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Dear Readers! I started this blog when my daughter was in the NICU. She had ventriculitis. Her CSF report grew E.coli. But, she was injected Teicoplanin directly into her brain. The doctors made two errors here:

Teicoplanin is for gram-positive bacteria only. It does not treat E.coli.
Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

My daughter bled into the brain. She lived for another two years and ultimately died.

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Combunox (Oxycodone and Ibuprofen) - Uses, Dose, Side effects, MOA

Combunox (Oxycodone and Ibuprofen) is a combination of an opioid analgesic and a commonly used anti-inflammatory drug. It is used in the treatment of moderate to severe pain.

Combunox (Oxycodone and Ibuprofen) Uses:

Pain:
- managing acute to moderate pain for a brief period (7 days) when it is severe enough to require opioid medication and when no other kind of treatment is effective.
- Limitations of use: Use oxycodone/ibuprofen exclusively in individuals for whom no other therapy choices [such as non-opioid analgesics] have been tolerated or are not anticipated to be tolerated and do not give enough analgesia.

Combunox (Oxycodone and Ibuprofen) Dose in Adults

Combunox (Oxycodone and Ibuprofen) Dose in the treatment of Pain:

Oral: If necessary, take one tablet of oxycodone 5 mg and 400 mg of ibuprofen every six hours (the maximum dosage is oxycodone 20 mg and 1,600 mg [four tablets] per 24 hours); do not take for longer than seven days.

Use in Children:

Refer to adults dosing.

Pregnancy Risk Factor C/D ≥30 weeks' gestation

Binds to the CNS opiate receptors, inhibiting ascending pain pathways, and altering perception of pain.

[US Boxed Warning]Neonatal withdrawal syndrome can be caused by prolonged opioid use during pregnancy.
If not treated, it could prove fatal. Pregnant women who are on opioid therapy should be aware that they have options and to inform their doctor about the risk to the newborn.
Long-term opioid abuse can lead to secondary hypogonadism. This may result in infertility or sexual dysfunction in both men as well as women.

Use of oxycodone or ibuprofen while breastfeeding

Breast milk contains oxycodone and Ibuprofen.
According to the manufacturer of the product, when deciding whether to continue or stop breastfeeding during therapy, it should consider the risks to infant exposure, the benefits to the infant and the benefits to the mother.

Dose in Kidney Disease:

No dosage adjustments provided by manufacturer’s labeling (has not been studied). Avoid use in advanced renal disease.

Dose in Liver Disease:

No dosage adjustments provided in the manufacturer’s labeling (has not been studied); use cautiously in severe impairment.

Common Side Effects of Combunox (Oxycodone and Ibuprofen):

Central nervous system:
- Dizziness
- Drowsiness
Gastrointestinal:
- Nausea

Less Common Side Effects of Combunox (Oxycodone and Ibuprofen):

Cardiovascular:
- Vasodilation
Central Nervous System:
- Headache
Gastrointestinal:
- Vomiting
- Constipation
- Diarrhea
- Dyspepsia
- Flatulence
Neuromuscular & Skeletal:
- Weakness
Miscellaneous:
- Fever

Contraindications to Combunox (Oxycodone and Ibuprofen):

Hypersensitivity to oxycodone, ibuprofen, other opioids, or any component of the formulation;
Paralytic ileus (known and suspected);
In the setting of coronary bypass graft surgery (CABG);
Respiratory depression is a serious problem
Hypercarbia or acute bronchial asthma, in unmonitored settings or without resuscitative devices
Histories of asthma
Urticaria or other allergic reactions following aspirin use or other NSAIDs.

Warnings and precautions

Anaphylactoid reactions
- Even in patients who have never been exposed, anaphylactoid reactions can occur.
- Patients with the "aspirine trifecta" (bronchial asthma and aspirin intolerance, rhinitis, etc.) could be at greater risk.
- Patients with rhinitis or NSAID therapy, such as bronchospasm or asthma, should not use this medication.
Cardiovascular events: [US Boxed Warn]
- There is a higher risk of severe (and possibly fatal) adverse cardiovascular events due to NSAIDs, such as stroke and fatal MI.
- The risk of developing complications early in treatment may be increased with prolonged use.
- The relative risk seems to be the same for those with and without cardiovascular disease, or risk factors for it.
- However, the absolute incidence of serious cardiovascular events (which can occur early in treatment) was higher among patients with cardiovascular disease and those who received higher doses.
- Exacerbation or new onset hypertension could occur (NSAIDs can also impair the response to ACE inhibitors, thiazide dialuretics or loop diuretics); this may lead to cardiovascular events.
- Monitor blood pressure and use caution in hypertension patients.
- It may cause fluid retention and sodium buildup; caution is advised for patients with edema.
- Avoid using in the event of heart failure.
- If there are any cardiovascular thrombotic risks, it is best to avoid patients who have had a recent MI.
- To reduce the risk of heart attacks, use the lowest effective dose and for the shortest time. Patients at high risk should consider alternate treatments.
CNS depression:
- CNS depression can lead to mental or physical impairments.
- Patients should be aware that driving, operating machinery and other tasks that require mental alertness may put them at risk.
Constipation
- Patients with unstable angina or post-myocardial injury may experience constipation from Oxycodone.
- To reduce constipation, consider preventive measures such as stool softener or increased fiber.
GI events: [US Boxed Warning]
- NSAIDs can increase the risk of serious GI inflammation, ulceration and bleeding (may be fatal); patients older than 65 years old and those with a history of peptic ulcer disease or GI bleeding are more at risk. These events can occur at any time, and may not be predicted.
- Patients with active GI bleeding should be avoided. Avoid non-aspirin NSAIDs in patients who have had a history or experience of severe lower GI bleeding.
- Be cautious if you have a history of GI problems, and are taking concurrent therapies that can increase your risk of GI bleeding, such as anticoagulants and/or steroids, selective serotonin reuptake inhibits, aspirin, corticosteroids and/or anticoagulants, advanced hepatic diseases, smoking, alcohol use, or in elderly patients or those with severe disabilities.
- To lower the risk of GI adverse reactions, use the lowest effective dose and for as short a time as possible. Patients at high risk should consider alternate treatments.
- Concomitant use of aspirin can lead to a significant increase in the risk for GI complications (eg ulcers).
- Consequently, it is advised to use concomitant gastroprotective medication (such as proton pump inhibitors).
Hematologic effects
- The adhesion or aggregation of platelets may be reduced by NSAIDs. A protracted bleeding period could result from this.
- Anticoagulant users and patients with coagulation problems require close observation.
- Patients undergoing long-term NSAID medication for anaemia should be constantly watched since anaemia can arise.
- Occasionally have severe blood problems been connected to NSAID use (eg, thrombocytopenia or agranulocytosis).
Hepatic effects
- Patients with abnormal LFT have had transaminase levels reported.
- Rare, sometimes fatal, severe hepatic reactions have been reported. If you notice any signs or symptoms of hepatic diseases, discontinue use immediately.
Hyperkalemia:
- NSAIDs may increase hyperkalemia risk in patients with kidney disease, elderly patients, diabetics, and those who have used ACE inhibitors or other agents that can cause hyperkalemia. Pay attention to potassium.
Hypotension
- Oxycodone can cause severe hypotension, including orthostatic hypotension or syncope.
- Patients with hypovolemia and cardiovascular disease (including acute MI) should be cautious.
- After starting or increasing the dose, be aware of signs and symptoms that could indicate hypotension.
- Individuals who have circulatory shock need to exercise caution.
Phenanthrene hypersensitivity:
- In individuals who have experienced hypersensitivity to other phenanthrene-derivative opioid agonists, use oxycodone with caution (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).
Effects on the renal system:
- NSAIDs can worsen renal dysfunction. Dose-dependent decreases of prostaglandin synthesis could be caused by NSAIDs.
- This may reduce renal blood flow, which can lead to renal decompensation (usually reversible).
- Patients with impaired renal function, hypovolemia and heart failure, as well as those who take diuretics and ACE inhibitors, are more at risk for renal toxicity.
- Before initiating treatment, hydrate the patient and monitor their renal function.
- Long-term NSAID treatment may cause renal papillary necrosis or other injury.
Respiratory depression [US Boxed Warning]
- Oxycodone/ibuprofen may cause severe, life-threatening or fatal respiratory depression.
- Be on the lookout for signs of respiratory depression during treatment or after a dose increase.
- The sedating effects that opioids can cause in the respiratory tract is known as opioid-induced respiratory depression.
Reactions to skin:
- NSAIDs can cause serious and potentially fatal skin adverse events, including exfoliative dermatitis (SJS), Stevens-Johnson syndromes (SJS) or toxic epidermal necrolysiss (TEN).
- These may occur without warning. Stop using NSAIDs at the first sign of skin rash or any other signs of hypersensitivity.
Conditions abdominales:
- Patients with acute abdominal conditions may be misdiagnosed or treated with Oxycodone.
Adrenocortical Insufficiency
- Patients with adrenocortical impairment, such as Addison disease, should be cautious when taking oxycodone.
- Long-term opioid abuse can lead to secondary hypogonadism. This could cause infertility, sexual dysfunction, mood disorders, and osteoporosis.
Aseptic meningitis
- Aseptic meningitis can be caused by NSAIDs, particularly in patients with SLE and mixed connective tissue disorders.
Asthma
- Patients with asthma that is aspirin-sensitive should not take NSAIDs. They may experience severe, potentially fatal bronchospasm.
- Patients with other forms or asthma should be cautious.
Bariatric surgery
- After bariatric surgery, avoid using oral nonselective NSAIDs on a regular basis since this may lead to anastomotic ulcerations or perforations.
- Celecoxib or IV ketorolac should be used briefly as part of a multimodal pain management plan to treat postoperative pain.
Insufficiency of the biliary tract:
- Patients with biliary dysfunction and acute pancreatitis should be cautious when taking oxycodone.
- Oxycodone may cause constriction of the sphincter. This can lead to reduced biliary secretions.
CNS depression/coma:
- Patients with CNS depression and coma should not be given oxycodone. These patients are more susceptible to the intracranial effects CO2 retention.
Coronary bypass surgery for coronary artery bypass: [US Boxed Warn]
- In the context of coronary bypass graft surgery (CABG), it is not recommended to use. Use of CABG surgery may increase your risk of stroke and MI.
Delirium tremens:
- Patients with delirium-tremens should be cautious when taking oxycodone.
Head trauma
- Patients with intracranial injuries, intracranial lesions or elevated intracranial pressures (ICP) should be cautious when using oxycodone. A marked increase in ICP could occur.
Hepatic impairment
- Patients with severe hepatic impairment should be cautious; patients suffering from advanced hepatic disease may experience GI bleeding when using NSAIDs.
Obesity:
- Patients who are severely obese should not take oxycodone.
Prostatic hyperplasia/urinary restriction:
- Patients with urinary stricture or prostatic hyperplasia should not take oxycodone.
Psychosis:
- Patients with toxic psychosis should be cautious when taking oxycodone.
Renal impairment
- Patients with advanced renal disease should not be given NSAIDs.
Respiratory disease
- Patients with severe chronic obstructive lung disease (or cor pulmonale) should be cautious when using oxycodone.
- Moreover, individuals who have hypoxia, a drastically reduced respiratory reserve, or a history of respiratory depression should be closely watched.
- You might consider using non-opioid analgesics for these patients.
Seizures:
- Patients with seizure disorders should be cautious when taking oxycodone. It may worsen or cause seizures.
Thyroid dysfunction:
- Patients with thyroid dysfunction should be cautious when taking oxycodone.

Oxycodone and ibuprofen: Drug Interaction

Risk Factor C (Monitor therapy)
5-Aminosalicylic Acid Derivatives	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
Aliskiren	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction.
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Aminoglycosides	Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
Aminolevulinic Acid (Topical)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical).
Amphetamines	May enhance the analgesic effect of Opioid Agonists.
Angiotensin II Receptor Blockers	May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function.
Angiotensin-Converting Enzyme Inhibitors	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors.
Anticholinergic Agents	May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination.
Anticoagulants	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.
Anticoagulants	Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Beta-Blockers	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol.
Bisphosphonate Derivatives	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern.
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Cephalothin	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Collagenase (Systemic)	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
Corticosteroids (Systemic)	May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents (Nonselective).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased.
Dasatinib	May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Deferasirox	Nonsteroidal Anti-Inflammatory Drugs may intensify Deferasirox's negative/toxic effects. Particularly, there may be a higher risk of GI bleeding or ulcers.
Deoxycholic Acid	Deoxycholic Acid's harmful or toxic effects may be increased by substances with antiplatelet properties. In particular, there may be a higher chance of bleeding or bruising in the treatment region.
Desmopressin	Nonsteroidal Anti-Inflammatory Drugs may intensify Desmopressin's harmful or toxic effects.
Desmopressin	Opioid antagonists may intensify Desmopressin's harmful or hazardous effects.
Digoxin	Nonsteroidal Anti-Inflammatory Drugs may raise the level of digoxin in the blood.
Dimethindene (Topical)	CNS depressants may have an enhanced CNS depressant impact.
Diuretics	Opioid antagonists might make diuretics' harmful or toxic effects worse. Opioid antagonists may reduce diuretics' therapeutic benefit.
Dronabinol	CNS depressants may have an enhanced CNS depressant impact.
Drospirenone	Nonsteroidal Anti-Inflammatory Drugs may intensify Drospirenone's hyperkalemic impact.
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Eplerenone	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fat Emulsion (Fish Oil Based)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Felbinac	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Gastrointestinal Agents (Prokinetic)	Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).
Glucosamine	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
HydrALAZINE	Nonsteroidal Anti-Inflammatory Drugs may lessen HydrALAZINE's ability to lower blood pressure.
Ibritumomab Tiuxetan	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding.
Ibrutinib	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Inotersen	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Limaprost	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Multivitamins/Fluoride (with ADE)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with AE, No Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Naftazone	May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Obinutuzumab	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
Omega-3 Fatty Acids	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Pegvisomant	Opioid Agonists may diminish the therapeutic effect of Pegvisomant.
Pentosan Polysulfate Sodium	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents.
Pentoxifylline	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Piribedil	CNS Depressants may enhance the CNS depressant effect of Piribedil.
Porfimer	Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
Potassium-Sparing Diuretics	Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics.
PRALAtrexate	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation.
Pramipexole	CNS Depressants may enhance the sedative effect of Pramipexole.
Probenecid	May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents.
Prostacyclin Analogues	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Prostaglandins (Ophthalmic)	Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic).
Quinolones	Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones.
Ramosetron	Opioid Agonists may enhance the constipating effect of Ramosetron.
RifAMPin	May decrease the serum concentration of OxyCODONE.
ROPINIRole	CNS Depressants may enhance the sedative effect of ROPINIRole.
Rotigotine	CNS Depressants may enhance the sedative effect of Rotigotine.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Salicylates	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Serotonin Modulators	Opioid Agonists may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.
Serotonin/Norepinephrine Reuptake Inhibitors	May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
St John's Wort	May decrease the serum concentration of OxyCODONE.
Succinylcholine	May enhance the bradycardic effect of Opioid Agonists.
Tacrolimus (Systemic)	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic).
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Thiazide and Thiazide-Like Diuretics	May enhance the nephrotoxic effect of Nonsteroidal AntiInflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics.
Thrombolytic Agents	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
Tipranavir	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Tolperisone	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents.
Vancomycin	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin.
Verteporfin	Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
Vitamin E (Systemic)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Risk Factor D (Consider therapy modification)
Alvimopan	Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation.
Apixaban	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Bemiparin	Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.
Bemiparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.
Bile Acid Sequestrants	May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
CNS Depressants	May enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
CycloSPORINE (Systemic)	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs.
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
CYP3A4 Inhibitors (Strong)	May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased.
Dabigatran Etexilate	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Diclofenac (Systemic)	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs.
Droperidol	May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Edoxaban	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Enoxaparin	Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.
Enoxaparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Flunitrazepam	Flunitrazepam's CNS depressing effects may be enhanced by other CNS depressants.
Heparin	The anticoagulant effect of heparin may be enhanced by nonsteroidal anti-inflammatory drugs. If coadministration is necessary, reduce the dosage of heparin or nonsteroidal anti-inflammatory drugs (NSAIDs).
Heparin	The anticoagulant effect of heparin may be strengthened by substances with antiplatelet properties. If coadministration is necessary, reduce the dose of heparin or other medications with antiplatelet characteristics.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	Agents with poisonous or harmful effects may intensify their negative or hazardous effects. Bleeding could happen. Management: Where at all possible, avoid combining. If used, keep a closer eye out for signs of bleeding. Two weeks before any type of surgery, dental work, or invasive procedure, stop using herbal remedies that have anticoagulant or antiplatelet effects.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	Nonsteroidal Anti-Inflammatory Agents may intensify their negative or harmful effects. Bleeding could happen.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Imatinib	Ibuprofen may decrease the serum concentration of Imatinib. Specifically, ibuprofen may decrease intracellular concentrations of imatinib, leading to decreased clinical response. Management: Consider using an alternative to ibuprofen in patients who are being treated with imatinib. Available evidence suggests other NSAIDs do not interact in a similar manner.
Lithium	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium.
Loop Diuretics	Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Methotrexate	Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Monoamine Oxidase Inhibitors	OxyCODONE may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Seek alternatives when possible. Avoid use of oxycodone/naltrexone during and within 14 days after monoamine oxidase inhibitor treatment. Non-US labeling for some oxycodone products states that such use is contraindicated.
Nalmefene	May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of nalmefene and opioid agonists. Discontinue nalmefene 1 week prior to any anticipated use of opioid agonistss. If combined, larger doses of opioid agonists will likely be required.
Naltrexone	May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations.
PEMEtrexed	The serum levels of PEMEtrexed may rise in response to ibuprofen. Treatment: Patients should abstain from ibuprofen for 2 days prior to, the day of, and 2 days after the administration of pemetrexed. This applies to patients with an estimated creatinine clearance of 45 to 79 mL/min. If coupled, keep an eye out for increased pemetrexed toxicity.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
PHENobarbital	May enhance the CNS depressant effect of OxyCODONE. PHENobarbital may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined.
Primidone	May enhance the CNS depressant effect of OxyCODONE. Primidone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined.
Rivaroxaban	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
Salicylates	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Exceptions: Choline Magnesium Trisalicylate.
Selective Serotonin Reuptake Inhibitors	May enhance the antiplatelet effect of Nonsteroidal AntiInflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk.
Sincalide	Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Sodium Phosphates	May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Tenofovir Products	Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose.
Vitamin K Antagonists (eg, warfarin)	Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists.
Voriconazole	May enhance the adverse/toxic effect of OxyCODONE. Voriconazole may increase the serum concentration of OxyCODONE. Management: A reduced oxycodone dose may be necessary with concurrent voriconazole. Increased frequency and duration of monitoring for oxycodone-related adverse effects is recommended.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.
Risk Factor X (Avoid combination)
Acemetacin	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Aminolevulinic Acid (Systemic)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Dexibuprofen	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Dexibuprofen.
Dexketoprofen	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Eluxadoline	Opioid Agonists may enhance the constipating effect of Eluxadoline.
Floctafenine	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ketorolac (Nasal)	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Ketorolac (Systemic)	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Macimorelin	Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin.
Mifamurtide	Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide.
Morniflumate	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective)	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective).
Omacetaxine	Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL.
Opioids (Mixed Agonist / Antagonist	May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pelubiprofen	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Phenylbutazone	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Talniflumate	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Tenoxicam	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Urokinase	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase.
Zaltoprofen	May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.

Monitoring Parameters:

Respiratory function
blood pressure
CBC
chemistry profile
occult blood loss
periodic liver function tests
renal function (urine output, serum BUN and creatinine)
gastrointestinal effects (abdominal pain, bleeding, dyspepsia)
mental confusion, disorientation
signs or symptoms of hypogonadism or hypoadrenalism (Brennan, 2013).

How to administer Combunox (Oxycodone and Ibuprofen)?

Administer with or without meals.

Mechanism of action of Combunox (Oxycodone and Ibuprofen):

Oxycodone:

Binds to opiate receptors in the central nervous system (CNS), inhibiting ascending pain pathways, changing how people perceive and react to pain, and resulting in generalised CNS depression.

Ibuprofen:

Inhibits cyclooxygenase-1 (COX-1) and 2 (COX-2) enzymes in a way that can be reversed. This leads to the formation of prostaglandin precursors. It has antipyretic and analgesic properties.

Also see individual agents.

Absorption:

Rapidly absorbed

Time to peak, serum:

Ibuprofen: 1.6 to 3.1 hours; Oxycodone 1.3 to 2.1 hours

Oxycodone and Ibuprofen Interantional Brand Names:

Combunox

Oxycodone and ibuprofen Brands Names in Pakistan:

No Brands Available in Pakistan.

Disclaimer Notice:

Emedz.net is not an online pharmacy:

We are not affiliated with any pharmaceutical companies:

Combunox (Oxycodone and Ibuprofen) - Uses, Dose, Side effects, MOA

Combunox (Oxycodone and Ibuprofen) Uses:

Pain:

Combunox (Oxycodone and Ibuprofen) Dose in Adults

Combunox (Oxycodone and Ibuprofen) Dose in the treatment of Pain:

Use in Children:

Pregnancy Risk Factor C/D ≥30 weeks' gestation

Use of oxycodone or ibuprofen while breastfeeding

Dose in Kidney Disease:

Dose in Liver Disease:

Common Side Effects of Combunox (Oxycodone and Ibuprofen):

Central nervous system:

Gastrointestinal:

Less Common Side Effects of Combunox (Oxycodone and Ibuprofen):

Cardiovascular:

Central Nervous System:

Gastrointestinal:

Neuromuscular & Skeletal:

Miscellaneous:

Contraindications to Combunox (Oxycodone and Ibuprofen):

Warnings and precautions

Anaphylactoid reactions

Cardiovascular events: [US Boxed Warn]

CNS depression:

Constipation

GI events: [US Boxed Warning]

Hematologic effects

Hepatic effects

Hyperkalemia:

Hypotension

Phenanthrene hypersensitivity:

Effects on the renal system:

Respiratory depression [US Boxed Warning]

Reactions to skin:

Conditions abdominales:

Adrenocortical Insufficiency

Aseptic meningitis

Asthma

Bariatric surgery

Insufficiency of the biliary tract:

CNS depression/coma:

Coronary bypass surgery for coronary artery bypass: [US Boxed Warn]

Delirium tremens:

Head trauma

Hepatic impairment

Obesity:

Prostatic hyperplasia/urinary restriction:

Psychosis:

Renal impairment

Respiratory disease

Seizures:

Thyroid dysfunction:

Monitoring Parameters:

How to administer Combunox (Oxycodone and Ibuprofen)?

Mechanism of action of Combunox (Oxycodone and Ibuprofen):

Oxycodone and Ibuprofen Interantional Brand Names:

Oxycodone and ibuprofen Brands Names in Pakistan:

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