FDA label ed3783b7-e0ed-8f0a-e053-2995a90a5edc

Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (see WARNINGS and PRECAUTIONS ). Ibuprofen Oral Suspension is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATIONS and WARNINGS ). Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS ).

WARNINGS CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction(MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as ibuprofen, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ). Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS ). Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of Ibuprofen Oral Suspension in patients with a recent MI unless the benefits are expected to outweigh the risks of recurrent CV thrombotic events. If Ibuprofen Oral Suspension is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Hypertension NSAIDs, including Ibuprofen Oral Suspension, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Ibuprofen Oral Suspension, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Heart Failure and Edema The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of ibuprofen may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see Drug Interactions ). Avoid the use of Ibuprofen Oral Suspension in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Ibuprofen Oral Suspension is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation NSAIDs, including Ibuprofen Oral Suspension, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug 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 are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of Ibuprofen Oral Suspension in patients with advanced renal disease. Therefore, treatment with Ibuprofen Oral Suspension is not recommended in these patients with advanced renal disease. If Ibuprofen Oral Suspension therapy must be initiated, close monitoring of the patient's renal function is advisable. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to Ibuprofen Oral Suspension. Ibuprofen Oral Suspension should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS - Preexisting Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including Ibuprofen Oral Suspension, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Pregnancy In late pregnancy, as with other NSAIDs, ibuprofen should be avoided because it may cause premature closure of the ductus arteriosus.

ADVERSE REACTIONS In patients taking ibuprofen or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are: abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, fluid retention, gastrointestinal experiences (including abdominal pain, bloating, constipation, diarrhea, dyspepsia, epigastric pain, flatulence, heartburn, nausea, vomiting), headaches, increased bleeding time, nervousness, pruritus, rashes (including maculopapular) and tinnitus. Additional adverse experiences reported occasionally include: Body as a whole - fever, infection, sepsis Cardiovascular system - congestive heart failure in patients with marginal cardiac function, hypertension, tachycardia, syncope Digestive system - dry mouth, duodenitis, esophagitis, gastric or duodenal ulcer with bleeding and/or perforation, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice, melena, rectal bleeding Hemic and lymphatic system - ecchymosis, eosinophilia, leukopenia, purpura, stomatitis, thrombocytopenia Metabolic and nutritional - weight changes Nervous system - anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, paresthesia, somnolence, tremors, vertigo Respiratory system - asthma, dyspnea Skin and appendages - alopecia, photosensitivity, sweat Special senses - blurred vision Urogenital system - cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, acute renal failure in patients with pre-existing significantly impaired renal function Other adverse reactions, which occur rarely are: Body as a whole - anaphylactic reactions, anaphylactoid reactions, appetite changes Cardiovascular system - arrhythmia, cerebrovascular accident, hypotension, myocardial infarction, palpitations, vasculitis Digestive system - eructation, gingival ulcer, hepatorenal syndrome, liver necrosis, liver failure, pancreatitis Hemic and lymphatic system - agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, neutropenia, pancytopenia Metabolic and nutritional - hyperglycemia Nervous system - convulsions, coma, emotional lability, hallucinations, aseptic meningitis Respiratory - apnea, respiratory depression, pneumonia, rhinitis Skin and appendages - angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, Stevens Johnson syndrome, urticaria, vesiculobullous eruptions Special senses - amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision), conjunctivitis, dry eyes, hearing impairment Urogenital - azotemia, decreased creatinine clearance, glomerulitis, renal papillary necrosis, tubular necrosis

<table width="75%" styleCode="Noautorules"><col align="left" valign="top" width="30%"/><col align="left" valign="top" width="70%"/><tbody><tr><td>Body as a whole -</td><td>fever, infection, sepsis</td></tr><tr><td>Cardiovascular system -</td><td>congestive heart failure in patients with marginal cardiac function, hypertension, tachycardia, syncope</td></tr><tr><td>Digestive system -</td><td>dry mouth, duodenitis, esophagitis, gastric or duodenal ulcer with bleeding and/or perforation, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice, melena, rectal bleeding</td></tr><tr><td>Hemic and lymphatic system -</td><td>ecchymosis, eosinophilia, leukopenia, purpura, stomatitis, thrombocytopenia</td></tr><tr><td>Metabolic and nutritional -</td><td>weight changes</td></tr><tr><td>Nervous system -</td><td>anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, paresthesia, somnolence, tremors, vertigo</td></tr><tr><td>Respiratory system -</td><td>asthma, dyspnea</td></tr><tr><td>Skin and appendages -</td><td>alopecia, photosensitivity, sweat</td></tr><tr><td>Special senses -</td><td>blurred vision</td></tr><tr><td>Urogenital system -</td><td>cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, acute renal failure in patients with pre-existing significantly impaired renal function</td></tr></tbody></table>

<table width="75%" styleCode="Noautorules"><col align="left" valign="top" width="30%"/><col align="left" valign="top" width="70%"/><tbody><tr><td>Body as a whole -</td><td>anaphylactic reactions, anaphylactoid reactions, appetite changes</td></tr><tr><td>Cardiovascular system -</td><td>arrhythmia, cerebrovascular accident, hypotension, myocardial infarction, palpitations, vasculitis</td></tr><tr><td>Digestive system - </td><td>eructation, gingival ulcer, hepatorenal syndrome, liver necrosis, liver failure, pancreatitis</td></tr><tr><td>Hemic and lymphatic system -</td><td>agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, neutropenia, pancytopenia</td></tr><tr><td>Metabolic and nutritional -</td><td>hyperglycemia</td></tr><tr><td>Nervous system -</td><td>convulsions, coma, emotional lability, hallucinations, aseptic meningitis</td></tr><tr><td>Respiratory -</td><td>apnea, respiratory depression, pneumonia, rhinitis</td></tr><tr><td>Skin and appendages -</td><td>angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, Stevens Johnson syndrome, urticaria, vesiculobullous eruptions</td></tr><tr><td>Special senses -</td><td>amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision), conjunctivitis, dry eyes, hearing impairment</td></tr><tr><td>Urogenital -</td><td>azotemia, decreased creatinine clearance, glomerulitis, renal papillary necrosis, tubular necrosis</td></tr></tbody></table>