Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
LORTAB 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
Hydrocodone is a mu-opioid receptor agonist; acetaminophen inhibits cyclooxygenase (COX) and modulates pain pathways centrally.
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.
Moderate to severe pain management (FDA),Off-label: acute pain, 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.
1-2 tablets (each containing 5 mg hydrocodone/325 mg acetaminophen) orally every 4-6 hours as needed for pain. Maximum acetaminophen 3000 mg/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.
Hydrocodone: 3.3-4.4 hours in adults; prolonged in hepatic/renal impairment (up to 6-8 hours). Clinical context: requires 4-6 hour dosing intervals; steady-state in ~24 hours.
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Hydrocodone: CYP3A4, CYP2D6; acetaminophen: hepatic conjugation (glucuronidation, sulfation) and CYP450 (minor).
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).
Renal: ~90% (unchanged: ~5% hydrocodone, ~60% hydromorphone and other conjugates; codeine-like metabolites). Biliary/fecal: minor (<10%).
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Hydrocodone: ~20-30% bound (primarily albumin).
<20%; primarily binds to albumin.
Hydrocodone: 3.3-4.7 L/kg; indicates extensive tissue distribution.
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Oral: ~90% (first-pass metabolism reduces to ~50% due to extensive hepatic extraction; absolute bioavailability not well defined, but high oral absorption).
Oral: 85–95%; rectal: 70–80%.
Hydrocodone: e GFR 30-59 m L/min: administer 50-75% of usual dose; e GFR 15-29 m L/min: 50% of usual dose; e GFR <15 m L/min: avoid or use with caution. Acetaminophen: no specific GFR-based adjustment; avoid in severe renal impairment due to metabolite 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.
Hydrocodone: Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% and monitor; Class C: avoid. Acetaminophen: reduce dose or avoid in significant liver disease; maximum 2000 mg/day in mild-moderate impairment.
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 <18 years due to risk of respiratory depression and acetaminophen toxicity. In specific circumstances, weight-based dosing for hydrocodone 0.1-0.2 mg/kg/dose every 4-6 hours, max 10 mg/dose; acetaminophen 10-15 mg/kg/dose, max 60 mg/kg/day, not to exceed 3000 mg/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 at the low end of dosing range (e.g., 1 tablet of 5 mg hydrocodone/325 mg acetaminophen every 6 hours). Monitor for respiratory depression, sedation, and constipation. Avoid acetaminophen >3000 mg/day due to hepatotoxicity 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; neonatal opioid withdrawal syndrome; risk with CYP3A4 inhibitors or discontinuation; risk of medication errors.
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, misuse; respiratory depression; head injury; GI obstruction; hepatic toxicity; renal impairment; hypotension; adrenal insufficiency; seizures; serotonin syndrome; severe hypotension; risk with MAOIs; pregnancy; lactation.
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; respiratory depression; acute/severe asthma; GI obstruction; suspected surgical abdomen; severe hepatic impairment; concurrent use with MAOIs or within 14 days.
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 grapefruit and grapefruit juice as they may alter hydrocodone metabolism. Alcohol must be strictly avoided due to additive CNS depression and increased acetaminophen hepatotoxicity. 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.
FDA Category C in 1st and 2nd trimesters; increased risk of neural tube defects and congenital heart defects with codeine use; risk of respiratory depression and neonatal withdrawal syndrome in 3rd trimester with prolonged use.
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.
Codeine is excreted into breast milk; M/P ratio approximately 2.5 for morphine (active metabolite); potential for infant CNS depression; use caution, especially in CYP2D6 ultra-rapid metabolizers.
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.
Increased clearance of codeine in pregnancy may require higher doses or more frequent intervals; avoid in 3rd trimester due to risk of neonatal respiratory depression; use lowest effective dose for shortest duration.
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.
Lortab (hydrocodone/acetaminophen) carries a boxed warning for respiratory depression, misuse/abuse, and neonatal opioid withdrawal syndrome. The acetaminophen component imposes a maximum dose of 4000 mg/day; caution with hepatic impairment. Use the lowest effective dose for the shortest duration. Consider naloxone co-prescribing 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 exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Do not crush, chew, or dissolve tablets; swallow whole.,Avoid alcohol; it increases risk of liver damage and respiratory depression.,Do not drive or operate machinery until you know how Lortab affects you.,Discontinue and seek medical help if you experience signs of allergic reaction (rash, difficulty breathing) or liver injury (yellowing skin/eyes, dark urine).,Store securely out of reach of others; dispose of unused medication via take-back programs.
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 LORTAB vs CO-GESIC, answered by our medical review team.
LORTAB is a Opioid analgesic combination that works by Hydrocodone is a mu-opioid receptor agonist; acetaminophen inhibits cyclooxygenase (COX) and modulates pain pathways centrally.. 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 LORTAB and CO-GESIC depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of LORTAB is: 1-2 tablets (each containing 5 mg hydrocodone/325 mg acetaminophen) orally every 4-6 hours as needed for pain. Maximum acetaminophen 3000 mg/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 LORTAB 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. LORTAB is classified as Category C. FDA Category C in 1st and 2nd trimesters; increased risk of neural tube defects and congenital heart defects with codeine use; risk of respiratory depression and neonatal withdrawa. 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.