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 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.

nimize the potential risk for an adverse cv event in nsaid-treated patients, use the lowest effective dose for the shortest duration possible. physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous cv symptoms. patients should be informed about the symptoms of serious cv events and the steps to take if they occur. there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cv thrombotic events associated with nsaid use. the concurrent use of aspirin and an nsaid, such as ibuprofen, increases the risk of serious gastrointestinal (gi) events (see warnings) . status post coronary bypass graft (cabg) surgery two large, controlled clinical trials of a cox-2 selective nsaid for the treatment of pain in the first 10-14 days following cabg surgery found an increased incidence of myocardial infarction and stroke. nsaids are contraindicated in the setting of cabg (see contraindications ). post-mi patients observational studies conducted in the danish national registry have demonstrated that patients treated with nsaids in the post-mi period were at increased risk of reinfarction, cv-related death, and all-cause mortality beginning in the first week of treatment. in this same cohort, the incidence of death in the first year post mi was 20 per 100 person years in nsaid-treated patients compared to 12 per 100 person years in non-nsaid exposed patients. although the absolute rate of death declined somewhat after the first year post-mi, the increased relative risk of death in nsaid users persisted over at least the next four years to follow-up. avoid the use of ibuprofen in patients with a recent mi unless the benefits are expected to outweigh the risk of recurrent cv thrombotic events. if ibuprofen is used in patients with a recent mi, monitor patients for signs of cardiac ischemia. hypertension nsaids including ibu tablets, can lead to onset of new hypertensionor worsening of preexisting hypertension, either of which maycontribute to the increased incidence of cv events. patients takingthiazides or loop diuretics may have impaired response to these therapieswhen taking nsaids. nsaids, including ibu tablets, should beused with caution in patients with hypertension. blood pressure (bp)should be monitored closely during the initiation of nsaid treatmentand throughout the course of therapy. heart failure and edema the coxib and traditional nsaid trialists’ collaboration meta-analysis of randomized controlled trails demonstrated an approximately two-fold increase in hospitalizations for heart failure in cox-2 selective-treated patients and nonselective nsaid-treated patients compared to placebo-treated patients. in a danish national registry study of patients with heart failure, nsaid use increased the risk of mi, hospitalization for heart failure, and death. additionally, fluid retention and edema have been observed in some patients treated with nsaids. use of ibuprofen may blunt the cv effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ace inhibitors, or angiotensin receptor blockers (arbs)] [see drug interactions ]. avoid the use of ibu tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. if ibu tablets is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. gastrointestinal effects - risk of ulceration, bleeding, and perforation nsaids, including ibu tablets, can cause serious gastrointestinal(gi) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. these serious adverse events can occur at any time, with or without warning symptoms, in patients treated with nsaids. only one in five patients, who develop a serious upper gi adverse event on nsaid therapy, is symptomatic. upper gi ulcers, gross bleeding, or perforation caused by nsaids occur in approximately 1% of patientstreated for 3-6 months, and in about 2-4% of patients treated for oneyear. these trends continue with longer duration of use, increasing the likelihood of developing a serious gi event at some time during the course of therapy. however, even short-term therapy is not without risk. nsaids should be prescribed with extreme caution in thosewith a prior history of ulcer disease or gastrointestinal bleeding.patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use nsaids have a greater than 10-fold increased risk for developing a gi bleed compared to patients treatedwith neither of these risk factors. other factors that increase the riskof gi bleeding in patients treated with nsaids include concomitant use of oral corticosteroids or anticoagulants, longer duration of nsaid therapy, smoking, use of alcohol, older age, and poor general health status. most spontaneous reports of fatal gi events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. to minimize the potential risk for an adverse gi event in patients treated with an nsaid, the lowest effective dose should be used for the shortest possible duration. patients and physicians should remain alert for signs and symptoms of giulcerations and bleeding during nsaid therapy and promptly initiate additional evaluation and treatment if a serious gi event is suspected.this should include discontinuation of the nsaid until a serious gi adverse event is ruled out. for high-risk patients, alternate therapies that do not involve nsaids should be considered. renal effects long-term administration of nsaids has resulted in renal papillary necrosis and other renal injury. renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. in these patients, administration of a nsaid may cause a dose dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. patients at greatest riskof this reaction are those with impaired renal function, heart failure,liver dysfunction, those taking diuretics and ace inhibitors, and the elderly. discontinuation of nsaid therapy is usually followed by recovery to the pretreatment state. 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 ibu tablets is not recommended in these patients with advanced renal disease. if ibu tablet therapy must be initiated, close monitoring of the patients renal function is advisable. anaphylactoid reactions as with other nsaids, anaphylactoid reactions may occur inpatients without known prior exposure to ibu tablets. ibu 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 anaphylactoidreaction occurs. skin reactions nsaids, including ibu 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, ibu tablets should beavoided because it may cause premature closure of the ductus arteriosus.

ient 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 ibu tablets than do patients with osteoarthritis. the smallest dose of ibu tablets that yields acceptable controlshould be employed. a linear blood level dose-response relationshipexists with single doses up to 800 mg (see clinical pharmacologyfor 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 ibu 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, ibu tablets should be given in adose of 400 mg every 4 hours as necessary for the relief of pain.

ons 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 3200 mg/day thanat doses of 2400 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. table

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 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.

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).

of gastric ulceration with ibuprofenwhereas frank ulceration was reported in 13 patients in the aspiringroup (statistically significant p<.001). gastroscopic studies at varying doses show an increased tendencytoward gastric irritation at higher doses. however, at comparabledoses, gastric irritation is approximately half that seen with aspirin.studies using 51cr-tagged red cells indicate that fecal blood lossassociated with ibuprofen tablets in doses up to 2400 mg daily didnot exceed the normal range, and was significantly less than thatseen in aspirin-treated patients. in clinical studies in patients with rheumatoid arthritis, ibuprofenhas been shown to be comparable to indomethacin in controlling thesigns and symptoms of disease activity and to be associated with astatistically significant reduction of the milder gastrointestinal (see adverse reactions ) and cns side effects. ibuprofen may be used in combination with gold salts and/or corticosteroids. controlled studies have demonstrated that ibuprofen is a more effective analgesic than propoxyphene for the relief of episiotomy pain, pain following dental extraction procedures, and for the relief ofthe symptoms of primary dysmenorrhea. in patients with primary dysmenorrhea, ibuprofen has been shown to reduce elevated levels of prostaglandin activity in the menstrualfluid and to reduce resting and active intrauterine pressure, as well asthe frequency of uterine contractions. the probable mechanism ofaction is to inhibit prostaglandin synthesis rather than simply to provide analgesia. pharmacodynamics in a healthy volunteer study, ibuprofen 400 mg given once daily, administered 2 hours prior to immediate-release aspirin (81 mg) for 6 days, showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane 82 (tx82) inhibition at 24 hours following the day-6 aspirin dose [53%]. an interaction was still observed, but minimized, when ibuprofen 400 mg given once-daily was administered as early as 8 hours prior to the immediate-release aspirin dose [90.7%]. however, there was no interaction with the antiplatelet activity of aspirin when ibuprofen 400 mg, given once daily, was administered 2 hours after (but not concomitantly, 15 min, or 30 min after) the immediate-release aspirin dose [99.2%]. in another study, where immediate-release aspirin 81 mg was administered once daily with ibuprofen 400 mg given three times daily (1, 7, and 13 hours post-aspirin dose) for 10 consecutive days, the mean % serum thromboxane 82 (tx82) inhibition suggested no interaction with the antiplatelet activity of aspirin [98.3%]. however, there were individual subjects with serum tx82 inhibition below 95%, with the lowest being 90.2%. when a similarly designed study was conducted with enteric-coated aspirin, where healthy subjects were administered enteric-coated aspirin 81 mg once daily for 6 days and ibuprofen 400 mg three times daily (2, 7 and 12 h post-aspirin dose) for 6 days, there was an interaction with the antiplatelet activity at 24 hours following the day-6 aspirin dose [67%]. [see precautions/drug interactions ]. pharmacokinetics the ibuprofen in ibu tablets is rapidly absorbed. peak serum ibuprofen levels are generally attained one to two hours after administration.with single doses up to 800 mg, a linear relationship exists between amount of drug administered and the integrated area underthe serum drug concentration vs time curve. above 800 mg, however,the area under the curve increases less than proportional to increases in dose. there is no evidence of drug accumulation or enzyme induction. the administration of ibuprofen tablets either under fasting conditions or immediately before meals yields quite similar serum ibuprofen concentration-time profiles. when ibuprofen is administered immediately after a meal, there is a reduction in the rate of absorption but no appreciable decrease in the extent of absorption.the bioavailability of the drug is minimally altered by the presence of food. a bioavailability study has shown that there was no interference with the absorption of ibuprofen when given in conjunction with anantacid containing both aluminum hydroxide and magnesium hydroxide. ibuprofen is rapidly metabolized and eliminated in the urine. the excretion of ibuprofen is virtually complete 24 hours after the last dose. the serum half-life is 1.8 to 2.0 hours. studies have shown that following ingestion of the drug, 45% to79% of the dose was recovered in the urine within 24 hours as metabolite a (25%), (+)-2-[ p -(2hydroxymethyl-propyl) phenyl] propionic acid and metabolite b (37%), (+)-2-[ p -(2carboxypropyl)phenyl]propionic acid; the percentages of free and conjugated ibuprofen were approximately 1% and 14%, respectively.

llc shreveport, la 71106 usa revised: april 2019 repackaged by: preferred pharmaceuticals inc.

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. • heart failure and edema: advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see warnings ]. • 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.