ADVERSE REACTIONS

The most frequent type of adverse reaction occurring with ibuprofen is gastrointestinal. In controlled clinical trials, the percentage of adult patients reporting one or more gastrointestinal complaints ranged from 4% to 16%.

In controlled studies in adults, when ibuprofen was 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 in adults at an incidence greater than 1% are listed in the chart. Those reactions listed under the heading “Incidence Greater than 1% (but less than 3%) Probable Causal Relationship,” 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: “Incidence less than 1%—Probable Causal Relationships,” lists reactions with ibuprofen therapy for which the probability of a causal relationship exists; this category was completed over time with postmarketing serious adverse reactions. “Incidence less than 1%—Causal Relationship Unknown,” lists reactions with ibuprofen therapy for which a causal relationship has not been established, but are presented as alerting information for physicians.

Incidence of 1% or Greater

Probable Causal Relationship:

Incidence between 3 and 9%=ADR marked with *

Incidence between 1 and <3%=unmarked ADR

Cardiovascular system: Edema, fluid retention (generally responds promptly to drug discontinuation) (see PRECAUTIONS).

Digestive system: Nausea*, epigastric pain*, heartburn*, diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or pain, fullness of GI tract (bloating and flatulence).

Nervous system: Dizziness*, headache, nervousness.

Skin and appendages: Rash* (including maculopapular type), pruritus.

Special senses: Tinnitus.

Incidence Less Than 1%

Probable Causal Relationship:The following adverse reactions were reported in clinical trials at an incidence of less than 1%, or were reported from postmarketing or foreign experience. The probability exists between the drug and these adverse reactions.

Body as a whole: Anaphylaxis and anaphylactoid reactions (see WARNINGS).

Cardiovascular system: Cerebrovascular accident, hypotension, congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations.

Digestive system: Gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal hemorrhage, pancreatitis, melena, gastritis, duodenitis, esophagitis, hematemesis, hepatorenal syndrome, liver necrosis, liver failure, hepatitis, jaundice, abnormal liver tests.

Hematologic system: Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, decrease in hemoglobin and hematocrit (see PRECAUTIONS), pancytopenia.

Nervous system: Depression, insomnia, confusion, emotional lability, somnolence, convulsions, aseptic meningitis with fever and coma (see PRECAUTIONS).

Respiratory: Bronchospasm, dyspnea, apnea.

Skin and appendages: Vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, exfoliative dermatitis, Lyell’s syndrome (toxic epidermal necrolysis), photosensitivity reactions.

Special senses: Hearing loss, amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision) (see PRECAUTIONS – Other Precautions).

Urogenital system: Acute renal failure in patients with pre-existing significantly impaired renal function (see PRECAUTIONS), renal papillary necrosis, tubular necrosis, glomerulitis, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria.

Miscellaneous: Dry eyes and mouth, gingival ulcer, rhinitis.

Incidence Less Than 1%

Causal Relationship Unknown:The following adverse reactions occurred at an  incidence of less than 1% in clinical trials, or were suggested by marketing experience under circumstances where a causal relationship could not be definitely established. They are listed as alerting information for the physician.

Allergic: Serum sickness, lupus erythematosus syndrome, Henoch-Schönlein vasculitis, angioedema.

Cardiovascular system: Arrhythmias (sinus tachycardia, sinus bradycardia).

Hematologic system: Bleeding episodes (e.g., epistaxis, menorrhagia).

Metabolic/endocrine: Gynecomastia, hypoglycemic reaction, acidosis.

Nervous system: Paresthesias, hallucinations, dream abnormalities, pseudotumor cerebri.

Special senses: Conjunctivitis, diplopia, optic neuritis, cataracts.

--------------------------