Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
A/T/S vs COMBUNOX
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.
COMBUNOX is a fixed-dose combination of oxycodone, a full mu-opioid receptor agonist, and ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), thereby reducing prostaglandin synthesis.
Treatment of acne vulgaris (FDA-approved indication),Treatment of bacterial infections caused by susceptible organisms (off-label use for acne is the primary use)
FDA-approved: Short-term (up to 7 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.,Off-label: None commonly recognized.
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 tablet (ibuprofen 400 mg/oxycodone HCl 10 mg) orally every 4 to 6 hours as needed for pain; maximum 4 tablets per day.
Terminal elimination half-life: 1–2 hours (prolonged in hepatic impairment).
Oxycodone terminal half-life is 3.5-5.5 hours (mean ~3.8 hours) in immediate-release form; controlled-release formulations have a prolonged absorption phase with an effective half-life of 4.5-8 hours. Ibuprofen terminal half-life is 1.8-2.5 hours (mean ~2 hours). Clinical context: Oxycodone's half-life supports dosing every 4-6 hours (IR) or 12 hours (CR); ibuprofen's short half-life requires frequent dosing for sustained anti-inflammatory effect. In elderly or hepatic impairment, oxycodone half-life may increase to 6-8 hours; ibuprofen half-life may be slightly prolonged.
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.
Oxycodone: Primarily hepatic via CYP3A4 and CYP2D6 to active and inactive metabolites. Ibuprofen: Hepatic via CYP2C9 to inactive metabolites; also undergoes glucuronidation.
Renal: 10-20% (active drug and metabolites); Fecal: minimal; Biliary: not significant.
Oxycodone is primarily metabolized in the liver; metabolites are excreted mainly in urine. Approximately 87% of an oral dose is eliminated within 24 hours: 60-70% as oxycodone metabolites (mostly noroxycodone and oxymorphone conjugates) and 10-15% as unchanged oxycodone. Ibuprofen is rapidly metabolized and excreted; about 90% of a dose is eliminated in urine as metabolites (primarily hydroxylated and carboxylated forms) and <1% as unchanged drug. Biliary/fecal elimination accounts for <10% of each component.
70-90% bound to serum albumin.
Oxycodone: ~45% bound primarily to albumin. Ibuprofen: >99% bound to albumin. No displacement interactions likely at therapeutic concentrations.
0.5–0.8 L/kg (low Vd, minimal tissue penetration).
Oxycodone: Vd of 2.0-3.0 L/kg (mean ~2.6 L/kg), indicating extensive tissue distribution. Ibuprofen: Vd of 0.1-0.2 L/kg (mean ~0.15 L/kg), confined to plasma and extracellular fluid. Combined formulation Vd not significantly altered.
Topical: 1–5% (minimal systemic absorption).
Oral bioavailability of oxycodone: 60-87% (mean ~75%) with first-pass metabolism accounting for ~25% loss. Ibuprofen: >80% (mean ~95%) with minimal first-pass effect. Food reduces rate but not extent of absorption; taking with food may delay peak concentrations by 1-2 hours.
No specific adjustment required; drug is not renally eliminated.
GFR 30-89 m L/min: No adjustment needed. GFR <30 m L/min: Avoid use due to ibuprofen component. Hemodialysis: Not recommended.
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 oxycodone dose by 50% (e.g., consider alternative). Child-Pugh C: Avoid use (contraindicated).
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.
Not approved for pediatric use; safety and efficacy not established in patients <18 years.
No specific adjustment; use standard dosing with monitoring of antithrombin activity and bleeding risk.
Initiate at lower dose (e.g., 1 tablet of ibuprofen 200 mg/oxycodone HCl 5 mg) every 6 hours as needed; monitor for CNS depression and renal function. Maximum 4 tablets per day.
None.
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; risk of serious cardiovascular and gastrointestinal events with NSAIDs.
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.
Respiratory depression; addiction potential; CNS depression; hepatotoxicity; renal toxicity; gastrointestinal bleeding; cardiovascular thrombotic events; anaphylactic reactions; drug interactions with CYP3A4 inhibitors/inducers; avoid in severe hepatic impairment.
Hypersensitivity to erythromycin or any macrolide antibiotic.,Use with caution in patients with pre-existing QT prolongation or electrolyte abnormalities (relative contraindication).
Significant respiratory depression; acute or severe bronchial asthma; paralytic ileus; known hypersensitivity to oxycodone, ibuprofen, or any component; patients with gastrointestinal bleeding or perforation; advanced renal disease; coronary artery bypass graft (CABG) surgery perioperative pain; use of MAO inhibitors within 14 days.
No specific food interactions. Avoid excessive alcohol consumption as it may increase skin dryness.
Avoid alcohol. Taking with food decreases GI irritation. Grapefruit juice may increase oxycodone levels; limit intake. High-fat meals can delay but not reduce oxycodone absorption.
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.
COMBUNOX (oxycodone/ibuprofen) is pregnancy category C prior to 30 weeks and category D after 30 weeks. First trimester: limited data, potential neural tube defects with NSAIDs; second trimester: NSAID use associated with fetal renal dysfunction and oligohydramnios; third trimester: NSAIDs may cause premature closure of ductus arteriosus, pulmonary hypertension, and oligohydramnios; oxycodone may lead to neonatal opioid withdrawal syndrome (NOWS) with chronic use.
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.
Oxycodone excreted in breast milk; M/P ratio approximately 3.6:1. Ibuprofen minimal transfer (M/P ~0.01). Relative infant dose (RID) for oxycodone ~3.5% of maternal weight-adjusted dose; ibuprofen <0.1%. Potential for infant sedation, respiratory depression, and withdrawal. Use caution; avoid if mother is a CYP2D6 ultra-rapid metabolizer. American Academy of Pediatrics recommends use with monitoring.
No dose adjustment required. Systemic absorption from topical application is minimal and not significantly altered by pregnancy-related pharmacokinetic changes.
No specific dose adjustment for pregnancy is established. However, increased renal clearance in pregnancy may reduce ibuprofen levels; clinical significance unknown. Oxycodone pharmacokinetics altered: increased volume of distribution and clearance may require higher doses for analgesia. Use lowest effective dose and shortest duration. Avoid prolonged use >48 hours near term due to risk of premature ductus closure.
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.
Combunox contains ibuprofen 400 mg and oxycodone 5 mg. The fixed-dose combination limits flexibility; use only when both components are needed. Monitor for GI bleeding, renal impairment, and opioid-related respiratory depression. Avoid in patients with severe asthma, NSAID allergy, or opioid intolerance. Watch for drug interactions with anticoagulants, SSRIs, and CYP3A4 inhibitors/inducers. The combination increases risk of serotonin syndrome if used with other serotonergic drugs.
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 with food or milk to reduce stomach upset.,Do not exceed prescribed dose; can cause liver damage, stomach bleeding, or addiction.,Avoid alcohol while taking this medication.,May cause dizziness or drowsiness; do not drive until you know how it affects you.,Report sudden stomach pain, black stool, or vomiting blood.,Stop use and seek emergency care if signs of allergic reaction (rash, difficulty breathing) occur.,Do not combine with other NSAIDs or acetaminophen without consulting provider.,Store securely to prevent accidental overdose or misuse.
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 A/T/S vs COMBUNOX, 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.. COMBUNOX is a Analgesic Combination (Opioid + NSAID) that works by COMBUNOX is a fixed-dose combination of oxycodone, a full mu-opioid receptor agonist, and ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), thereby reducing prostaglandin synthesis.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between A/T/S and COMBUNOX 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 COMBUNOX is: 1 tablet (ibuprofen 400 mg/oxycodone HCl 10 mg) orally every 4 to 6 hours as needed for pain; maximum 4 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 COMBUNOX 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 . COMBUNOX is classified as Category C. COMBUNOX (oxycodone/ibuprofen) is pregnancy category C prior to 30 weeks and category D after 30 weeks. First trimester: limited data, potential neural tube defects with NSAIDs; se. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.