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Mechanism of Action
US Drug Names
300 mg PO 4 times daily or 400 to 800 mg PO 3 to 4 times daily. Max: 3,200 mg/day.  
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Max: 800 mg/dose).     Lower dose to smallest effective dose once clinical effect is attained. Patients with milder disease may be adequately treated with 20 mg/kg/day. 
400 mg PO every 4 to 6 hours as needed. Max: 3,200 mg/day.
200 to 400 mg PO every 4 to 6 hours as needed. Max: 1,200 mg/day. Discontinue use if pain gets worse or lasts more than 10 days.
400 to 800 mg IV every 6 hours as needed. Max: 3,200 mg/day.
400 mg IV every 4 to 6 hours as needed. Max: 2,400 mg/day.
10 mg/kg/dose (Max: 400 mg/dose) IV every 4 to 6 hours as needed. Max: 40 mg/kg/day or 2,400 mg/day, whichever is less.
NOTE: Use weight to determine pediatric dosage when possible.
400 mg PO every 4 to 6 hours as needed. Max: 3,200 mg/day. In controlled analgesic clinical trials, doses more than 400 mg were no more effective than the 400 mg dose.
10 mg/kg/dose PO every 6 to 8 hours. Max: 40 mg/kg/day.
200 to 400 mg PO every 4 to 6 hours as needed. Max: 1,200 mg/day.
300 mg PO every 6 to 8 hours as needed. Max: 1,200 mg/day. 
250 mg PO every 6 to 8 hours as needed. Max: 1,000 mg/day. 
200 mg PO every 6 to 8 hours as needed. Max: 800 mg/day. 
150 mg PO every 6 to 8 hours as needed. Max: 600 mg/day. 
100 mg PO every 6 to 8 hours as needed. Max: 400 mg/day. 
75 mg PO every 6 to 8 hours as needed. Max: 300 mg/day.
50 mg PO every 6 to 8 hours as needed. Max: 200 mg/day.
200 to 400 mg PO every 4 to 6 hours as needed. Max: 1,200 mg/day. Discontinue use if fever gets worse or lasts more than 3 days.
300 mg PO every 6 to 8 hours as needed. Max: 1,200 mg/day. Discontinue use if no relief within 24 hours or if fever gets worse or lasts more than 3 days. 
250 mg PO every 6 to 8 hours as needed. Max: 1,000 mg/day. Discontinue use if no relief within 24 hours or if fever gets worse or lasts more than 3 days. 
200 mg PO every 6 to 8 hours as needed. Max: 800 mg/day. Discontinue use if no relief within 24 hours or if fever gets worse or lasts more than 3 days. 
150 mg PO every 6 to 8 hours as needed. Max: 600 mg/day. Discontinue use if no relief within 24 hours or if fever gets worse or lasts more than 3 days. 
100 mg PO every 6 to 8 hours as needed. Max: 400 mg/day. Discontinue use if no relief within 24 hours or if fever gets worse or lasts more than 3 days. 
75 mg PO every 6 to 8 hours as needed. Max: 300 mg/day. Discontinue use if no relief within 24 hours or if fever gets worse or lasts more than 3 days.
50 mg PO every 6 to 8 hours as needed. Max: 200 mg/day. Discontinue use if no relief within 24 hours or if fever gets worse or lasts more than 3 days.
5 to 10 mg/kg/dose PO every 6 to 8 hours. Max: 40 mg/kg/day.
400 mg IV once, then 400 mg IV every 4 to 6 hours or 100 to 200 mg IV every 4 hours as needed. Max: 3,200 mg/day.
20 to 30 mg/kg/dose (Max: 1,600 mg/dose) PO twice daily, initially. Adjust dose to maintain a peak serum concentration of 50 to 100 mcg/mL.   
20 to 30 mg/kg/dose (Max: 1,600 mg/dose) PO twice daily, initially. Adjust dose to maintain a peak serum concentration of 50 to 100 mcg/mL.    Guidelines recommend the chronic use of oral ibuprofen for children 6 to 17 years with cystic fibrosis who have an FEV1 of more than 60% predicted. 
6 mg/kg/dose PO twice daily starting in the field and continuing until frostbite wound is healed or surgical management occurs. Max: 600 mg PO 4 times daily. Guidelines suggest ibuprofen to inhibit harmful prostaglandins, which can cause vasoconstriction, dermal ischemia, and further tissues damage.
200 to 400 mg PO once.  Guidelines classify ibuprofen as having established efficacy for the treatment of acute migraine. 
7.5 to 10 mg/kg/dose (Max: 600 mg/dose) PO once.   Guidelines recommend ibuprofen as an initial treatment option to reduce pain in children and adolescents with migraine.
600 mg PO every 8 hours for 1 to 2 weeks, then decrease dose by 200 to 400 mg/day every 1 to 2 weeks in combination with colchicine.
30 to 50 mg/kg/day PO divided every 8 hours for 1 to 4 weeks. Max: 2.4 g/day. Consider tapering dose gradually every 1 to 2 weeks. 
600 mg PO every 8 hours for at least 2 to 4 weeks, then decrease dose by 200 to 400 mg/day every 1 to 2 weeks in combination with colchicine. Dose range: 1,200 to 2,400 mg/day. 
30 to 50 mg/kg/day PO divided every 8 hours for at least 2 to 4 weeks in combination with colchicine. Max: 2.4 g/day. Consider tapering dose gradually every 1 to 2 weeks. 
3,200 mg/day PO/IV for Rx-only products; 1,200 mg/day PO for non-prescription use.
17 years: 3,200 mg/day PO/IV for Rx-only products; 1,200 mg/day PO for non-prescription use.
13 to 16 years: 50 mg/kg/day PO (Max: 3,200 mg/day) and 2,400 mg/day IV for Rx-only products; 1,200 mg/day PO for non-prescription use.
12 years: 50 mg/kg/day PO (Max: 3,200 mg/day) and 2,400 mg/day IV for Rx-only products; 40 mg/kg/day PO (Max: 1,200 mg/day) for non-prescription use.
1 to 11 years: 50 mg/kg/day PO (Max: 3,200 mg/day) and 40 mg/kg/day IV (Max: 2,400 mg/day) for Rx-only products; 40 mg/kg/day PO (Max: 1,200 mg/day) for non-prescription use.
6 to 11 months: 40 mg/kg/day PO/IV.
1 to 5 months: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Avoid use of ibuprofen in patients with advanced renal disease unless the benefits are expected to outweigh the risks of worsening renal function. If use is necessary, monitor renal function closely. Guidelines recommend the following:
GFR 30 to 59 mL/minute/1.73 m2: Avoid use in patients with intercurrent disease that increases the risk of acute kidney injury. Prolonged therapy is not recommended.GFR less than 30 mL/minute/1.73 m2: Avoid use.
No dosage adjustment is necessary.
Continuous renal replacement therapy (CRRT)
Ibuprofen is an oral and intravenous non-steroidal anti-inflammatory drug (NSAID) indicated for the treatment of mild to severe pain, osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis/juvenile idiopathic arthritis, dysmenorrhea, and fever. All NSAIDs, including ibuprofen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and GI perforation of the esophagus, stomach, small intestine, or large intestine and are associated with an increased risk of serious cardiovascular (CV) thromboembolism, including myocardial infarction or stroke. Use the lowest effective dose for the shortest possible duration; the increase in CV risk has been most consistently observed at higher doses.
For storage information, see the specific product information within the How Supplied section.
The most frequent type of adverse reaction reported with orally administered ibuprofen is gastrointestinal (GI). In controlled trials, the overall incidence of GI adverse reactions associated with oral ibuprofen was about half that seen in aspirin- or indomethacin-treated patients. Severe GI effects occur in patients taking ibuprofen with a frequency of less than 1% and include peptic ulcer (gastric or duodenal ulcer with GI bleeding and/or GI perforation), gastrointestinal hemorrhage, and melena. Inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine can be fatal and may occur at any time, with or without warning symptoms. Only 20% of patients who develop a serious upper GI event is symptomatic. The risk of severe GI events is increased by the presence of the following factors: history of peptic ulcer disease or GI bleed, smoking, alcohol usage, concomitant usage of anticoagulants, or oral corticosteroids, older age, poor general health status, and NSAID duration of use. Upper GI ulcers, gross bleeding, or perforation occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. Gastrointestinal bleeding or erosive gastritis can be minor or life-threatening and may result from a combination of direct irritant action on the stomach mucosa and an increased bleeding time, due to changes in platelet aggregation. Older patients appear to be greater affected by GI ulceration or bleeding; most fatal GI events occur in older or debilitated patients. Occult GI bleeding occurs in many patients and is not necessarily correlated with GI distress. Although the amount of blood lost is usually not significant, patients may become anemic as a result of iron deficiency. Patients on prolonged therapy should undergo regular blood monitoring. Nausea, vomiting, dyspepsia, and flatulence have been reported in 1 to 10% of patients receiving oral ibuprofen and in patients treated with intravenous ibuprofen for post-operative pain at similar rates to those receiving placebo. In pediatric intravenous ibuprofen trials, nausea and vomiting were among the most common adverse events, occurring at an incidence > 2%. Other adverse GI effects reported in 1 to 10% of patients receiving oral ibuprofen include abdominal pain, bloating, constipation, diarrhea, epigastric pain, and pyrosis (heartburn). Abdominal distress, indigestion, decreased appetite, and abdominal cramps were reported in > 1% and < 3% of ibuprofen-treated patients. Xerostomia and gingival ulcer were reported with ibuprofen in < 1% of patients. Duodenitis, glossitis, hematemesis, eructation, hepatorenal syndrome, appetite changes, and rectal bleeding may also occur. Use the lowest effective dose of ibuprofen for the shortest possible duration. Discontinue ibuprofen if a serious GI adverse event is suspected. 
Rare cases of esophagitis have been reported in patients receiving ibuprofen tablets. Ibuprofen-induced esophagitis is characterized by sudden onset odynophagia, pyrosis (heartburn), retrosternal pain, and dysphagia. Severe complications such as esophageal ulceration, esophageal stricture, bleeding, and perforation have been reported rarely. Risk factors for ibuprofen-induced esophageal effects include taking the medication without water and at night. Symptoms usually resolve within days to weeks after stopping the medication.
Pancreatitis has been reported in < 1% of patients receiving oral ibuprofen. 
Amblyopia, xerophthalmia, and altered vision (blurred vision, visual impairment, scotomata, and changes in color vision) have been reported with a probable causal relationship in < 1% of patients receiving oral ibuprofen. If a patient develops visual changes, ibuprofen should be discontinued and an ophthalmologic examination with central visual fields and color vision testing should be performed. Vision generally improves when the drug is discontinued. The mechanism for visual disturbances is unclear. Conjunctivitis, diplopia, optic neuritis and cataracts have been reported in < 1% of patients taking ibuprofen; however, a causal relationship is unknown. Tinnitus has been reported in 1—10% and hearing loss in < 1% of ibuprofen-treated patients.  A prospective analysis examining the association between analgesic use and the risk of hearing loss was conducted in 62,261 women 31—48 years of age at study enrollment who were originally enrolled in the Nurses' Health Study II. Self-reported hearing loss and analgesic use (including acetaminophen, aspirin, and NSAIDs) were examined over 14 years. During 764,247 person-years of follow-up, 10,012 cases of hearing loss were reported. After adjustment for confounders, ibuprofen use >= 2 days per week was independently associated with an increased risk of hearing loss, with the relative risk of hearing loss increasing with increasing frequency of use. Ibuprofen use 2—3, 4—5, or >= 6 days per week was associated with relative risks of 1.13 (95% CI 1.06—1.19), 1.21 (95% CI 1.11—1.32), and 1.24 (95% CI 1.14—1.35), respectively, with a p trend of < 0.0001. Of note, those with more frequent use of ibuprofen were older, had higher body mass indices, were more likely to be past or current smokers, have hypertension, or have diabetes. In a similar study of male patients, the association between professionally diagnosed hearing loss and analgesic use (including acetaminophen, aspirin, and NSAIDs) was prospectively analyzed in 26,917 patients 40—74 years at study enrollment over 18 years. During 369,079 person-years of follow-up, 3488 cases of hearing loss were reported. After adjustment for confounders, the hazard ratio (HR) for NSAID (e.g., ibuprofen) associated hearing loss was 1.21 (95% CI 1.11—1.33, p = 0.1) in patients who were regular users of the drug (>= 2 times weekly) compared to those with less use. Men who regularly used NSAIDs for >= 4 years were 33% (18—49%) more likely to develop hearing loss than those with shorter use. Regular users < 50 years of age were 61% more likely to develop hearing loss compared to non-regular users; regular users 50—59 years had a 32% higher risk of hearing loss, and regular users >= 60 years had a 16% higher risk. These studies do suggest association; however, data are based on patient reporting of the outcomes. Information regarding noise exposure and analgesic doses was not provided.  Ibuprofen or NSAID related ototoxicity may result from several mechanisms, including reduced cochlear blood flow, impairment of outer hair cell function, or inhibition of prostaglandin forming cyclooxygenase. As a true long-term association may exist, counsel patients to minimize long-term treatment with ibuprofen as much as possible.
Ibuprofen has been associated with acute renal failure (unspecified) in patients with pre-existing significantly impaired renal function, decreased creatinine clearance, polyuria, azotemia, cystitis, and hematuria in less than 1% of patients. Abnormal renal function is among the most frequently reported adverse events with ibuprofen or other NSAIDs, occurring in approximately 1% to 10% of patients. It is well known that vasodilatory renal prostaglandins and the potent vasoconstrictor angiotensin II work in concert to maintain renal blood flow. Inhibition of renal prostaglandins by NSAIDs can cause renal insufficiency. This problem can manifest as hyperkalemia, hyperuricemia, or azotemia. Hyperkalemia and other increases in serum potassium concentrations have been reported in patients without renal impairment taking NSAIDs, likely due to a hyporeninemic-hypoaldosteronism state. Renal papillary necrosis has been reported in less than 1% of ibuprofen-treated patients, and has been associated with long-term administration of NSAIDs. With some NSAIDS, nephrotic syndrome, proteinuria, and interstitial nephritis have been reported. Dysuria, oliguria, glomerulonephritis, and renal tubular necrosis have also been reported with the use of ibuprofen. Inhibition of prostaglandin synthesis by NSAIDs potentiates water reabsorption. Fluid retention and edema (peripheral edema) have been reported in 1% to 10% of patients receiving ibuprofen.  Urinary retention (3% to 5%) and increased blood urea (10%) have been reported during adult IV ibuprofen clinical trials. Hyponatremia due to water intoxication has been reported with NSAID use.   Monitoring of the patient's fluid status and serum creatinine and blood urea nitrogen concentrations is recommended.
Like all NSAIDs, ibuprofen-induced increases in water retention and decreases in renal perfusion may exacerbate pre-existing cardiovascular complications, including hypertension (less than 1%) and congestive heart failure (specifically in patients with marginal cardiac function, less than 1%).  Further, NSAIDs may increase the risk of serious cardiovascular thromboembolism, myocardial infarction, and stroke, which can be fatal. Estimates of increased relative risk range from 10% to 50% or more, based on the drug and dose studied. The risk may increase with increased exposure, as measured in dose or duration. Significant cardiovascular risk has been observed within days to weeks of NSAID initiation. The relative increase in cardiovascular thrombotic events over baseline appears to be similar in patients with or without cardiovascular disease or risk factors for cardiovascular disease; however, patients with known cardiovascular disease or risk factors may be at greater risk because of a higher baseline risk of events. While comprehensive data regarding relative cardiovascular safety of any particular NSAID compared to other NSAIDs is not available, celecoxib 100 mg twice daily was shown to be non-inferior to ibuprofen 600 to 800 mg 3 times daily or naproxen 375 to 500 mg twice daily for the composite endpoint of cardiovascular death, nonfatal MI, and nonfatal stroke in osteoarthritis or rheumatoid arthritis adult patients with or at high risk for cardiovascular disease. The intention-to-treat (ITT) analysis followed patients for 30 months, with 8,072 patients randomized to celecoxib, 8,040 randomized to ibuprofen, and 7,969 randomized to naproxen. ITT hazard ratios (95% CI) were 0.93 (0.76 to 1.13) for celecoxib vs. naproxen, 0.86 (0.7 to 1.04) for celecoxib vs. ibuprofen, and 1.08 (0.89 to 1.31) for ibuprofen vs. naproxen. Average 24-hour systolic pressure decreased by 0.3 mmHg in patients receiving celecoxib in a 4-month substudy of 444 patients, while average 24-hour systolic pressures increased by 3.7 mmHg and 1.6 mmHg in patients taking ibuprofen and naproxen, respectively. There is no consistent evidence that concomitant use of aspirin mitigates the increased risk for cardiovascular thrombotic events. In observational studies, data demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality; the incidence of death in the first year post-MI in NSAID-treated patients was 20 per 100 person years compared to 12 per 100 person years in non-NSAID exposed patients. An increased relative risk of death in NSAID users was observed across 4 years of follow-up. A meta-analysis of randomized, controlled trials demonstrated an approximate 2-fold increase in hospitalizations for heart failure among nonselective- and COX-2 selective NSAID-treated patients compared to placebo. Other cardiovascular events reported in ibuprofen-treated patients include: palpitations (less than 1%; probable causal relationship), arrhythmia exacerbation (less than 1%), sinus tachycardia (less than 1%), sinus bradycardia (less than 1%), syncope, hypotension, and vasculitis. Some patients have experienced chest pain (unspecified) during postmarketing use of ibuprofen. Inform patients of the signs and symptoms of CV events, and advise them to seek medical help immediately if such signs or symptoms occur.  
Borderline elevated hepatic enzymes have been reported in up to 15% of patients receiving NSAID therapy; elevated hepatic enzymes have been reported in <= 10% of ibuprofen-treated patients. These abnormalities may persist, progress, or be transient. One percent of patients in clinical trials with NSAIDs had elevations of ALT or AST greater than or equal to 3 times normal values. Rarely, NSAIDs have been associated with hepatotoxicity including jaundice (< 1%), hepatitis (< 1%), hepatic necrosis, and hepatic failure. Ongoing monitoring is recommended in patients who develop signs or symptoms of liver dysfunction and/or with abnormal LFTs. Discontinue ibuprofen in patients with evidence of new onset liver disease.
Ibuprofen has been shown to cause platelet dysfunction; however, this effect is transient and reversible. Prolonged bleeding time is among the most frequently reported adverse events that occur with ibuprofen or other NSAIDs (1% to 10%). The incidence of neutropenia is less than 1% for oral therapy and 7% to 13% for parenteral therapy. Anemia has been reported in 1% to 10% of patients treated with oral ibuprofen or other NSAIDs, and in 17% to 20% of adult patients and more than 2% of pediatric patients treated with parenteral ibuprofen. Other hematologic effects (less than 1%) due to oral ibuprofen include agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, decreases in hemoglobin and hematocrit, and bleeding episodes including epistaxis and menorrhagia. Ecchymosis, leukopenia, purpura, stomatitis, lymphadenopathy, and pancytopenia have been reported with oral ibuprofen. Patients taking parenteral ibuprofen also experienced hypoalbuminemia (3% to 10% ibuprofen vs. 4% placebo) and thrombocythemia/thrombocytosis (3% to 10%).  
Pruritus has been reported in 1—10% of patients taking oral ibuprofen or other NSAIDs and was cited as the most common cause of drug discontinuation in parenteral ibuprofen clinical trials (< 1%). Rash (unspecified), including maculopapular rash, has been reported in 1—10% of patients taking oral ibuprofen. Of patients taking oral ibuprofen, other dermatologic reactions occur less frequently (< 1%), including bullous rash, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, photosensitivity reactions, vesiculobullous eruptions, toxic epidermal necrolysis, and diaphoresis (no incidence reported). Exfoliative dermatitis, a serious and potentially fatal skin reaction, has been reported with other NSAIDs and may occur with ibuprofen. Patients should be instructed to discontinue the medication and contact their health care provider if erythema, rash, blisters, or related skin reactions develop. 
Ibuprofen may cause bronchospasm, dyspnea, and wheezing in patients with asthma. The proposed mechanism of nonsteroidal antiinflammatory drug-sensitive asthma is excessive production of cysteinyl leukotrienes. A single exposure could induce lung function deterioration, as the reaction is not thought to be of an allergic hypersensitivity nature. Likewise, subsequent exposures should not result in escalating bronchospasm severity. Other respiratory-related adverse reactions that have been reported rarely include: apnea, respiratory depression, pneumonia, and rhinitis.  Cough (3% or less) and bacterial pneumonia (3% to 10%) were reported with parenteral ibuprofen-treated patients during adult trials for postoperative pain and fever, respectively.
Dizziness, headache, and nervousness have been reported in 1% to 10% of patients taking ibuprofen or other NSAIDs; patients receiving parenteral ibuprofen in clinical trials experienced dizziness and headache.   In pediatric intravenous ibuprofen trials, headache was among the most common adverse events, occurring at an incidence more than 2%. Overuse of drugs for treating acute headaches, including ibuprofen, may lead to medication overuse headache. Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Discontinuation of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Advise patients about the risks of medication overuse (e.g., use of ibuprofen for at least 15 days/month or any combination of therapy for 10 days/month) and encourage them to keep a written record of headache frequency and drug use.  Pediatric guidelines recommend no more than 14 days/month of over-the-counter medication and no more than 9 days/month of any combination of therapy to avoid medication overuse headache.
Aseptic meningitis has been reported in < 1% of patients taking ibuprofen.  Ibuprofen has been the most common NSAID implicated in this adverse reaction; however, cases have been reported with sulindac, naproxen, tolmetin, diclofenac, ketoprofen, rofecoxib, and piroxicam. No cases of aseptic meningitis were reported among patients receiving intravenous ibuprofen in clinical trials. Aseptic meningitis from one NSAID does not preclude use of another NSAID; most patients can be treated with another drug without incident. However, one patient with Sjogren's syndrome experienced aseptic meningitis after receipt of naproxen, ibuprofen, and rofecoxib at different times; aseptic meningitis developed about a week after each drug exposure, and the symptoms abated roughly 2 days following each drug cessation. The occurrence of aseptic meningitis is not related to NSAID chemical class or prostaglandin inhibition. A Type III or IV immunological hypersensitivity reaction is the proposed mechanism of action. Drug-induced aseptic meningitis usually occurs shortly after drug initiation but can occur after years of drug usage. Although NSAID-induced aseptic meningitis is primarily reported in patients with systemic lupus erythematosus (SLE), healthy patients and patients with other disease states such as ankylosing spondylitis, connective tissue disease, osteoarthritis, and rheumatoid arthritis have developed NSAID-induced aseptic meningitis. Symptoms of aseptic meningitis include feeling confused, somnolence, general feeling of illness, severe headache, nausea, nuchal rigidity, and photophobia. As aseptic meningitis is a diagnosis of exclusion, the suspected drug should be discontinued and not restarted unless a rechallenge is desired.
Oral ibuprofen has been associated infrequently (< 1%; without causal relationship) with the development of pseudotumor cerebri (benign intracranial hypertension).
CNS-related adverse reactions with a probable causal relationship reported in < 1% of ibuprofen-treated patients include: depression, insomnia, confusion, emotional lability, and drowsiness. Those reactions reported in < 1% of patients where the causal relationship to ibuprofen has not been established include: paresthesias, hallucinations, and dream abnormalities. Other CNS-related adverse reactions that have been reported occasionally or rarely include anxiety, asthenia, malaise, tremor, vertigo, seizures and coma.
Fever, infection, and sepsis have been reported in patients receiving ibuprofen.
Allergic reactions with a probable causal relationship to ibuprofen that include a syndrome of abdominal pain, fever, chills, nausea, vomiting, anaphylaxis (anaphylactoid reactions), and bronchospasm have been reported in less than 1% of patients. Other allergic reactions without an established causal relationship to ibuprofen reported in less than 1% of patients include serum sickness, lupus erythematosus syndrome (lupus-like symptoms), Henoch-Schonlein vasculitis, and angioedema. 
Decreased appetite (anorexia) has been reported in 1% to 3% of patients taking ibuprofen during clinical trials. Gynecomastia, hypoglycemia, and metabolic acidosis have been reported with ibuprofen in less than 1% of patients, although a causal relationship has not been established. Weight changes (weight gain, weight loss) and hyperglycemia have also been reported.  Metabolic abnormalities including hypokalemia (19% or less), hypoproteinemia (10% to 13%), and hypernatremia (7% to 10%) were reported during adult clinical trials for parenteral ibuprofen.
In pediatric intravenous ibuprofen trials, infusion site pain (injection site reaction) was among the most common adverse events, occurring at an incidence > 2%.
NSAIDs, such as ibuprofen, may delay or prevent prostaglandin-mediated rupture of ovarian follicles, which has been associated with reversible infertility. Small studies of women treated with NSAIDs demonstrated a reversible delay in ovulation. Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing infertility evaluation.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a multi-organ hypersensitivity reaction, has occurred with NSAIDs. Some of these events have been life-threatening or fatal. DRESS typically presents as fever, rash, and/or lymphadenopathy in conjunction with other organ system involvement including hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Early manifestations such as fever and lymphadenopathy may be present without evidence of a rash. Discontinue the NSAID in patients presenting with such signs and symptoms in whom an alternative etiology cannot be identified.
Ibuprofen is contraindicated in patients with salicylate hypersensitivity or NSAID hypersensitivity who have experienced asthma, urticaria, or other allergic reactions (e.g., anaphylactic reactions and serious skin reactions) after taking ibuprofen, aspirin, or other NSAIDs. Severe, rarely fatal, anaphylactoid reactions to ibuprofen have been reported. Ibuprofen should not be used in patients with aspirin-sensitive asthma or the aspirin triad because of the approximate 5% cross-sensitivity that occurs between aspirin and NSAIDs. The triad typically occurs in patients with asthma who experience rhinitis with or without nasal polyps, or who experience severe, potentially fatal acute bronchospasm after taking aspirin or other NSAIDs. The use of NSAIDs, including ibuprofen, may cause serious and potentially fatal skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Patients should be instructed to discontinue the medication and contact their health care provider if erythema, rash, blisters, or related skin reactions develop. Cautious use of ibuprofen is recommended in patients with asthma. Of 100 children 6 to 18 years of age with mild or moderate persistent asthma, 2% experienced a drop in forced expiratory volume in 1 second (FEV1) of more than 20% and 4% experienced a FEV1 decrease of greater than 15% within 1 hour of ibuprofen ingestion. None of these children had exposure to ibuprofen prior to the study, and none experienced a decline in lung function after placebo.
Chronic use of ibuprofen can result in gastritis, ulceration with or without GI perforation, and/or GI bleeding, which can occur at any time, often without preceding symptoms. Serious and fatal GI adverse reactions including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine have been reported in patients receiving NSAIDs. Therefore, use ibuprofen with caution, if at all, in patients with a history of or active GI disease, including peptic ulcer disease or GI bleeding. Use with caution in patients with other factors known to increase GI bleeding risk including: concomitant oral corticosteroid therapy, anticoagulant therapy, antiplatelet drug use (including low-dose aspirin), chemotherapy, longer duration of NSAID therapy, tobacco smoking, alcoholism or use of alcohol, older age, poor general health status, ulcerative colitis, or Crohn's disease. Most spontaneous reports of fatal GI reactions are in elderly or debilitated patients; special care should be taken in treating this population. Consider alternative (non-NSAID) therapy in at-risk patients. Use this medication for the shortest effective duration and inform patients to promptly report signs and symptoms of GI ulcer or bleeding. Use the lowest effective dosage for the shortest possible duration, and avoid use of more than 1 NSAID at a time. If a serious GI adverse event is suspected, promptly begin evaluation and treatment; discontinue ibuprofen until a serious GI event is ruled out. In the setting of low-dose aspirin for cardiac prophylaxis, monitor patients closely for GI bleeding.
Use ibuprofen with caution in patients with hepatic disease. Severe hepatic reactions have occurred during treatment with ibuprofen, and patients with hepatic impairment are at an increased risk for developing these complications. Ibuprofen elimination may be prolonged in patients with hepatic impairment. Discontinue ibuprofen if elevated hepatic enzymes persist or worsen, or if signs or symptoms of hepatic disease, such as jaundice, develop. In addition, patients with advanced liver disease are at increased risk for GI bleeding.
Ibuprofen is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of thromboembolism, including myocardial infarction and stroke, was found through analysis of data regarding the use of a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) for the treatment of pain in the first 10 to 14 days after CABG surgery. Ibuprofen, like all NSAIDs, may exacerbate heart failure and hypertension and may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Avoid the use of ibuprofen in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If ibuprofen is used in patients with severe heart failure, monitor for signs of worsening heart failure. Trials demonstrated an approximately doubling of hospitalizations for heart failure in patients treated with selective and nonselective NSAIDs compared to placebo-treated patients. Additionally, fluid retention and edema have been observed with NSAID use. Caution is recommended when administering ibuprofen to patients with cardiac disease, cardiomyopathy, cardiac arrhythmias (e.g., tachycardia), significant coronary artery disease (including acute myocardial infarction, angina, or history of myocardial infarction), peripheral vascular disease, cerebrovascular disease (e.g., stroke, transient ischemic attack), hypertension, pre-existing renal disease, or fluid retention. Closely monitor blood pressure during ibuprofen receipt. Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse cardiovascular event. Inform patients to seek immediate medical attention if they experience any signs or symptoms of a cardiovascular thrombotic event. Myocardial infarction or stroke can occur as early as the first weeks of using a NSAID, and risk may increase with higher doses and longer duration of use. NSAIDs may increase the risk of a cardiovascular thrombotic event in patients with or without underlying heart disease or risk factors for heart disease. Patients with known heart disease or risk factors appear to have a greater likelihood of an event after NSAID use, likely due to a higher baseline risk. While comprehensive data regarding relative cardiovascular safety of any particular NSAID compared to other NSAIDs is not available, celecoxib 100 mg twice daily was shown to be non-inferior to ibuprofen 600 to 800 mg 3 times daily or naproxen 375 to 500 mg twice daily for the composite endpoint of cardiovascular death, nonfatal MI, and nonfatal stroke in osteoarthritis or rheumatoid arthritis adult patients with or at high risk for cardiovascular disease. Celecoxib had negligible effect on average 24-hour systolic blood pressure, while average 24-hour systolic pressures increased by 3.7 mmHg and 1.6 mmHg in patients taking ibuprofen and naproxen, respectively. There is no consistent evidence that concomitant use of aspirin mitigates the increased risk for cardiovascular thrombotic events. Guidelines state NSAIDs should not be administered to patients presenting with and hospitalized for ST-elevation myocardial infarction (STEMI) due to increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use. Observational data from a national registry demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, cardiovascular-related death, and all-cause mortality beginning the first week of treatment. An increased relative risk of death in NSAID users continued during the follow-up period of 4 years. Data demonstrate that patients treated with NSAIDs were more likely to die in the first year following a myocardial infarction compared to those not treated with NSAIDs.
The renal effects of ibuprofen may hasten the progression of renal dysfunction in patients with pre-existing renal disease. Correct volume status in patients with dehydration or hypovolemia before starting ibuprofen. Monitor renal function in patients with renal impairment, dehydration, or hypovolemia during ibuprofen use. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction include those with impaired renal function, dehydration, hypovolemia, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment status.
Ibuprofen should be used cautiously in patients with preexisting hematological disease (e.g., coagulopathy or hemophilia) or thrombocytopenia due to the effect of the drug on platelet function and vascular response to bleeding. Ibuprofen should also be used with caution in patients undergoing surgery when a high degree of hemostasis is required. NSAIDs should be used with caution in patients with immunosuppression or neutropenia. NSAIDs may mask the signs of infection such as fever or pain in patients with bone marrow suppression. Patients with coagulopathy are also at increased risk for GI bleeding.
If ibuprofen therapy is undertaken in a geriatric patient, use the lowest effective ibuprofen dose for the shortest possible duration; monitor treatment closely. Due to body system frailties, geriatric patients are at an increased risk of NSAID-related adverse events. Chronic use of ibuprofen can result in gastritis, ulceration with or without perforation, and GI bleeding, which can occur at any time, often without preceding symptoms. Patients of advanced age do not tolerate GI ulceration or bleeding well, and most cases of reported fatal GI events occur in this population. Elderly patients are also more prone to complications related to suboptimal renal perfusion and cardiovascular events.  According to the Beers Criteria, NSAIDs are considered potentially inappropriate medications (PIMs) for use in geriatric patients. NSAIDs may cause new or worsening gastric and duodenal ulcers, and there is an increased risk of GI bleeding and peptic ulcer disease in high-risk groups including those above 75 years of age, or those taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet medications. The risk of ulcers, gross bleeding, or perforation is cumulative with continued use. Avoid the chronic use of NSAIDs in high-risk geriatric patients, unless other alternatives are not effective, and the patient can take a gastroprotective agent. Avoid the use of NSAIDs in patients with a history of gastric or duodenal ulcers, unless other alternatives are not effective and the patient can take a gastroprotective agent. The use of a gastroprotective agent, like a proton pump inhibitor or misoprostol, reduces but does not eliminate, GI risks. NSAIDs can also increase blood pressure and induce kidney injury. Avoid use of NSAIDs in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: symptomatic heart failure (fluid retention, symptom exacerbation) or chronic kidney disease Stage 4 or higher (CrCl less than 30 mL/minute) (acute kidney injury, further decline of renal function). Use with caution in patients with asymptomatic heart failure. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, NSAIDs should be reserved for symptoms and inflammatory conditions for which lower risk analgesics (e.g., acetaminophen) have either failed or are not clinically indicated. NSAIDs may cause GI bleeding in patients with a prior history of, or with increased risk for, GI bleeding. Also, NSAIDs may cause or worsen renal failure, increase blood pressure, or exacerbate heart failure. Some NSAIDs, such as ibuprofen, may reduce the cardioprotective effect of aspirin.
Avoid ibuprofen use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate. If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice. Use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. Observational data regarding embryofetal risks of NSAID use during the first trimester is inconclusive. There are no adequate and well-controlled studies of ibuprofen in pregnant women.
NSAIDs, such as ibuprofen, may pose a reproductive risk by delaying or preventing prostaglandin-mediated rupture of ovarian follicles, which has been associated with reversible infertility. Small studies of women treated with NSAIDs demonstrated a reversible delay in ovulation. Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing infertility evaluation.
Because exposure to a nursing infant is low, especially after single or intermittent doses, ibuprofen is considered a preferred analgesic/anti-inflammatory for women who are breast-feeding. After oral administration, ibuprofen is present in breast milk at relative infant doses of 0.06% to 0.6% of the maternal weight-adjusted daily dose. There are no reports of adverse effects on milk production or on the breast-fed infant. In a study of milk samples from 13 women who took an ibuprofen regimen of approximately 1 g daily, the relative infant dose was less than 0.38% of the mean maternal weight-adjusted dose. The relative infant dose was highest when the milk protein content was highest during the colostral phase.
Patients with systemic lupus erythematosus (SLE) and related connective tissue diseases may be at increased risk of developing aseptic meningitis with fever and coma during ibuprofen therapy. This condition has been observed on rare occasions in patients on ibuprofen and has been reported in patients who do not have an underlying chronic disease. If signs or symptoms of meningitis develop, consider the possibility that it is related to ibuprofen use.
Ibuprofen competitively inhibits both COX-1 and COX-2 by blocking arachidonate binding resulting in analgesic, antipyretic, and anti-inflammatory pharmacologic effects. The enzymes COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin G2 (PGG2), the first step of the synthesis prostaglandins and thromboxanes that are involved in rapid physiological responses. Ibuprofen is effective in cases where inflammation has caused sensitivity of pain receptors (hyperalgesia). It appears prostaglandins, specifically prostaglandins E and F, are responsible for sensitizing the pain receptors; therefore, ibuprofen has an indirect analgesic effect by inhibiting the production of further prostaglandins and does not directly affect hyperalgesia or the pain threshold. Ibuprofen promotes a return to a normal body temperature set point in the hypothalamus by suppressing the synthesis of prostaglandins, specifically PGE2, in circumventricular organs in and near the hypothalamus. Ibuprofen may mask fever in some patients, especially with high or chronic dosing. It appears that the anti-inflammatory effects may be primarily due to inhibition of the COX-2 isoenzyme. However, COX-1 is expressed at some sites of inflammation. COX-1 is expressed in the joints of rheumatoid arthritis or osteoarthritis patients, especially the synovial lining, and it is the primary enzyme of prostaglandin synthesis in human bursitis. Ibuprofen is slightly more selective for COX-1 than COX-2.
Ibuprofen is administered orally and intravenously. The Vd of ibuprofen is dependent on patient age and body temperature; febrile children younger than 11 years have a Vd of approximately 0.2 L/kg while adults have a Vd of approximately 0.12 L/kg. Ibuprofen is highly protein-bound (more than 99% at 20 mcg/mL); at serum concentrations more than 20 mcg/mL, protein binding is saturated and becomes nonlinear. Ibuprofen is a racemic mixture. The S-isomer is responsible for clinical activity. The R-isomer is thought to be pharmacologically inactive; however, approximately 60% of R-ibuprofen is slowly converted to S-ibuprofen in adults. The conversion of R-ibuprofen to S-ibuprofen is lower in children compared with adults. S-ibuprofen is metabolized via hepatic oxidation by CYP2C9 to inactive metabolites. Plasma half-life of ibuprofen is approximately 1.7 to 2.5 hours. Ibuprofen is eliminated in the urine and excretion is nearly complete within 24 hours after the last dose. After ingestion, 45% to 79% of the dose is excreted as metabolites, while approximately 1% and 14% are excreted as free and conjugated ibuprofen, respectively. Some biliary excretion may occur.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9
S-ibuprofen is metabolized via hepatic oxidation by CYP2C9 to inactive metabolites. CYP2C9 is polymorphic; CYP2C9(1) is the wild-type, and CYP2C9(2) and CYP2C9(3) are the most common variants. The variant CYP2C9(3) allele decreases enzyme activity to a greater extent than does CYP2C9(2), but clearance of racemic ibuprofen was reduced among all variant genotypes as compared with the wild-type (1/1). Higher S-ibuprofen concentrations led to greater inhibition of COX-1 (reduced thromboxane B2 concentrations) and greater inhibition of COX-2 (reduced prostaglandin E2 concentrations). Importantly, both thromboxane B2 and prostaglandin E2 concentrations were reduced the most among patients with the CYP2C9 genotypes (3/3), (1/3), (2/3), and (2/2).
Ibuprofen is rapidly absorbed. Peak concentrations are generally reached 1 to 2 hours after administration. Ibuprofen absorption is faster when ibuprofen is given under fasting conditions. Administration with food affects the rate, but not the extent of absorption. When given with food, the Tmax is delayed by approximately 30 to 60 minutes, and Cmax is decreased by approximately 30% to 50%. Time to peak antipyretic effect is 3 to 4 hours and duration of effect is 6 to 8 hours.
Ibuprofen AUC, Cmax, and half-life means (CV%) were 109.3 (26.4) mcg x hour/mL, 39.2 (15.5) mcg/mL, and 2.22 (20.1) hours, respectively, after 400 mg IV over 60 minutes in adults and 192.8 (18.5) mcg x hour/mL, 72.6 (13.2) mcg/mL, and 2.44 (12.9) hours, respectively, after 800 mg IV over 60 minutes in adults. Ibuprofen AUC, Cmax, and half-life means (CV%) were 80.7 (36.9) mcg x hour/mL, 61.9 (26.6) mcg/mL, and 1.55 (26.4) hours, respectively, in children 6 to 16 years, 79.2 (37) mcg x hour/mL, 64.2 (34.3) mcg/mL, and 1.5 (41.8) hours, respectively, in children 2 to 5 years, and 71.1 (37.1) mcg x hour/mL, 59.2 (34.8) mcg/mL, and 1.8 (29.9) hours, respectively, in children 6 months to 1 year after 10 mg/kg IV.
Data have shown that mild hepatic disease does not affect the pharmacokinetics of ibuprofen. However, in adults with moderate to severe hepatic impairment, the elimination half-life of ibuprofen has been shown to be significantly prolonged.
Data have shown that mild or moderate renal impairment does not affect the pharmacokinetics of ibuprofen. Ibuprofen is not recommended in patients with advanced renal disease.
The Vd of ibuprofen (either oral or parenterally administered) is dependent on patient age and body temperature. With single oral doses up to 10 mg/kg, a dose response relationship exists in febrile children. There is also a correlation between the reduction of fever and drug concentration over time. In children, the antipyretic effect of oral therapy begins within 1 hour and peaks within 2 to 4 hours. The analgesic effect is similarly acute in nature. The pharmacokinetic parameters of IV ibuprofen were determined in a study of 42 febrile pediatric patients. Median Tmax occurred at the end of infusion and elimination half-life was shorter in pediatric patients compared to adults (1.5 to 1.8 hours vs. 2.2 to 2.4 hours).
Children and Adolescents 6 to 16 years
Mean pharmacokinetic parameters of ibuprofen 10 mg/kg IV in 25 febrile patients 6 to 16 years of age were as follows: Vd = 10.3 L (226.8 mL/kg); AUC = 80.7 mcg/mL x hour; Cmax = 61.9 mcg/mL; Tmax = 10 minutes; half-life = 1.55 hours; clearance = 4,878.5 mL/hour (109.2 mL/kg/hour).
Children 2 to 5 years
Mean pharmacokinetic parameters of ibuprofen 10 mg/kg IV in 12 febrile patients 2 to 5 years of age were as follows: Vd = 3.7 L (227.2 mL/kg); AUC = 79.2 mcg/mL x hour; Cmax = 64.2 mcg/mL; Tmax = 12 minutes; half-life = 1.5 hours; clearance = 1,967.3 mL/hour (130.1 mL/kg/hour).
Infants and Children 6 months to less than 2 years
Mean pharmacokinetic parameters of ibuprofen 10 mg/kg IV in 5 febrile patients 6 months to less than 2 years of age were as follows: Vd = 2.8 L (311.2 mL/kg); AUC = 71.1 mcg/mL x hour; Cmax = 59.2 mcg/mL; Tmax = 10 minutes; half-life = 1.8 hours; clearance = 1,172.5 mL/hour (133.7 mL/kg/hour).
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