Dosing and uses of Combunox (oxycodone/ibuprofen)
Adult dosage forms and strengths
oxycodone/ibuprofen
tablet: Schedule II
- 5mg/400mg
Analgesia
Indicated for short-term management of acute, moderate to severe pain
Use lowest effective dose for the shortest duration consistent with individual patient treatment goals
Usual dose: 5 mg/400 mg PO q6 hr PRn
Dosage should not exceed 20 mg/1600 mg (4 tablets) q24 h and should not exceed 7 days duration
Renal Impairment
Not recommended in patients with advanced renal disease
Administration
Not indicated for the treatment of chronic conditions such as osteoarthritis or rheumatoid arthritis
Use extra caution and reduced dosages when treating the elderly or debilitated patients; increased risk of gastrointestinal injury, including fatal events; increased risk of renal toxicity and injury; respiratory depression may occur
Pediatric dosage forms and strengths
Safety and efficacy not established
Combunox (oxycodone/ibuprofen) adverse (side) effects
>10%
Dizziness (5-19%)
Drowsiness (7-17%)
Nausea (9-25%)
1-10%
Constipation (1-5%)
Diarrhea (2%)
Dyspepsia (1-2%)
Flatulence (1%)
Hypotension (1-3%)
Vomiting (5%)
Headache (10%)
Fever (3%)
Diaphoresis (2%)
Weakness (1-3%)
<1%
Anemia
Pharyngitis
Urinary retention
Syncope
Hyperkinesias
Chest pain
Amblyopia
Hypokalemia
Thrombophlebitis
Warnings
Black box warnings
Cardiovascular Risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
- Risk may increase with duration of use
- Patients with risk factors for or existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke)
Gastrointestinal Risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal
- GI adverse events may occur at any time during use and without warning symptoms
- Elderly patients are at greater risk for serious GI events
Contraindications
Coronary artery bypass graft (CABG) surgery, treatment of peri-operative pain; increased incidence of myocardial infarction and stroke
Hypersensitivity to ibuprofen, other NSAIDs, oxycodone, or any component of the formulation
ASA allergy
Acute or severe bronchial asthma
Significant respiratory depression
Hypercarbia
Cautions
Cardiovascular event risk may increase with duration of use
Gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal may occur
Abuse, misuse, diversion, and dependence potentiaL
Respiratory depression may occur
Alcohol use or smoking; increased risk of gastrointestinal injury
Asthma, especially with history of aspirin-sensitive asthma; severe bronchospasm and fatalities may occur
Coagulation disorder; bleeding time may be prolonged
Long-term use; increased risk of gastrointestinal or renal injury; anemia may occur
Use may increase risk of hyperkalemia
Pregnancy, third trimester use; premature close of ductus arteriosus may occur
Skin reactions; serious adverse events including exfoliative dermatitis, Stevens Johnson syndrome, toxic epidermal necrolysis
May mask diagnosis of acute abdominal conditions; use caution
Use caution in adrenal insufficiency, aseptic meningitis, asthma, biliary tract impairment, patients with CNS depression or coma, history of drug abuse, head injury, severe hepatic impairment, hypertension, obesity, prostatic hyperplasia, psychosis, respiratory disease, thyroid dysfunction, renal impairment, or seizures
Pregnancy and lactation
Pregnancy category: C <30 weeks gestation; category D if 30 weeks gestation or greater because of potential for NSAIDs to cause premature closure of the ductus arteriosus
Lactation: Oxycodone excreted in breast milk, effect on infant unknown; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Combunox (oxycodone/ibuprofen)
Half-Life
Oxycodone: 3-4.5 hr
Ibuprofen: 2-4 hr
Duration
Oxycodone: 3-6 hr
Ibuprofen: 4-6 hr
Onset
Oxycodone: 10-15 min
Ibuprofen: 0.5 hr
Absorption
Oxycodone: 100% bioavailability
Ibuprofen: 80-90% bioavailability
Peak Plasma Time
Oxycodone: 0.5-1 hr
Ibuprofen: 2 hr
Protein Bound
Ibuprofen 90-99%
Metabolism
Oxycodone: by liver hepatic P450 enzyme CYP2D6 active prodrug and metabolite
Ibuprofen: rapid hepatic oxidation to inactive metabolites
Metabolites: noroxycodone, oxymorphone (and their glucuronide conjugates)
Pharmacogenomics
Oxycodone is metabolized to oxymorphone via CYP2D6; CYP2D6 poor metabolizers may not achieve adequate analgesia
Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion
Mechanism of action
Fixed combination tablet combines the opioid analgesic agent, oxycodone HCl, with the nonsteroidal anti- inflammatory (NSAID) agent, ibuprofen
Oxycodone: Binds to opiate receptors within neuronal membranes of synapses, which in turn blocks pain perception in the cerebral cortex; inhibits the flow of pain sensations into the higher centers
Ibuprofen: Inhibits synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) & -2 (COX-2)
