PRECAUTIONS General IBU tablets cannot be expected to substitute for corticosteroids orto treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroidsmay lead to disease exacerbation. Patients on prolongedcorticosteroid therapy should have their therapy tapered slowly if adecision is made to discontinue corticosteroids. The pharmacological activity of IBU tablets in reducing fever andinflammation may diminish the utility of these diagnostic signs indetecting complications of presumed noninfectious, painful conditions. Hepatic effects Borderline elevations of one or more liver tests may occur in upto 15% of patients taking NSAIDs, including IBU tablets. These laboratoryabnormalities may progress, may remain unchanged, or maybe transient with continuing therapy. Notable elevations of ALT orAST (approximately three or more times the upper limit of normal)have been reported in approximately 1% of patients in clinical trialswith NSAIDs. In addition, rare cases of severe hepatic reactions,including jaundice, fulminant hepatitis, liver necrosis, and hepaticfailure, some of them with fatal outcomes have been reported. Apatient with symptoms and/or signs suggesting liver dysfunction, orwith abnormal liver test values, should be evaluated for evidence ofthe development of a more severe hepatic reaction while on therapywith IBU tablets. If clinical signs and symptoms consistent with liverdisease develop, or if systemic manifestations occur (e.g.,eosinophilia, rash, etc.), IBU tablets should be discontinued. Hematological effects Anemia is sometimes seen in patients receiving NSAIDs, includingIBU tablets. This may be due to fluid retention, occult or gross GIblood loss, or an incompletely described effect upon erythropoiesis.Patients on long-term treatment with NSAIDs, including IBU tablets,should have their hemoglobin or hematocrit checked if they exhibitany signs or symptoms of anemia. In two postmarketing clinical studies the incidence of a decreasedhemoglobin level was greater than previously reported. Decrease inhemoglobin of 1 gram or more was observed in 17.1% of 193patients on 1600 mg ibuprofen daily (osteoarthritis), and in 22.8% of189 patients taking 2400 mg of ibuprofen daily (rheumatoid arthritis).Positive stool occult blood tests and elevated serum creatinine levelswere also observed in these studies. NSAIDs inhibit platelet aggregation and have been shown to prolongbleeding time in some patients. Unlike aspirin, their effect onplatelet function is quantitatively less, of shorter duration, and reversible. Patients receiving IBU tablets who may be adversely affected byalterations in platelet function, such as those with coagulation disordersor patients receiving anticoagulants should be carefully monitored. Preexisting asthma Patients with asthma may have aspirin-sensitive asthma. The useof aspirin in patients with aspirin-sensitive asthma has been associatedwith severe bronchospasm, which can be fatal. Since cross reactivity,including bronchospasm, between aspirin and NSAIDs hasbeen reported in such aspirin-sensitive patients, IBU tablets shouldnot be administered to patients with this form of aspirin sensitivityand should be used with caution in patients with preexisting asthma. Ophthalmological effects Blurred and/or diminished vision, scotomata, and/or changes incolor vision have been reported. If a patient develops such complaintswhile receiving IBU tablets, the drug should be discontinued, and thepatient should have an ophthalmologic examination which includescentral visual fields and color vision testing. Aseptic Meningitis Aseptic meningitis with fever and coma has been observed on rareoccasions in patients on ibuprofen therapy. Although it is probablymore likely to occur in patients with systemic lupus erythematosusand related connective tissue diseases, it has been reported inpatients who do not have an underlying chronic disease. If signs orsymptoms of meningitis develop in a patient on IBU tablets, the possibilityof its being related to IBU tablets should be considered. Information for Patients Patients should be informed of the following information beforeinitiating therapy with an NSAID and periodically during the course ofongoing therapy. Patients should also be encouraged to read theNSAID Medication Guide that accompanies each prescription dispensed • IBU tablets like other NSAIDs, may cause serious CV side effects,such as MI or stroke, which may result in hospitalization and evendeath. Although serious CV events can occur without warningsymptoms, patients should be alert for the signs and symptoms ofchest pain, shortness of breath, weakness, slurring of speech, andshould ask for medical advice when observing any indicative sign orsymptoms. Patients should be apprised of the importance of thisfollow-up (see WARNINGS, Cardiovascular Effects ). • IBU tablets, like other NSAIDs, can cause GI discomfort and, rarely,serious GI side effects, such as ulcers and bleeding, which mayresult in hospitalization and even death. Although serious GI tractulcerations and bleeding can occur without warning symptoms,patients should be alert for the signs and symptoms of ulcerationsand bleeding, and should ask for medical advice when observingany indicative signs or symptoms including epigastric pain, dyspepsia,melena, and hematemesis. Patients should be apprised of theimportance of this follow-up (see WARNINGS, Gastrointestinal Effects-Risk of Ulceration , Bleeding and Perforation) . • IBU tablets, like other NSAIDs, can cause serious skin side effectssuch as exfoliative dermatitis, SJS and TEN, which may result inhospitalization and even death. Although serious skin reactions mayoccur without warning, patients should be alert for the signs andsymptoms of skin rash and blisters, fever, or other signs of hypersensitivitysuch as itching, and should ask for medical advice whenobserving any indicative sign or symptoms. Patients should beadvised to stop the drug immediately if they develop any type ofrash and contact their physicians as soon as possible. • Patients should promptly report signs or symptoms of unexplainedweight gain or edema to their physicians. • Patients should be informed of the warning signs and symptoms ofhepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice,right upper quadrant tenderness and "flu-like" symptoms). If theseoccur, patients should be instructed to stop therapy and seek immediatemedical therapy. • Patients should be informed of the signs of an anaphylactoid reaction(e.g. difficulty breathing, swelling of the face or throat). If theseoccur, patients should be instructed to seek immediate emergencyhelp (see WARNINGS) . • In late pregnancy, as with other NSAIDs, IBU tablets should beavoided because it may cause premature closure of the ductus arteriosus. Laboratory Tests Because serious GI tract ulcerations and bleeding can occur withoutwarning symptoms, physicians should monitor for signs orsymptoms of GI bleeding. Patients on long-term treatment withNSAIDs should have their CBC and chemistry profile checked periodically.If clinical signs and symptoms consistent with liver or renaldisease develop, systemic manifestations occur (e.g., eosinophilia,rash etc.), or abnormal liver tests persist or worsen, IBU tabletsshould be discontinued. 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 When IBU tablets are administered with aspirin, its protein bindingis reduced, although the clearance of free IBU 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. Diuretics Clinical studies, as well as post marketing observations, haveshown that Ibuprofen tablets can reduce the natriuretic effect-offurosemide and thiazides in some patients. This response has beenattributed to inhibition of renal prostaglandin synthesis. During concomitanttherapy with NSAIDs, the patient should be observed closelyfor signs of renal failure (see PRECAUTIONS, Renal Effects), aswell as to assure diuretic efficacy. Lithium Ibuprofen produced an elevation of plasma lithium levels and areduction in renal lithium clearance in a study of eleven normal volunteers.The mean minimum lithium concentration increased 15%and the renal clearance of lithium was decreased by 19% during thisperiod of concomitant drug administration.This effect has been attributed to inhibition of renal prostaglandinsynthesis by ibuprofen. Thus, when ibuprofen and lithium are administeredconcurrently, subjects should be observed carefully for signsof lithium toxicity. (Read circulars for lithium preparation before useof such concurrent therapy.) Methotrexate NSAIDs have been reported to competitively inhibit methotrexateaccumulation in rabbit kidney slices. This may indicate that they couldenhance the toxicity of methotrexate. Caution should be used whenNSAIDs are administered concomitantly with methotrexate. Warfarin-type anticoagulants Several short-term controlled studies failed to show that Ibuprofentablets significantly affected prothrombin times or a variety of otherclotting factors when administered to individuals on coumarin-typeanticoagulants. However, because bleeding has been reported whenIBU tablets and other NSAIDs have been administered to patients oncoumarin-type anticoagulants, the physician should be cautiouswhen administering IBU tablets to patients on anticoagulants. Theeffects of warfarin and NSAIDs on GI bleeding are synergistic, suchthat the users of both drugs together have a risk of serious GI bleedinghigher than users of either drug alone. H-2 Antagonists In studies with human volunteers, co-administration of cimetidineor ranitidine with ibuprofen had no substantive effect on ibuprofenserum concentrations. Pregnancy Teratogenic effects: Pregnancy Category C Reproductive studies conducted in rats and rabbits have notdemonstrated evidence of developmental abnormalities. However,animal reproduction studies are not always predictive of humanresponse. There are no adequate and well-controlled studies in pregnantwomen. Ibuprofen should be used in pregnancy only if thepotential benefit justifies the potential risk to the fetus. Nonteratogenic effects Because of the known effects of NSAIDs on the fetal cardiovascularsystem (closure of ductus arteriosus), use during late pregnancyshould be avoided. 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 IBUtablets 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 IBUtablets, 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 IBU tablets in pediatric patients havenot been established. Geriatric Use As with any NSAIDs, caution should be exercised in treating theelderly (65 years and older).