Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
A/T/S vs ACETAMINOPHEN AND HYDROCODONE BITARTRATE
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
A/T/S (erythromycin) is a macrolide antibiotic that acts by binding to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis and bacterial growth.
Acetaminophen: analgesic and antipyretic effects via inhibition of cyclooxygenase (COX) and activation of descending serotonergic pathways; central action. Hydrocodone: mu-opioid receptor agonist; activates G-protein coupled receptors to modulate pain perception and emotional response.
Treatment of acne vulgaris (FDA-approved indication),Treatment of bacterial infections caused by susceptible organisms (off-label use for acne is the primary use)
Moderate to moderately severe pain,Cough suppression (hydrocodone; off-label)
Dosing is individualized based on antithrombin activity level. For acute thrombotic events: initial bolus of 30-50 IU/kg followed by maintenance dosing to achieve target activity levels (80-120% of normal). Prophylaxis: 40-60 IU/kg every 24 hours.
1-2 tablets (containing 5-10 mg hydrocodone and 300-325 mg acetaminophen) orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
Terminal elimination half-life: 1–2 hours (prolonged in hepatic impairment).
Acetaminophen: 2-3 hours in adults; prolonged in hepatic impairment (up to 5 hours). Hydrocodone: 3.8-4.5 hours (range 3-5 hours) in healthy adults; prolonged in elderly or hepatic/renal impairment. Clinical context: repeated dosing may require extended intervals in renal impairment.
Antithrombin is a glycoprotein; its metabolism involves cellular uptake and catabolism, but specific CYP450 enzymes are not involved. Degradation occurs via proteolysis and reticuloendothelial system clearance.
Acetaminophen: primarily via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation; minor CYP2E1 oxidation to NAPQI (toxic metabolite). Hydrocodone: CYP3A4 and CYP2D6; N-demethylation to norhydrocodone; O-demethylation to hydromorphone (CYP2D6).
Renal: 10-20% (active drug and metabolites); Fecal: minimal; Biliary: not significant.
Acetaminophen: primarily renal excretion of conjugated metabolites (glucuronide and sulfate) with approximately 5% excreted unchanged. Hydrocodone: renal excretion as unchanged drug and metabolites (O-demethylated and N-demethylated); total renal excretion accounts for about 60-70% of dose (parent and metabolites). Biliary/fecal elimination is minimal.
70-90% bound to serum albumin.
Acetaminophen: 10-25% bound, nonspecific binding to albumin. Hydrocodone: 25-50% bound, primarily to albumin and alpha-1-acid glycoprotein.
0.5–0.8 L/kg (low Vd, minimal tissue penetration).
Acetaminophen: 0.8-1.0 L/kg, indicating distribution into total body water; clinically relevant for loading dose calculations. Hydrocodone: 3.0-4.0 L/kg, suggesting extensive tissue distribution; higher Vd may require higher loading doses but has no clinical target.
Topical: 1–5% (minimal systemic absorption).
Acetaminophen: oral bioavailability 85-95% (first-pass metabolism minimal). Hydrocodone: oral bioavailability about 25-45% due to first-pass hepatic metabolism; significant interindividual variability.
No specific adjustment required; drug is not renally eliminated.
GFR 10-50 m L/min: administer every 6 hours; GFR <10 m L/min: administer every 8 hours; avoid in severe impairment due to acetaminophen metabolite accumulation.
No specific adjustment; antithrombin is produced in the liver, but exogenous replacement does not require dose adjustment in hepatic impairment.
Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% or extend interval; Child-Pugh C: use with caution, avoid if possible, consider alternative therapy.
Dosing based on weight and antithrombin levels; typical initial dose 30-50 IU/kg, followed by maintenance to achieve target levels. Clinical trial data limited in neonates.
Dosing based on hydrocodone component: 0.1-0.2 mg/kg/dose every 4-6 hours; maximum daily acetaminophen limit: 75 mg/kg/day; not recommended for children <2 years.
No specific adjustment; use standard dosing with monitoring of antithrombin activity and bleeding risk.
Initiate at lowest effective dose, typically 1 tablet (2.5-5 mg hydrocodone) every 6 hours; monitor for respiratory depression and acetaminophen toxicity; avoid in frail elderly with hepatic impairment.
None.
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of acetaminophen; neonatal opioid withdrawal syndrome; interaction with alcohol; risk of medication errors.
Hypersensitivity reactions including anaphylaxis have occurred.,Prolonged use may result in overgrowth of nonsusceptible organisms including fungi.,Use with caution in patients with hepatic impairment.,Potential for QT prolongation and ventricular arrhythmias, especially with intravenous administration or concomitant drugs that prolong QT interval.
Hepatotoxicity from acetaminophen overdose; respiratory depression; increased intracranial pressure; CNS depression; elderly/debilitated patients; renal impairment; opioid-induced hyperalgesia; serotonin syndrome; interaction with CNS depressants; risk of adrenal insufficiency; severe hypotension; use in patients with gastrointestinal obstruction; convulsion risk; severe hepatic impairment; urinary retention; acute abdominal conditions; hypothyroidism; prostatic hypertrophy; adrenocortical insufficiency; pregnancy/lactation; pediatric use; geriatric use; renal impairment; hepatic impairment.
Hypersensitivity to erythromycin or any macrolide antibiotic.,Use with caution in patients with pre-existing QT prolongation or electrolyte abnormalities (relative contraindication).
Hypersensitivity to acetaminophen or hydrocodone; significant respiratory depression; acute or severe bronchial asthma; upper airway obstruction; known or suspected gastrointestinal obstruction; paralytic ileus; concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days; severe hepatic impairment (acetaminophen toxicity risk); acute alcoholism.
No specific food interactions. Avoid excessive alcohol consumption as it may increase skin dryness.
Avoid alcohol consumption during therapy; ethanol increases acetaminophen hepatotoxicity risk and enhances CNS depression. Grapefruit juice may inhibit CYP2D6 (minor effect) but no significant clinical interaction. No other specific food restrictions.
FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; no adequate human studies in first trimester. Topical erythromycin has minimal systemic absorption; risk to fetus is low across all trimesters.
First trimester: Acetaminophen considered low risk; hydrocodone is a pregnancy category C drug. Data from retrospective studies suggest a small increased risk of certain congenital malformations (e.g., neural tube defects, cleft palate) with first trimester opioid use, but absolute risk is low. Second trimester: Low risk as above. Third trimester: Prolonged use of hydrocodone can cause neonatal opioid withdrawal syndrome (NOWS); acetaminophen is safe. Use only if benefit outweighs risk.
Compatible with breastfeeding. Erythromycin is excreted into breast milk in small amounts (M/P ratio approximately 0.5). Topical use results in negligible systemic exposure; unlikely to cause adverse effects in nursing infants.
Acetaminophen excretion in breast milk is low (M/P ratio ~0.9). Hydrocodone is excreted in small amounts (M/P ratio ~2.1). The relative infant dose is estimated to be 2.5-3.5% of maternal weight-adjusted dose for hydrocodone. Monitor infant for sedation and respiratory depression. Consider benefit to mother and potential neonatal opioid withdrawal if used chronically.
No dose adjustment required. Systemic absorption from topical application is minimal and not significantly altered by pregnancy-related pharmacokinetic changes.
During pregnancy, increased plasma volume and enhanced hepatic clearance may reduce serum concentrations of both drugs. However, dosing adjustments are not routinely recommended due to risk of undertreatment. Use the lowest effective dose of hydrocodone for the shortest duration. For acetaminophen, maximum daily dose should not exceed 3000 mg to avoid hepatotoxicity.
A/T/S (erythromycin 2% topical solution) is indicated for acne vulgaris. Avoid contact with eyes, mouth, and mucous membranes. May cause skin dryness or irritation; use moisturizer. Effectiveness may decrease with prolonged use due to bacterial resistance. Not recommended for use with other topical erythromycin products or clindamycin to avoid antagonism.
Acetaminophen-hydrocodone is contraindicated in severe respiratory depression, acute or severe bronchial asthma, and known hypersensitivity. Monitor for respiratory depression, especially in elderly or debilitated patients. Avoid use with other acetaminophen-containing products to prevent hepatotoxicity. Hydrocodone is a prodrug metabolized by CYP2D6 to hydromorphone; CYP2D6 ultrarapid metabolizers may experience toxicity. Use with caution in patients with head injury, increased intracranial pressure, or severe hepatic impairment. Naloxone is the reversal agent for opioid effects; acetylcysteine for acetaminophen overdose.
Apply a thin layer to affected areas twice daily after washing.,Avoid contact with eyes, lips, and mouth; if contact occurs, rinse thoroughly with water.,May cause stinging, burning, or peeling; if irritation persists, consult your doctor.,Use sunscreen daily as this medication may increase sensitivity to sunlight.,Do not use more than prescribed; overuse may increase side effects without improving results.,Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding.,Keep away from open flames or heat sources; product is flammable.
Take exactly as prescribed; do not increase dose or frequency without consulting your doctor.,Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of severe drowsiness and respiratory depression.,Do not exceed 4000 mg of acetaminophen per day from all sources; check labels of other medications.,This medication may cause dizziness or drowsiness; avoid driving or operating heavy machinery until you know how it affects you.,Store securely out of reach of others, especially children, as misuse can cause overdose and death.,Do not stop abruptly; withdrawal may occur. Taper under medical supervision.,Contact emergency if you experience trouble breathing, extreme drowsiness, or signs of allergic reaction.,Report any history of substance abuse, as this medication has abuse potential.
No interactions on record
"Hydrocodone, an opioid agonist, and scopolamine, an anticholinergic agent, both exhibit central nervous system (CNS) depressant effects. When co-administered, their combined activity can lead to additive CNS depression, resulting in enhanced sedation, respiratory depression, and cognitive impairment. This interaction may also increase the risk of constipation and urinary retention due to additive anticholinergic effects from both drugs."
"Pargyline, a monoamine oxidase inhibitor (MAOI), irreversibly inhibits the metabolism of amines, leading to increased intraneuronal stores of norepinephrine. Hydrocodone, a semisynthetic opioid, can release these stored catecholamines, potentially causing a hypertensive crisis, serotonin syndrome, or CNS excitation. Coadministration may also result in excessive sedation and respiratory depression due to additive CNS depressant effects, requiring immediate clinical attention."
"Hydrocodone, an opioid agonist, and oxprenolol, a non-selective beta-adrenoceptor antagonist, are both central nervous system (CNS) depressants. Their combined use can lead to additive CNS depression, resulting in excessive sedation, respiratory depression, hypotension, and bradycardia. This interaction is particularly dangerous in patients with compromised cardiac or respiratory function, potentially leading to coma or death."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about A/T/S vs ACETAMINOPHEN AND HYDROCODONE BITARTRATE, answered by our medical review team.
A/T/S is a Macrolide antibiotic that works by A/T/S (erythromycin) is a macrolide antibiotic that acts by binding to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis and bacterial growth.. ACETAMINOPHEN AND HYDROCODONE BITARTRATE is a Opioid Agonist that works by Acetaminophen: analgesic and antipyretic effects via inhibition of cyclooxygenase (COX) and activation of descending serotonergic pathways; central action. Hydrocodone: mu-opioid receptor agonist; activates G-protein coupled receptors to modulate pain perception and emotional response.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between A/T/S and ACETAMINOPHEN AND HYDROCODONE BITARTRATE 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 A/T/S is: Dosing is individualized based on antithrombin activity level. For acute thrombotic events: initial bolus of 30-50 IU/kg followed by maintenance dosing to achieve target activity levels (80-120% of normal). Prophylaxis: 40-60 IU/kg every 24 hours.. The standard adult dose of ACETAMINOPHEN AND HYDROCODONE BITARTRATE is: 1-2 tablets (containing 5-10 mg hydrocodone and 300-325 mg acetaminophen) 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 A/T/S and ACETAMINOPHEN AND HYDROCODONE BITARTRATE 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. A/T/S is classified as Category C. FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; no adequate human studies in first trimester. Topical erythromycin has minimal systemic absorption; risk . ACETAMINOPHEN AND HYDROCODONE BITARTRATE is classified as Category D/X. First trimester: Acetaminophen considered low risk; hydrocodone is a pregnancy category C drug. Data from retrospective studies suggest a small increased risk of certain congenital. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.