Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
CO-GESIC vs CODAMINE
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.
Codeine is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. It is a prodrug converted to morphine via CYP2D6.
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.
Mild to moderate pain,Cough suppression (off-label)
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.
Adults: 1-2 tablets (codeine 30 mg + acetaminophen 500 mg per tablet) orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Terminal elimination half-life is approximately 2–4 hours in adults with normal renal function; prolonged in renal impairment.
Terminal elimination half-life: 4–6 hours in adults; prolonged to 8–12 hours in renal impairment (Cr Cl <30 m L/min)
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).
Hepatic via CYP2D6 to morphine (active) and CYP3A4 to norcodeine; also glucuronidation.
Primarily renal (60–70% as unchanged drug and metabolites); minor biliary/fecal excretion (<5%).
Renal: 60% unchanged; Biliary/Fecal: 30% as metabolites; 10% other
<20%; primarily binds to albumin.
~92% bound primarily to albumin and alpha-1-acid glycoprotein
1.2–1.9 L/kg; suggests extensive distribution into total body water.
Vd: 1.2 L/kg (range 0.8–1.6 L/kg), indicating extensive tissue distribution
Oral: 85–95%; rectal: 70–80%.
Oral: 65–75% (first-pass effect); Rectal: 50–60%; Intramuscular: 90%
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.
GFR 30-50 m L/min: Use with caution, reduce dose by 25-50% or extend interval to every 6-8 hours. GFR <30 m L/min: Avoid use due to risk of codeine accumulation and toxicity.
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. Child-Pugh Class B: Reduce dose by 50% and monitor for sedation. Child-Pugh Class C: Contraindicated.
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.
Weight-based codeine dosing: 0.5-1 mg/kg every 4-6 hours as needed; maximum 60 mg per dose. Acetaminophen component: 10-15 mg/kg every 4-6 hours; maximum 75 mg/kg per day. Not recommended in children under 12 years due to risk of 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.
Start at lower end of dosing range (e.g., 1 tablet every 6 hours) due to increased sensitivity and risk of respiratory depression, constipation, and sedation. Monitor renal and hepatic function.
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.
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; AND RISK OF MEDICATION ERRORS.
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 respiratory depression, especially in children; ultra-rapid metabolizers (CYP2D6 duplications) may experience life-threatening toxicity; avoid use post-tonsillectomy/adenoidectomy in children; risk of opioid-induced hyperalgesia; adrenal insufficiency; severe hypotension; seizures; serotonin syndrome with serotonergic drugs; GI obstruction; impaired mental/physical abilities.
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; GI obstruction; known hypersensitivity; use in children <12 years; use in children <18 years post-tonsillectomy/adenoidectomy; pregnant women during labor (prolonged use); concomitant MAOIs or within 14 days.
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 grapefruit juice as it may alter metabolism of codeine. High-fiber meals may help with constipation; avoid excessive alcohol. St. John's Wort may reduce codeine efficacy.
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.
CODAMINE is classified as FDA Pregnancy Category D. First trimester: Associated with increased risk of cardiovascular and neural tube defects. Second trimester: Potential for fetal growth restriction and oligohydramnios. Third trimester: Risk of neonatal withdrawal, respiratory depression, and persistent pulmonary hypertension.
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.
CODAMINE is excreted into breast milk with a milk-to-plasma (M/P) ratio of approximately 1.5. Breastfeeding is not recommended due to potential for infant sedation, respiratory depression, and withdrawal. If unavoidable, monitor infant for lethargy and poor feeding.
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 during pregnancy may require 20-30% dose increase to maintain therapeutic levels. Due to risk of maternal hypotension and placental hypoperfusion, use lowest effective dose with close monitoring. Consider therapeutic drug monitoring if available.
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.
Codamine is a combination of codeine and an antihistamine (e.g., promethazine or chlorpheniramine). Caution: risk of respiratory depression, especially in elderly or with lung disease. Monitor for constipation. Avoid in children under 12 due to risk of respiratory depression. Use lowest effective dose for shortest duration. Antihistamine component may cause anticholinergic effects (dry mouth, urinary retention, blurred vision).
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 recommended dose; risk of serious side effects like slowed breathing.,Avoid alcohol and other sedatives (benzodiazepines, sleeping pills) as they increase drowsiness and breathing problems.,Do not drive or operate machinery until you know how this medication affects you.,Take with food to reduce stomach upset; drink plenty of fluids to prevent constipation.,Stop use and seek medical help if you experience difficulty breathing, severe dizziness, or allergic reaction.,Store safely out of reach of children; dispose of unused medication properly to prevent accidental overdose.,Do not use if you have a history of drug abuse or addiction.,Inform your doctor if you are pregnant, breastfeeding, or have lung/liver/kidney/thyroid problems.
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 CODAMINE, 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.. CODAMINE is a Opioid Analgesic Combination that works by Codeine is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. It is a prodrug converted to morphine via CYP2D6.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between CO-GESIC and CODAMINE 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 CODAMINE is: Adults: 1-2 tablets (codeine 30 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 CO-GESIC and CODAMINE 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. CODAMINE is classified as Category C. CODAMINE is classified as FDA Pregnancy Category D. First trimester: Associated with increased risk of cardiovascular and neural tube defects. Second trimester: Potential for fetal. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.