OXYCODONE HYDROCHLORIDE AND IBUPROFEN
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Oxycodone is a full mu-opioid receptor agonist, leading to analgesia, euphoria, and sedation. Ibuprofen inhibits cyclooxygenase (COX)-1 and COX-2, reducing prostaglandin synthesis and providing analgesic, anti-inflammatory, and antipyretic effects.
| Metabolism | Oxycodone is metabolized primarily via CYP3A4 and CYP2D6 to active metabolites (noroxycodone, oxymorphone). Ibuprofen is metabolized via CYP2C9 and CYP2C8 to inactive metabolites. |
| Excretion | Oxycodone: primarily renal (87%) as metabolites, with ~19% unchanged; Ibuprofen: renal (90%) as metabolites, with ~10% unchanged; small biliary/fecal elimination for both. |
| Half-life | Oxycodone: 3-5 hours; Ibuprofen: 1.8-2.5 hours. Clinical context: Oxycodone's half-life allows dosing every 4-6 hours; Ibuprofen's shorter half-life supports frequent dosing for sustained anti-inflammatory effect. |
| Protein binding | Oxycodone: ~45% bound to albumin; Ibuprofen: >99% bound to albumin. |
| Volume of Distribution | Oxycodone: Vd 2.0-3.0 L/kg (high tissue distribution: CNS, muscle); Ibuprofen: Vd 0.1-0.2 L/kg (limited to plasma and extracellular fluid). |
| Bioavailability | Oral: Oxycodone 60-87% (higher with repeated dosing due to saturation of first-pass); Ibuprofen 80-100% (rapidly absorbed). |
| Onset of Action | Oral: Oxycodone onset 10-15 minutes, ibuprofen onset 30-60 minutes. Maximum effect: oxycodone 0.5-1 hour, ibuprofen 1-2 hours. |
| Duration of Action | Oxycodone: 4-6 hours; Ibuprofen: 4-6 hours. Clinical note: Duration sufficient for acute pain; extended relief requires combination or controlled-release formulations. |
| Molecular Weight | 408.49 |
One tablet containing oxycodone hydrochloride 5 mg and ibuprofen 400 mg orally every 6 hours as needed for pain; maximum 4 tablets per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: No adjustment recommended. GFR 15-29 mL/min: Use with caution; consider reducing dose or extending interval; avoid use in severe renal impairment (GFR <30 mL/min) due to risk of ibuprofen accumulation and nephrotoxicity. GFR <15 mL/min: Not recommended. |
| Liver impairment | Child-Pugh Class A (mild): No adjustment recommended. Child-Pugh Class B (moderate): Use with caution; reduce starting dose of oxycodone by 50% (e.g., half tablet) and monitor; ibuprofen should be avoided or used at lowest effective dose. Child-Pugh Class C (severe): Contraindicated due to risk of hepatic encephalopathy and bleeding. |
| Pediatric use | Not approved in children <18 years of age. For weight-based dosing in adolescents (≥18 years): same as adult based on oxycodone component 0.05-0.15 mg/kg/dose (max 5 mg) and ibuprofen 5-10 mg/kg/dose (max 400 mg) every 6 hours as needed; not to exceed 4 doses per day. |
| Geriatric use | Start at lowest effective dose (one-half tablet every 6 hours) due to increased sensitivity to opioids (respiratory depression, constipation) and NSAID-related GI/renal risks; monitor renal function and for cognitive impairment; maximum 4 tablets per day. |
| 1st trimester | Avoid; NSAIDs are associated with increased risk of miscarriage and congenital malformations, particularly cardiac defects, in first trimester. Opioid use may cause neural tube defects, though data are limited. |
| 2nd trimester | Avoid unless benefit outweighs risk; NSAIDs may cause oligohydramnios and fetal renal impairment. Opioid use may lead to fetal dependence and neonatal abstinence syndrome. |
| 3rd trimester | Avoid; NSAIDs can cause premature closure of ductus arteriosus, oligohydramnios, and fetal renal impairment. Opioid use significantly increases risk of neonatal respiratory depression and withdrawal. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| Placental transfer | Both oxycodone and ibuprofen cross the placenta. Oxycodone achieves fetal plasma concentrations 1-2 times maternal levels. Ibuprofen crosses at low levels (10-20% of maternal concentration), but may accumulate with prolonged use. |
| Breastfeeding |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of just one dose, especially by children, can be fatal; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity due to ibuprofen.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to oxycodone, ibuprofen, or any component of the formulationSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusGastrointestinal obstructionActive peptic ulcer disease or GI bleedingSevere hepatic impairmentSevere renal impairment (CrCl <30 mL/min)Cerebrovascular bleeding or other bleeding disordersConcurrent use of MAO inhibitors or within 14 daysCoronary artery bypass graft (CABG) surgery perioperative painThird trimester pregnancy (due to NSAID effects on ductus arteriosus)
| Precautions | Respiratory depression; addiction potential; interactions with CNS depressants; hepatic impairment; renal toxicity; gastrointestinal bleeding; cardiovascular thrombotic events; adrenal insufficiency; use in elderly; use in pregnancy; breastfeeding. |
Loading safety data…
| Both oxycodone and ibuprofen are excreted into breast milk in low amounts. Ibuprofen is considered safe at recommended doses, but oxycodone may cause infant sedation, respiratory depression, and withdrawal symptoms; monitor for CNS depression. Use lowest effective dose for shortest duration, and consider alternative analgesics when possible. |
| Lactation Rating | L3 - Moderately Safe (oxicodone component) / L1 - Safe (ibuprofen component); overall caution advised due to opioid component. |
| Teratogenic Risk | First trimester: Limited data; opioid use associated with neural tube defects and congenital heart defects in some studies; ibuprofen associated with increased risk of cardiac defects and gastroschisis. Second trimester: Ibuprofen may cause oligohydramnios and premature closure of fetal ductus arteriosus. Third trimester: Prolonged use may cause neonatal opioid withdrawal syndrome; ibuprofen contraindicated due to risk of premature ductus arteriosus closure, oligohydramnios, and fetal nephrotoxicity. |
| Fetal Monitoring | Monitor maternal opioid withdrawal symptoms, respiratory depression, sedation, and pain control. Fetal monitoring: assess for nonstress test, biophysical profile if prolonged use; ultrasound for oligohydramnios and ductus arteriosus patency if ibuprofen used beyond 20 weeks. Neonatal monitoring: observe for neonatal opioid withdrawal syndrome using Finnegan scoring. |
| Fertility Effects | Oxycodone may decrease fertility via hormonal dysregulation (hypogonadotropic hypogonadism) with prolonged use. Ibuprofen may interfere with ovulation and implantation due to prostaglandin inhibition; effects are reversible upon discontinuation. |
| Food/Dietary | Take with food or milk to reduce GI upset. Avoid grapefruit and grapefruit juice (may increase oxycodone levels and risk of adverse effects). Limit alcohol intake due to additive CNS depression and increased GI bleeding risk. |
| Clinical Pearls | Combination product (oxycodone 5 mg/ibuprofen 400 mg) indicated for acute moderate-to-severe pain; limit duration to ≤7 days due to opioid dependence and GI/renal risks; avoid in patients with aspirin/NSAID allergy, asthma, or severe hepatic/renal impairment; monitor for respiratory depression, hypotension, and signs of bleeding; prescribe naloxone for high-risk patients. |
| Patient Advice | 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 drive or operate machinery until you know how this medication affects you. · This drug contains both an opioid and an NSAID; risk of addiction, respiratory depression, and GI bleeding. · Do not take with other NSAIDs (e.g., ibuprofen, naproxen) or acetaminophen-containing products without medical advice. · Swallow tablets whole; do not crush, chew, or dissolve (may cause rapid release and overdose). · Common side effects: constipation, nausea, dizziness, drowsiness; increase fluids and fiber to prevent constipation. · Seek emergency help if you experience trouble breathing, chest pain, severe dizziness, black/tarry stools, or signs of allergic reaction. · Keep out of reach of children and dispose of unused medication via drug take-back program. · Inform all healthcare providers that you are taking this medication before any surgery or procedure. |