Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
COMBUNOX vs IBU
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Non-selective inhibitor of cyclooxygenase (COX-1 and COX-2), decreasing prostaglandin synthesis, thereby reducing inflammation, pain, and fever.
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.
Rheumatoid arthritis,Osteoarthritis,Mild to moderate pain,Dysmenorrhea,Fever,Patent ductus arteriosus closure in neonates (off-label)
1 tablet (ibuprofen 400 mg/oxycodone HCl 10 mg) orally every 4 to 6 hours as needed for pain; maximum 4 tablets per day.
200-800 mg orally every 6-8 hours as needed; maximum 3200 mg/day. For OTC use: 200-400 mg every 4-6 hours; max 1200 mg/day.
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.
Terminal elimination half-life: 2-4 hours in adults; prolonged in neonates (30 hours) and elderly (up to 6 hours). No accumulation with recommended dosing due to short t½.
Oxycodone: Primarily hepatic via CYP3A4 and CYP2D6 to active and inactive metabolites. Ibuprofen: Hepatic via CYP2C9 to inactive metabolites; also undergoes glucuronidation.
Hepatic metabolism primarily via CYP2C9 to inactive metabolites; minor pathways include CYP2C8.
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.
Renal (90% as conjugated metabolites, 10% unchanged), biliary/fecal (minor, <5%)
Oxycodone: ~45% bound primarily to albumin. Ibuprofen: >99% bound to albumin. No displacement interactions likely at therapeutic concentrations.
99% bound primarily to albumin
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.
0.1-0.2 L/kg, indicating low tissue distribution; predominantly confined to plasma and extracellular fluid.
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.
Oral: 80-100% (immediate-release), 70-90% (extended-release); Topical: approximately 5-10% systemic absorption; Intravenous: 100%.
GFR 30-89 m L/min: No adjustment needed. GFR <30 m L/min: Avoid use due to ibuprofen component. Hemodialysis: Not recommended.
Cr Cl >30 m L/min: no adjustment. Cr Cl 10-30 m L/min: 200 mg every 12 hours; avoid if Cr Cl <10 m L/min.
Child-Pugh A: No adjustment. Child-Pugh B: Reduce oxycodone dose by 50% (e.g., consider alternative). Child-Pugh C: Avoid use (contraindicated).
Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or avoid. Child-Pugh C: contraindicated due to risk of hepatotoxicity.
Not approved for pediatric use; safety and efficacy not established in patients <18 years.
6 months to 12 years: 5-10 mg/kg/dose every 6-8 hours; max 40 mg/kg/day. For juvenile idiopathic arthritis: 30-40 mg/kg/day divided every 6-8 hours; max 50 mg/kg/day.
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.
Initiate at lowest effective dose; consider 200 mg every 8-12 hours; monitor renal function and GI bleeding risk.
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.
NSAIDs cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may increase with duration of use. Contraindicated for treatment of peri-operative pain in coronary artery bypass graft (CABG) surgery.
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.
Cardiovascular thrombotic events,Gastrointestinal bleeding, ulceration, and perforation,Hypertension,Heart failure exacerbation,Renal toxicity,Anaphylactic reactions,Serious skin reactions (e.g., Stevens-Johnson syndrome),Hematologic effects (anemia, bleeding)
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.
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs,Peri-operative pain in CABG surgery,Active gastrointestinal bleeding,Advanced renal disease,Third trimester of pregnancy
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.
Ibuprofen can increase the risk of stomach bleeding when taken with alcohol. No specific food restrictions, but taking with food or milk can reduce GI irritation.
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.
First and second trimester: Increased risk of miscarriage and congenital malformations (particularly cardiac defects) associated with NSAID use. Third trimester: Known risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment; contraindicated after 30 weeks gestation.
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.
Ibuprofen is excreted into breast milk in low concentrations (M/P ratio approximately 0.01-0.03). Considered compatible with breastfeeding by the American Academy of Pediatrics; use lowest effective dose for shortest duration.
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.
Increased plasma volume and renal clearance in pregnancy may reduce drug levels; however, no standard dose adjustment recommended. Use lowest effective dose, avoid in third trimester.
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.
Ibuprofen is a nonselective COX inhibitor with anti-inflammatory, analgesic, and antipyretic effects. Avoid in patients with aspirin allergy, active peptic ulcer, or severe renal impairment. Use lowest effective dose for shortest duration to minimize GI and cardiovascular risks. Not recommended in patients with advanced chronic kidney disease (e GFR <30 m L/min/1.73 m²). For acute pain, ibuprofen 200-400 mg every 6 hours PRN. Monitor for signs of GI bleeding, hypertension, and fluid retention.
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.
Take with food or milk to reduce stomach upset.,Do not exceed 1200 mg per day unless directed by your doctor.,Avoid alcohol while taking this medication.,Stop use and seek medical help if you experience chest pain, weakness, slurred speech, or signs of stomach bleeding (black/tarry stools, vomit that looks like coffee grounds).,Do not take with other NSAIDs or aspirin without consulting your healthcare provider.
No interactions on record
"Concomitant use of Ibuprofen (a nonsteroidal anti-inflammatory drug, NSAID) and Methylprednisolone (a systemic corticosteroid) synergistically increases the risk of gastrointestinal (GI) ulceration, bleeding, and perforation due to additive inhibition of prostaglandin synthesis and mucosal protection. Additionally, Ibuprofen may potentiate the immunosuppressive effects of Methylprednisolone, elevating infection risk. This interaction can lead to serious clinical outcomes, including acute GI hemorrhage, perforation, and impaired wound healing."
"The combination of olopatadine, an antihistamine with sedative properties, and ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), may result in additive central nervous system (CNS) depression, leading to increased sedation, dizziness, and impaired psychomotor function. Ibuprofen can inhibit the metabolism of olopatadine via competition for hepatic CYP450 enzymes, potentially elevating olopatadine plasma concentrations and prolonging its systemic effects. Clinically, patients may experience exacerbated drowsiness, reduced alertness, and increased risk of falls or accidents, especially in the elderly or those with compromised hepatic function."
"Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), can decrease the metabolism of pioglitazone, a thiazolidinedione antidiabetic agent, by inhibiting cytochrome P450 2C8 (CYP2C8) enzyme activity. This inhibition elevates plasma concentrations of pioglitazone, potentially enhancing its hypoglycemic effects and increasing the risk of adverse reactions such as edema, weight gain, and heart failure exacerbation. Clinically, concomitant use may lead to improved glycemic control but also raises concerns for dose-dependent toxicities, necessitating careful monitoring and possible dose adjustment of pioglitazone."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about COMBUNOX vs IBU, answered by our medical review team.
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.. IBU is a Nonsteroidal Anti-inflammatory Drug (NSAID) that works by Non-selective inhibitor of cyclooxygenase (COX-1 and COX-2), decreasing prostaglandin synthesis, thereby reducing inflammation, pain, and fever.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between COMBUNOX and IBU 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 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.. The standard adult dose of IBU is: 200-800 mg orally every 6-8 hours as needed; maximum 3200 mg/day. For OTC use: 200-400 mg every 4-6 hours; max 1200 mg/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 COMBUNOX and IBU 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. 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. IBU is classified as Category C. First and second trimester: Increased risk of miscarriage and congenital malformations (particularly cardiac defects) associated with NSAID use. Third trimester: Known risk of prem. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.