FDA label 52f9cb72-8416-4e7d-b092-be8d74454cc0

Cardiovascular Risk • NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (See WARNINGS ). • Ibuprofen tablets are contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see 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 ).

Advanced Renal Disease No information is available from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Therefore, treatment with ibuprofen tablets is not recommended in these patients with advanced renal disease. If ibuprofen tablet therapy must be initiated, close monitoring of the patients renal function is advisable.

Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to ibuprofen tablets. Ibuprofen tablets 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 tablets, 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 tablets should be avoided because it may cause premature closure of the ductus arteriosus.

ADVERSE REACTIONS The most frequent type of adverse reaction occurring with ibuprofen tablets is gastrointestinal. In controlled clinical trials the percentage of patients reporting one or more gastrointestinal complaints ranged from 4% to 16%. In controlled studies when ibuprofen tablets were compared to aspirin and indomethacin in equally effective doses, the overall incidence of gastrointestinal complaints was about half that seen in either the aspirin- or indomethacin-treated patients. Adverse reactions observed during controlled clinical trials at an incidence greater than 1% are listed in the table. Those reactions listed in Column one encompass observations in approximately 3,000 patients. More than 500 of these patients were treated for periods of at least 54 weeks. Still other reactions occurring less frequently than 1 in 100 were reported in controlled clinical trials and from marketing experience. These reactions have been divided into two categories: Column two of the table lists reactions with therapy with ibuprofen tablets where the probability of a causal relationship exists: for the reactions in Column three, a causal relationship with ibuprofen tablets has not been established. Reported side effects were higher at doses of 3200 mg/day than at doses of 2400 mg or less per day in clinical trials of patients with rheumatoid arthritis. The increases in incidence were slight and still within the ranges reported in the table. Incidence Greater than 1% (but less than 3%) Probable Causal Relationship Unknown* Precise Incidence Unknown (but less than 1%) Probable Causal Relationship* Precise Incidence Unknown (but less than 1%) Causal Relationship GASTROINTESTINAL Nausea†, epigastric pain†, heartburn†, diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or Pain, fullness of GI tract (bloating and flatulence) Gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests; pancreatitis CENTRAL NERVOUS SYSTEM Dizziness†, headache, nervousness Depression, insomnia, confusion, emotional lability, somnolence, aseptic meningitis with fever and coma (see PRECAUTIONS ) Paresthesias, hallucinations, dream abnormalities, pseudo-tumor cerebri DERMATOLOGIC Rash† (including maculopapular type), pruritus Vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia Toxic epidermal necrolysis, photoallergic skin reactions SPECIAL SENSES Tinnitus Hearing loss, amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision) (see PRECAUTIONS ) Conjunctivitis, diplopia, optic neuritis, cataracts HEMATOLOGIC Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, decreases in hemoglobin and hematocrit (see PRECAUTIONS ) Bleeding episodes (eg epistaxis, menorrhagia) METABOLIC/ENDOCRINE Decreased appetite Gynecomastia, hypoglycemic reaction, acidosis CARDIOVASCULAR Edema, fluid retention (generally responds promptly to drug discontinuation) (see PRECAUTIONS ) Congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations Arrhythmias (sinus tachycardia, sinus bradycardia) ALLERGIC Syndrome of abdominal pain, fever, chills, nausea and vomiting; anaphylaxis; bronchospasm (see CONTRAINDICATIONS ) Serum sickness, lupuserythematosus syndrome. Henoch-Schonlein vasculitis, angioedema RENAL Acute renal failure (see PRECAUTIONS ), decreased creatinine clearance, polyuria, azotemia, cystitis, Hematuria Renal papillary necrosis MISCELLANEOUS Dry eyes and mouth, gingival ulcer, rhinitis * Reactions are classified under “Probable Causal Relationship (PCR)” if there has been one positive rechallenge or if three or more cases occur which might be causally related. Reactions are classified under “Causal Relationship Unknown” if seven or more events have been reported but the criteria for PCR have not been met. † Reactions occurring in 3% to 9% of patients treated with ibuprofen tablets. (Those reactions occurring in less than 3% of the patients are unmarked).

<table width="100%"> <col width="32%"/> <col width="36%"/> <col width="32%"/> <tbody> <tr> <td styleCode="Rrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Incidence Greater than 1%</content> <content styleCode="bold">(but less than 3%)</content> <content styleCode="bold">Probable Causal Relationship Unknown*</content> </paragraph> </td> <td styleCode="Rrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Precise Incidence Unknown</content> <content styleCode="bold">(but less than 1%)</content> <content styleCode="bold">Probable Causal Relationship*</content> </paragraph> </td> <td styleCode="Rrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Precise Incidence</content> <content styleCode="bold">Unknown (but less than 1%)</content> <content styleCode="bold">Causal Relationship</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">GASTROINTESTINAL</content> Nausea&#x2020;, epigastric pain&#x2020;, heartburn&#x2020;, diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or Pain, fullness of GI tract (bloating and flatulence)</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests; pancreatitis</paragraph> </td> <td valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">CENTRAL NERVOUS SYSTEM</content> Dizziness&#x2020;, headache, nervousness</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Depression, insomnia, confusion, emotional lability, somnolence, aseptic meningitis with fever and coma (see <content styleCode="bold"> <linkHtml href="#s16">PRECAUTIONS</linkHtml> </content>)</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Paresthesias, hallucinations, dream abnormalities, pseudo-tumor cerebri</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">DERMATOLOGIC</content> Rash&#x2020; (including maculopapular type), pruritus</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Toxic epidermal necrolysis, photoallergic skin reactions</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">SPECIAL SENSES</content> Tinnitus </paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Hearing loss, amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision) (see <content styleCode="bold"> <linkHtml href="#s16">PRECAUTIONS</linkHtml> </content>)</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Conjunctivitis, diplopia, optic neuritis, cataracts</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">HEMATOLOGIC</content> </paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, decreases in hemoglobin and hematocrit (see <content styleCode="bold"> <linkHtml href="#s16">PRECAUTIONS</linkHtml> </content>)</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Bleeding episodes (eg epistaxis, menorrhagia)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">METABOLIC/ENDOCRINE</content> Decreased appetite</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"/> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Gynecomastia, hypoglycemic reaction, acidosis</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">CARDIOVASCULAR</content> Edema, fluid retention (generally responds promptly to drug discontinuation) (see <content styleCode="bold"> <linkHtml href="#s16">PRECAUTIONS</linkHtml> </content>)</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Arrhythmias (sinus tachycardia, sinus bradycardia)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">ALLERGIC</content> </paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Syndrome of abdominal pain, fever, chills, nausea and vomiting; anaphylaxis; bronchospasm (see <content styleCode="bold"> <linkHtml href="#s5">CONTRAINDICATIONS</linkHtml> </content>)</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Serum sickness, lupuserythematosus syndrome. Henoch-Schonlein vasculitis, angioedema</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">RENAL</content> </paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Acute renal failure (see <content styleCode="bold"> <linkHtml href="#s16">PRECAUTIONS</linkHtml> </content>), decreased creatinine clearance, polyuria, azotemia, cystitis, Hematuria</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Renal papillary necrosis</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">MISCELLANEOUS</content> </paragraph> </td> <td styleCode="Rrule Lrule " valign="top"> <paragraph> Dry eyes and mouth, gingival ulcer, rhinitis</paragraph> </td> <td styleCode="Rrule Lrule " valign="top"/> </tr> <tr> <td colspan="3" styleCode="Botrule " valign="top"> <paragraph> ^*Reactions are classified under &#x201C;Probable Causal Relationship (PCR)&#x201D; if there has been one positive rechallenge or if three or more cases occur which might be causally related. Reactions are classified under &#x201C;Causal Relationship Unknown&#x201D; if seven or more events have been reported but the criteria for PCR have not been met. </paragraph> <paragraph> ^&#x2020;Reactions occurring in 3% to 9% of patients treated with ibuprofen tablets. (Those reactions occurring in less than 3% of the patients are unmarked). </paragraph> </td> </tr> </tbody> </table>