOIs or within 14 days of such therapy.
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.
Avoid alcohol consumption due to increased risk of acetaminophen hepatotoxicity and CNS depression. No specific food restrictions, but grapefruit juice may theoretically affect hydrocodone metabolism via CYP3A4 inhibition; however, clinical significance is uncertain.
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.
FDA Category C (hydrocodone) and Category D (acetaminophen) in third trimester. First trimester: Acetaminophen associated with rare gastroschisis; hydrocodone risk of neural tube defects. Second trimester: No major malformations except with prolonged opioid use. Third trimester: Acetaminophen safe; hydrocodone risk of neonatal opioid withdrawal syndrome (NOWS). Avoid near term.
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.
Hydrocodone/acetaminophen excreted in breast milk. M/P ratio unknown. Hydrocodone relative infant dose <3% of weight-adjusted maternal dose. Acetaminophen relative infant dose <2%. Use with caution; monitor infant for sedation, apnea, poor feeding. Highest risk in CYP2D6 ultrarapid metabolizers.
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.
Increased clearance of hydrocodone in pregnancy may require dose adjustment; monitor for inadequate analgesia. Acetaminophen pharmacokinetics unchanged. Avoid high doses (hepatotoxicity risk). Consider baseline hepatic function. No specific dose adjustment recommended; titrate to effect.
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.
ANEXSIA 7.5/325 (hydrocodone/acetaminophen) carries a boxed warning for acetaminophen hepatotoxicity; maximum acetaminophen dose from all sources should not exceed 4 g/day. Hydrocodone is metabolized by CYP2D6 to hydromorphone; ultrarapid metabolizers may experience toxicity. Avoid concurrent use with other CNS depressants including alcohol. Prescribe with caution in patients with renal impairment (hydrocodone accumulation) or hepatic impairment (acetaminophen toxicity). Monitor for signs of respiratory depression, especially at therapy initiation and dose titration. Use the lowest effective dose for the shortest duration.
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.
Do not exceed 6 tablets per day due to acetaminophen content.,Avoid alcohol while taking this medication.,Do not drive or operate heavy machinery until you know how this medication affects you.,Take exactly as prescribed; do not share with others.,Seek emergency help if you experience difficulty breathing, severe drowsiness, or signs of allergic reaction.,Store securely out of reach of children and dispose of unused medication properly.
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 CO-GESIC vs ANEXSIA 7.5/325, answered by our medical review team.
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.. ANEXSIA 7.5/325 is a Opioid Analgesic Combination that works by Hydrocodone is a mu-opioid receptor agonist, producing analgesia and euphoria. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between CO-GESIC and ANEXSIA 7.5/325 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 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.. The standard adult dose of ANEXSIA 7.5/325 is: 1 tablet (hydrocodone 7.5 mg / acetaminophen 325 mg) orally every 4 to 6 hours as needed for pain; maximum 6 tablets per day (hydrocodone 45 mg / acetaminophen 1950 mg).. 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 CO-GESIC and ANEXSIA 7.5/325 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. 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. ANEXSIA 7.5/325 is classified as Category C. FDA Category C (hydrocodone) and Category D (acetaminophen) in third trimester. First trimester: Acetaminophen associated with rare gastroschisis; hydrocodone risk of neural tube d. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.