IBU

INDICATIONS AND USAGE Carefully consider the potential benefits and risks of Ibuprofentablets and other treatment options before deciding to use Ibuprofen.Use the lowest effective dose for the shortest duration consistent withindividual patient treatment goals (see WARNINGS ). Ibuprofen tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ibuprofen tablets are indicated for relief of mild to moderate pain. Ibuprofen tablets are also indicated for the treatment of primary dysmenorrhea. Controlled clinical trials to establish the safety and effectiveness of Ibuprofen tablets in children have not been conducted.

DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of Ibuprofen tabletsand other treatment options before deciding to use Ibuprofen tablets. Usethe lowest effective dose for the shortest duration consistent withindividual patient treatment goals (see WARNINGS ). After observing the response to initial therapy with Ibuprofen tablets, thedose and frequency should be adjusted to suit an individual patient’sneeds.Do not exceed 3200 mg total daily dose. If gastrointestinal complaintsoccur, administer Ibuprofen tablets with meals or milk. Rheumatoid arthritis and osteoarthritis, including flare-ups ofchronic disease: Suggested Dosage: 1,200 mg to 3,200 mg daily (400 mg, 600 mg or 800 mg tid or qid). Individual patients may show a better responseto 3200 mg daily, as compared with 2,400 mg, although in well-controlledclinical trials patients on 3,200 mg did not show a better meanresponse in terms of efficacy. Therefore, when treating patients with 3,200 mg/day, the physician should observe sufficient increased clinicalbenefits to offset potential increased risk.The dose should be tailored to each patient, and may be loweredor raised depending on the severity of symptoms either at time of initiatingdrug therapy or as the patient responds or fails to respond.In general, patients with rheumatoid arthritis seem to require higherdoses of Ibuprofen tablets than do patients with osteoarthritis. The smallest dose of Ibuprofen tablets that yields acceptable controlshould be employed. A linear blood level dose-response relationshipexists with single doses up to 800 mg (See CLINICAL PHARMACOLOGY for effects of food on rate of absorption). The availability of three tablet strengths facilitates dosage adjustment.In chronic conditions, a therapeutic response to therapy with Ibuprofen tablets is sometimes seen in a few days to a week but most often isobserved by two weeks. After a satisfactory response has beenachieved, the patient’s dose should be reviewed and adjusted asrequired. Mild to moderate pain: 400 mg every 4 to 6 hours as necessaryfor relief of pain.In controlled analgesic clinical trials, doses of Ibuprofen tabletsgreater than 400 mg were no more effective than the 400 mg dose. Dysmenorrhea: For the treatment of dysmenorrhea, beginningwith the earliest onset of such pain, Ibuprofen tablets should be given in adose of 400 mg every 4 hours as necessary for the relief of pain.

ADVERSE REACTIONS The most frequent type of adverse reaction occurring withIbuprofen tablets is gastrointestinal. In controlled clinical trials thepercentage of patients reporting one or more gastrointestinal complaintsranged from 4% to 16%. In controlled studies when Ibuprofen tablets were compared toaspirin and indomethacin in equally effective doses, the overall incidenceof gastrointestinal complaints was about half that seen in eitherthe aspirin- or indomethacin-treated patients. Adverse reactions observed during controlled clinical trials at anincidence greater than 1% are listed in the table. Those reactions listedin Column one encompass observations in approximately 3,000patients. More than 500 of these patients were treated for periods ofat least 54 weeks. Still other reactions occurring less frequently than 1 in 100 werereported in controlled clinical trials and from marketing experience.These reactions have been divided into two categories: Column twoof the table lists reactions with therapy with Ibuprofen tablets wherethe probability of a causal relationship exists: for the reactions inColumn three, a causal relationship with Ibuprofen tablets has notbeen established. Reported side effects were higher at doses of 3,200 mg/day thanat doses of 2,400 mg or less per day in clinical trials of patients withrheumatoid arthritis. The increases in incidence were slight and stillwithin the ranges reported in the table. Incidence Greater than 1% (but less than 3%) Probable Causal Relationship* Precise Incidence Unknown (but less than 1%) Probable Causal Relationship** Precise Incidence Unknown (but less than 1%) Causal Relationship Unknown** GASTROINTESTINAL Nausea*, epigastric pain*, heartburn*, diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or Pain, fullness of GI tract (bloating or flatulence). Gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, jaundice, abnormal liver function tests; pancreatitis CENTRAL NERVOUS SYSTEM Dizziness*, headache, nervousness Depression, insomnia, confusion, emotional liability, somnolence, aseptic meningitis with fever and coma (see PRECAUTIONS ) Paresthesias, hallucinations, dream abnormalities, pseudotumor 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, sco-tomata 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, elevate blood pressure, palpitations Arrhythmias (sinus tachycardia, sinus bradycardia) ALLERGIC Syndrome of abdominal pain, fever, chills, nausea and vomiting; anaphylaxis; bronchospasm (see CONTRAINDICATIONS ) Serum sickness, lupus erythematosus syndrome. Henoch- Schonlein vasculitis, angiodema RENAL Acute renal failure (see PRECAUTIONS ), decreased creatinine clearance, poliuria, azotemia, cystitis, Hematuria Renal papillary necrosis MISCELLANEOUS Dry eyes and mouth, gingival ulcer, rhinitis * Reactions occurring in 3% to 9% of patients treated with ibuprofen. (Those reactions occurring in less than 3% of the patients are unmarked.) ** Reactions are classified under “Probable Causal Relationship (PCR)” if there has been one positive rechallange 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. Postmarketing Experience The following adverse reactions have been identified during postapproval use of ibuprofen. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Appendages: Exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Drug Interactions ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensiveeffect of ACE-inhibitors. This interaction should be given considerationin patients taking NSAIDs concomitantly with ACE-inhibitors. Aspirin : Pharmacodynamic studies have demonstrated interference with the antiplatelet activity of aspirin when ibuprofen 400 mg, given three times daily, is administered with enteric­ coated low-dose aspirin. The interaction exists even following a once-daily regimen of ibuprofen 400 mg, particularly when ibuprofen is dosed prior to aspirin. The interaction is alleviated if immediate-release low-dose aspirin is dosed at least 2 hours prior to a once­ daily regimen of ibuprofen; however, this finding cannot be extended to enteric-coated low-dose aspirin [see Clinical Pharmacology/Pharmacodynamics ]. Because there may be an increased risk of cardiovascular events due to the interference of ibuprofen with the antiplatelet effect of aspirin, for patients taking low-dose aspirin for cardio protection who require analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics, where appropriate. When Ibuprofen tablets are administered with aspirin, its protein bindingis reduced, although the clearance of free Ibuprofen tablets is notaltered. The clinical significance of this interaction is not known; however,as with other NSAIDs, concomitant administration of ibuprofenand aspirin is not generally recommended because of the potential forincreased adverse effects.