OXYCODONE HYDROCHLORIDE AND IBUPROFEN

Clinical safety rating: avoid

Positive evidence of fetus risks but benefits may outweigh risks in some cases

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.

Breastfeeding

Oxycodone excreted in breast milk; M/P ratio approximately 1.1. Ibuprofen excreted in low levels (M/P <0.01). American Academy of Pediatrics considers both compatible with breastfeeding; however, monitor infant for sedation, respiratory depression, and poor feeding due to oxycodone.

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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	Constipation
Serious Effects

Absolute Contraindications

Significant respiratory depression; acute or severe bronchial asthma; known or suspected gastrointestinal obstruction; hypersensitivity to oxycodone, ibuprofen, or any component; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; in the setting of coronary artery bypass graft (CABG) surgery.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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