Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ANEXSIA 7.5/325 vs CODAMINE
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, producing analgesia and euphoria. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.
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.
Management of moderate to moderately severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate
Mild to moderate pain,Cough suppression (off-label)
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).
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.
Hydrocodone: 3.8-4.5 hours (immediate-release). Acetaminophen: 2-3 hours. Clinical note: Half-life prolonged in hepatic impairment; requires dose adjustment.
Terminal elimination half-life: 4–6 hours in adults; prolonged to 8–12 hours in renal impairment (Cr Cl <30 m L/min)
Hydrocodone: CYP3A4 and CYP2D6; Acetaminophen: primarily via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1.
Hepatic via CYP2D6 to morphine (active) and CYP3A4 to norcodeine; also glucuronidation.
Renal: ~90-100% as hydrocodone metabolites (conjugated) and unchanged hydrocodone; ~60% as acetaminophen metabolites (glucuronide, sulfate, cysteine); <5% unchanged acetaminophen. Biliary/fecal: <5%.
Renal: 60% unchanged; Biliary/Fecal: 30% as metabolites; 10% other
Hydrocodone: ~20-30% (albumin). Acetaminophen: ~10-25% (albumin).
~92% bound primarily to albumin and alpha-1-acid glycoprotein
Hydrocodone: 3-4 L/kg (extensive tissue distribution). Acetaminophen: ~1 L/kg (uniformly distributed).
Vd: 1.2 L/kg (range 0.8–1.6 L/kg), indicating extensive tissue distribution
Oral: Hydrocodone ~70% (high first-pass metabolism); Acetaminophen ~85-90% (minimal first-pass).
Oral: 65–75% (first-pass effect); Rectal: 50–60%; Intramuscular: 90%
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.
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 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.
Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% and monitor for sedation. Child-Pugh Class C: Contraindicated.
Not recommended for pediatric patients; safety and efficacy not established for children under 18 years. For adolescents ≥18 years: adult dosing.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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 ANEXSIA 7.5/325 vs CODAMINE, answered by our medical review team.
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.. 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 ANEXSIA 7.5/325 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 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).. 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 ANEXSIA 7.5/325 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. 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. 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.