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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 . 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.

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 . 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 . 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.

Fetal Toxicity Inform pregnant women to avoid use of Ibuprofen and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with Ibuprofen is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours .

Ibuprofen tablets are contraindicated in patients with known hypersensitivityto ibuprofen. Ibuprofen tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin orother NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients . Ibuprofen tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Pregnancy Fetal Toxicity Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs, including Ibuprofen, in pregnant women at about 30 week’s gestation and later. NSAIDs including Ibuprofen, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs, including Ibuprofen, at about 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, for example, 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. If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit Ibuprofen use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if Ibuprofen treatment extends beyond 48 hours.

Discontinue Ibuprofen if oligohydramnios occurs and follow up according to clinical practice Ophthalmological effects . Blurred and/or diminished vision, scotomata, and/or changes incolor vision have been reported. If a patient develops such complaintswhile receiving Ibuprofen tablets, the drug should be discontinued, and thepatient should have an ophthalmologic examination which includescentral visual fields and color vision testing. Pregnancy Risk Summary Use of NSAIDs, including Ibuprofen, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

Because of these risks, limit dose and duration of Ibuprofen use between about 20 and 30 weeks of gestation, and avoid Ibuprofen use at about 30 weeks of gestation and later in pregnancy . Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including Ibuprofen, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data fromobservational studies regarding other potential embryofetal risks of NSAIDuse in women in the first or second trimesters of pregnancy areinconclusive.

Reproductive studies conducted in rats and rabbits have notdemonstrated evidence of developmental abnormalities. However, animalreproduction studies are not always predictive of human response. Basedon animal data, prostaglandins have been shown to have an importantrole in endometrial vascular permeability, blastocyst implantation, anddecidualization.

In animal studies, administration of prostaglandinsynthesis inhibitors such as ibuprofen, resulted in increased pre- and postimplantationloss. Prostaglandins also have been shown to have animportant role in fetal kidney development. In published animal studies,prostaglandin synthesis inhibitors have been reported to impair kidneydevelopment when administered at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus:Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including Ibuprofen, can cause premature closure of the fetal ductus arteriosus . Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If Ibuprofen treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue Ibuprofen and follow up according to clinical practice . Data Human Data There are no adequate, well-controlled studies in pregnant women.

Ibuprofen tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Premature Closure of Fetal Ductus Arteriosus: There are no adequate, well-controlled studies in pregnant women. Ibuprofen tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with 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. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug.

There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications.

These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain. Labor and Delivery In rat studies with NSAIDs, as with other drugs known to inhibitprostaglandin synthesis, an increased incidence of dystocia, delayedparturition, and decreased pup survival occurred.

The effects of Ibuprofen tablets on labor and delivery in pregnant women are unknown. Nursing Mothers It is not known whether this drug is excreted in human milk.Because many drugs are excreted in human-milk and because of thepotential for serious adverse reactions in nursing infants from Ibuprofen tablets, a decision should be made whether to discontinue nursing ordiscontinue the drug, taking into account the importance of the drugto the mother. Pediatric Use Safety and effectiveness of Ibuprofen tablets in pediatric patients havenot been established.

Geriatric Use As with any NSAIDs, caution should be exercised in treating theelderly (65 years and older).

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 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) 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 Bleeding episodes (eg epistaxis, menorrhagia) METABOLIC/ENDOCRINE Decreased appetite Gynecomastia, hypoglycemic reaction, acidosis CARDIOVASCULAR Edema, fluid retention (generally responds promptly to drug discontinuation) 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 Serum sickness, lupus erythematosus syndrome. Henoch- Schonlein vasculitis, angiodema RENAL Acute renal failure , 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).