CLASSESCompounding Kits Miscellaneous Show BOXED WARNINGAlcoholism, anticoagulant therapy, chemotherapy, corticosteroid therapy, Crohn's disease, GI bleeding, GI disease, GI perforation, peptic ulcer disease, tobacco smoking, ulcerative colitis 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. Acute myocardial infarction, angina, cardiac arrhythmias, cardiac disease, cardiomyopathy, cerebrovascular disease, coronary artery bypass graft surgery (CABG), coronary artery disease, heart failure, hypertension, myocardial infarction, myocardial infarction or stroke, peripheral vascular disease, stroke, tachycardia, thromboembolism 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. DESCRIPTIONOral and intravenous non-steroidal anti-inflammatory drug (NSAID) COMMON BRAND NAMESAdvil, Advil Children's, Advil Children's Fever, Advil Infants', Advil Junior Strength, Advil Migraine, Caldolor, Children's Ibuprofen, ElixSure IB, EnovaRX, Genpril, Ibren, IBU, Midol, Midol Cramps and Body Aches, Motrin, Motrin Children's, Motrin IB, Motrin Infants', Motrin Junior Strength, Motrin Migraine Pain, PediaCare Children's Pain Reliever/Fever Reducer IB, PediaCare Infants' Pain Reliever/Fever Reducer IB, Samson-8, Toxicology Saliva Collection HOW SUPPLIEDAdvil Children's/Advil Children's Fever/Advil Infants'/Children's Ibuprofen/ElixSure IB/Ibuprofen/Motrin/Motrin Children's/PediaCare Children's Pain Reliever/Fever Reducer IB Oral Susp: 1.25mL, 5mL, 50mg, 100mg
DOSAGE & INDICATIONSFor the treatment of rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA). Oral dosage (tablets or suspension) Adults 300 mg PO 4 times daily or 400 to 800 mg PO 3 to 4 times daily. Max: 3,200 mg/day. Children and Adolescents 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. For the treatment of osteoarthritis. Oral dosage (tablets or suspension) Adults 300 mg PO 4 times daily or 400 to 800 mg PO 3 to 4 times daily. Max: 3,200 mg/day. For the treatment of dysmenorrhea. Oral dosage (tablets or suspension) Adults 400 mg PO every 4 to 6 hours as needed. Max: 3,200 mg/day. Oral dosage (OTC tablets) Adults 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. Children and Adolescents 12 to 17 years 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. For the treatment of moderate to severe pain as an adjunct to opioids. Intravenous dosage Adults 400 to 800 mg IV every 6 hours as needed. Max: 3,200 mg/day. Children and Adolescents 12 to 17 years 400 mg IV every 4 to 6 hours as
needed. Max: 2,400 mg/day. Infants and Children 6 months to 11 years 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. For the treatment of mild pain to moderate pain, including minor aches and pains associated with arthralgia, dental pain, headache, musculoskeletal pain (including backache), and/or the common cold. For the treatment of minor aches and pains associated with arthralgia, dental pain, headache, musculoskeletal pain (including backache), and/or the common cold. Oral dosage (OTC tablets) Adults 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. Children and Adolescents 12 to 17 years 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. Oral dosage (OTC tablets or suspension) Children 11 years or weighing 72 to 95 pounds 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 pain gets worse or lasts more than 3 days. Children 9 to 10 years or weighing 60 to 71 pounds 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 pain gets worse or lasts more than 3 days. Children 6 to 8 years or weighing 48 to 59 pounds 200 mg PO every 6 to 8 hours as needed. Max: 800 mg/day. Discontinue use if no relief within 24 hours or if pain gets worse or lasts more than 3 days. Children 4 to 5 years or weighing 36 to 47 pounds 150 mg PO every 6 to 8 hours as needed. Max: 600 mg/day. Discontinue use if no relief within 24 hours or if pain gets worse or lasts more than 3 days. Children 2 to 3 years or weighing 24 to 35 pounds 100 mg PO every 6 to 8 hours as needed. Max: 400 mg/day. Discontinue use if no relief within 24 hours or if pain gets worse or lasts more than 3 days. Oral dosage (OTC concentrated drops) Children 12 to 23 months or weighing 18 to 23 pounds 75 mg PO every 6 to 8 hours as needed. Max: 300 mg/day. Discontinue use if no relief within 24 hours or if pain gets worse or lasts more than 3 days. Infants 6 to 11 months or weighing 12 to 17 pounds 50 mg PO every 6 to 8 hours as needed. Max: 200 mg/day. Discontinue use if no relief
within 24 hours or if pain gets worse or lasts more than 3 days. For the treatment of mild to moderate pain. Oral dosage (tablets) Adults 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. Oral dosage (suspension) Infants and Children 6 months to 2 years 10 mg/kg/dose PO every 6 to 8 hours. Max: 40 mg/kg/day. Intravenous dosage Adults 400 to 800 mg IV every 6 hours as needed. Max: 3,200 mg/day. Children and Adolescents 12 to 17 years 400 mg IV every 4 to 6 hours as needed. Max: 2,400 mg/day. Infants and Children 6 months to 11 years 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. For the treatment of fever. Oral dosage (OTC tablets) Adults 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. Children and Adolescents 12 to 17 years 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. Oral dosage (OTC tablets or suspension) Children 11 years or weighing 72 to 95 pounds 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. Children 9 to 10 years or weighing 60 to 71 pounds 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. Children 6 to 8 years or weighing 48 to 59 pounds 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. Children 4 to 5 years or weighing 36 to 47 pounds 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. Children 2 to 3 years or weighing 24 to 35 pounds 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. Oral dosage (OTC concentrated drops) Children 12 to 23 months or weighing 18 to 23 pounds 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. Infants 6 to 11 months or weighing 12 to 17 pounds 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. Oral dosage (suspension) Infants and Children 6 months to 2 years 5 to 10 mg/kg/dose PO every 6 to 8 hours. Max: 40 mg/kg/day. Intravenous dosage Adults 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. Children and Adolescents 12 to 17 years 400 mg IV every 4 to 6 hours as needed. Max: 2,400 mg/day. Infants and Children 6 months to 11 years 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. For the acute treatment of migraine. Oral dosage Adults 200 to 400 mg PO once. Guidelines classify ibuprofen as having established efficacy for the treatment of acute migraine. Children† and Adolescents† 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. For patients with cystic fibrosis† to slow the rate of decline in lung function. Oral dosage Adults 20 to 30 mg/kg/dose (Max: 1,600 mg/dose) PO twice daily adjusted to maintain a peak serum concentration of 50 to 100 mcg/mL. Children and Adolescents 6 to 17 years 20 to 30 mg/kg/dose (Max: 1,600 mg/dose) PO twice daily adjusted to maintain a peak serum concentration of 50 to 100 mcg/mL. Guidelines recommend the chronic use of oral ibuprofen for
CF patients 6 to 17 years who have an FEV1 more than 60% predicted. For the treatment of frostbite†. Oral dosage Adults 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. For the treatment of acute or recurrent pericarditis†. For the treatment of acute pericarditis†. Oral dosage Adults 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. Children and Adolescents 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. For the treatment of recurrent pericarditis†. Oral dosage Adults 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. Children and Adolescents 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. †Indicates off-label use MAXIMUM DOSAGEAdults 3,200 mg/day PO/IV for Rx-only products; 1,200 mg/day PO for non-prescription use. Geriatric 3,200 mg/day PO/IV for Rx-only products; 1,200 mg/day PO for non-prescription use. Adolescents 17 years: 3,200 mg/day PO/IV for Rx-only products; 1,200 mg/day PO for non-prescription use. Children 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. Infants 6 to 11 months: 40 mg/kg/day PO/IV. Neonates Safety and efficacy have not been established. DOSING CONSIDERATIONSHepatic Impairment Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Renal Impairment Avoid use of ibuprofen in patients with advanced renal disease unless the benefits are expected to outweigh the risks of worsening renal function.[35893] If use is necessary, monitor renal function closely.[44120] Guidelines recommend the following: Intermittent hemodialysis Peritoneal dialysis Continuous renal replacement therapy (CRRT) ADMINISTRATIONOral Administration Administer orally with milk or food to minimize GI irritation. Oral Liquid Formulations Shake well prior to use. Administer using an oral calibrated measuring device to ensure accurate dosing. Injectable Administration Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. If visibly
opaque particles, discolorations, or other foreign material are observed, do not use the solution. Intravenous Administration Dilution Intravenous infusion STORAGEGeneric: CONTRAINDICATIONS / PRECAUTIONSAcute bronchospasm, asthma, nasal polyps, NSAID hypersensitivity, salicylate hypersensitivity, urticaria 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. Alcoholism, anticoagulant therapy, chemotherapy, corticosteroid therapy, Crohn's disease, GI bleeding, GI disease, GI perforation, peptic ulcer disease, tobacco smoking, ulcerative colitis 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. Hepatic disease 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. Acute myocardial infarction, angina, cardiac arrhythmias, cardiac disease, cardiomyopathy, cerebrovascular disease, coronary artery bypass graft surgery (CABG), coronary artery disease, heart failure, hypertension, myocardial infarction, myocardial infarction or stroke, peripheral vascular disease, stroke, tachycardia, thromboembolism 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. Dehydration, hypovolemia, renal disease, renal failure, renal impairment 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. Bone marrow suppression, coagulopathy, hematological disease, hemophilia, immunosuppression, neutropenia, surgery, thrombocytopenia 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. Geriatric 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.[63923] 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.[60742] Pregnancy 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. Infertility, reproductive risk 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. Breast-feeding 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. Systemic lupus erythematosus (SLE) 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. ADVERSE REACTIONSSevere GI perforation / Delayed / 0-1.0 Moderate anemia / Delayed / 1.0-20.0 Mild pyrosis (heartburn) / Early / 1.0-10.0 DRUG INTERACTIONSAbciximab: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID)
use. Concomitant use increases the risk of bleeding. PREGNANCY AND LACTATIONPregnancy 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. 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. MECHANISM OF ACTIONIbuprofen 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. PHARMACOKINETICSIbuprofen 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.[44121] 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.[35893] The conversion of R-ibuprofen to S-ibuprofen is lower in children compared with adults.[55079] 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.[35893] [44120] [55079] 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.[44120] Some biliary excretion may occur. Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9 Oral Route 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. Intravenous Route 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. |