Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
LORTAB vs ANEXSIA 5/325
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.
Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.
Moderate to severe pain management (FDA),Off-label: acute pain, chronic pain
Management of moderate to moderately severe pain where an opioid analgesic is appropriate
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 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.
Oxycodone: terminal half-life 3.2-4.3 hours (immediate-release); prolonged in hepatic impairment. Acetaminophen: terminal half-life 2-3 hours (therapeutic doses); prolonged in hepatic impairment or overdose.
Hydrocodone: CYP3A4, CYP2D6; acetaminophen: hepatic conjugation (glucuronidation, sulfation) and CYP450 (minor).
Hydrocodone: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (hydromorphone). Acetaminophen: hepatic metabolism via conjugation (glucuronidation, sulfation) and CYP2E1-mediated oxidation to toxic NAPQI.
Renal: ~90% (unchanged: ~5% hydrocodone, ~60% hydromorphone and other conjugates; codeine-like metabolites). Biliary/fecal: minor (<10%).
Oxycodone: renal excretion of metabolites (conjugated and unconjugated) and parent drug; ~10% excreted unchanged. Acetaminophen: renal excretion of metabolites (glucuronide and sulfate conjugates); ~2-4% excreted unchanged.
Hydrocodone: ~20-30% bound (primarily albumin).
Oxycodone: 38-45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10-25% bound to albumin at therapeutic concentrations.
Hydrocodone: 3.3-4.7 L/kg; indicates extensive tissue distribution.
Oxycodone: Vd 2.0-3.0 L/kg; distributes extensively into tissues. Acetaminophen: Vd 0.8-1.0 L/kg; relatively uniform distribution.
Oral: ~90% (first-pass metabolism reduces to ~50% due to extensive hepatic extraction; absolute bioavailability not well defined, but high oral absorption).
Oxycodone: oral bioavailability 60-87% (immediate-release). Acetaminophen: oral bioavailability 88-98% (therapeutic doses).
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 30-50 m L/min: use with caution, increase dosing interval to every 6 hours; GFR <30 m L/min: avoid use due to hydrocodeone accumulation.
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 A: no adjustment; Child-Pugh B: reduce dose by 50% and monitor; Child-Pugh C: contraindicated.
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.
Not recommended for children under 18 years due to risk of respiratory depression.
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 with lowest dose (1 tablet every 6 hours), monitor renal and hepatic function, and avoid in frail elderly due to increased fall and cognitive impairment risk.
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; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and hepatotoxicity from acetaminophen overdose.
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.
Risk of opioid 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; adrenal insufficiency; severe hypotension; gastrointestinal obstruction; seizure; and serotonin syndrome.
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 or acetaminophen; significant respiratory depression; acute or severe bronchial asthma; GI obstruction; known or suspected paralytic ileus; severe hepatic impairment; and concurrent use of MAOIs 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 alcohol. Grapefruit juice may enhance side effects; limit intake. Take with food to reduce gastrointestinal discomfort.
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: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal renal toxicity, oligohydramnios, and premature closure of ductus arteriosus. Use only if clearly needed.
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.
Paracetamol and hydrocodone are excreted in breast milk. M/P ratio: paracetamol ~1.0, hydrocodone ~1.0-2.0. Use with caution; monitor infant for drowsiness and respiratory depression. Consider risk of infant sedation with long-term use.
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.
Increased clearance in pregnancy may require dose adjustment. Monitor for pain control and adverse effects; no fixed dose change recommended. Consider lower starting dose due to potential fetal risks. Avoid chronic use; taper if possible.
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.
ANEXSIA 5/325 contains hydrocodone 5 mg and acetaminophen 325 mg. Maximum acetaminophen dose from all sources should not exceed 4 g/day in adults; avoid in severe hepatic impairment. Hydrocodone is a Schedule II controlled substance with abuse potential; monitor for respiratory depression, especially in opioid-naive patients. Use with caution in patients with COPD, sleep apnea, or increased intracranial pressure. Consider naloxone co-prescription for high-risk patients. For acute pain, limit duration to 3-7 days.
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.,Do not consume alcohol or other sedatives (e.g., benzodiazepines) while taking this medication.,Avoid other products containing acetaminophen (e.g., Tylenol, cold remedies) to prevent liver damage.,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 others; dispose of unused medication via drug take-back programs.,Seek emergency help if you have trouble breathing, severe drowsiness, or signs of allergic reaction.
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 ANEXSIA 5/325, 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.. ANEXSIA 5/325 is a Opioid Analgesic Combination that works by Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic effects, primarily through central COX-2 inhibition and activation of descending serotonergic pathways.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between LORTAB and ANEXSIA 5/325 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 ANEXSIA 5/325 is: 1-2 tablets 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 ANEXSIA 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. 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. ANEXSIA 5/325 is classified as Category C. First trimester: Associated with increased risk of neural tube defects and cardiovascular malformations; avoid use. Second and third trimesters: Chronic exposure may cause fetal re. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.