se aspirin for cardioprotection who require analgesics, consider use of an nsaid that does not interfere with the antiplatelet effect of aspirin, or non-nsaid analgesics, where appropriate. as with other nsaids, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects. diuretics clinical studies, as well as post marketing observations, have shown that ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients. this response has been attributed to inhibition of renal prostaglandin synthesis. during concomitant therapy with nsaids, the patient should be observed closely for signs of renal failure (see warnings, renal effects ), as well as to assure diuretic efficacy. lithium ibuprofen produced an elevation of plasma lithium levels and a reduction 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 this period of concomitant drug administration. this effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (read circulars for lithium preparation before use of such concurrent therapy.) methotrexate nsaids have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. this may indicate that they could enhance the toxicity of methotrexate. caution should be used when nsaids are administered concomitantly with methotrexate. warfarin several short-term controlled studies failed to show that ibuprofen significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on warfarin-type anticoagulants. however, because bleeding has been reported when ibuprofen and other nsaids have been administered to patients on warfarin-type anticoagulants, the physician should be cautious when administering ibuprofen to patients on anticoagulants. the effects of warfarin and nsaids on gi bleeding are synergistic, such that the users of both drugs together have a risk of serious gi bleeding higher than users of either drug alone.

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 signs and/or 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 artery bypass graft (cabg) surgery two large, controlled clinical trials of a cox-2 selective nsaid for the treatment of pain in the first 10 to 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 of follow-up. avoid the use of ibuprofen oral suspension in patients with a recent mi unless the benefits are expected to outweigh the risk of recurrent cv thrombotic events. if ibuprofen oral suspension is used in patients with a recent mi, monitor patients for signs of cardiac ischemia. hypertension nsaids, including ibuprofen, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cv events. patients taking thiazides or loop diuretics may have impaired response to these therapies when taking nsaids. nsaids, including ibuprofen, should be used with caution in patients with hypertension. blood pressure (bp) should be monitored closely during the initiation of nsaid treatment and throughout the course of therapy. heart failure and edema the coxib and traditional nsaid trialists' collaboration meta-analysis of randomized controlled trials demonstrated an approximately 2-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 ibuprofen oral suspension in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. if ibuprofen oral suspension 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 ibuprofen, 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 patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. 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 those with 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 risk for developing a gi bleed compared to patients with neither of these risk factors. other factors that increase the risk for 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 gi ulceration and bleeding during nsaid therapy and promptly initiate additional evaluation and treatment if a serious gi adverse 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 nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. patients at greatest risk of 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 in patients with advanced renal disease. therefore, treatment with ibuprofen is not recommended in these patients with advanced renal disease. if ibuprofen therapy must be initiated, close monitoring of the patient's renal function is advisable. anaphylactoid reactions as with other nsaids, anaphylactoid reactions may occur in patients without known prior exposure to ibuprofen. ibuprofen 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 anaphylactoid reaction occurs. skin reactions nsaids, including ibuprofen, 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. drug reaction with eosinophilia and systemic symptoms (dress) drug reaction with eosinophilia and systemic symptoms (dress) has been reported in patients taking nsaids such as ibuprofen oral suspension. some of these events have been fatal or life-threatening. dress typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. sometimes symptoms of dress may resemble an acute viral infection. eosinophilia is often present. because this disorder is variable in its presentation, other organ systems not noted here may be involved. it is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. if such signs or symptoms are present, discontinue ibuprofen oral suspension and evaluate the patient immediately. fetal toxicity premature closure of fetal ductus arteriosus avoid use of nsaids, including ibuprofen oral suspension, in pregnant women at about 30 weeks gestation and later. nsaids including ibuprofen oral suspension, 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 oral suspension, 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 post marketing 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 oral suspension use to the lowest effective dose and shortest duration possible. consider ultrasound monitoring of amniotic fluid if ibuprofen oral suspension treatment extends beyond 48 hours. discontinue ibuprofen oral suspension if oligohydramnios occurs and follow up according to clinical practice (see precautions; pregnancy ).

hs up to 2 years of age, the recommended dosage is 10 mg/kg, every 6 to 8 hours. the recommended maximum daily dose is 40 mg/kg. doses should be given so as not to disturb the child's sleep pattern. juvenile arthritis the recommended dose is 30 to 40 mg/kg/day divided into three to four doses (see individualization of dosage ). patients with milder disease may be adequately treated with 20 mg/kg/day. in patients with juvenile arthritis, doses above 50 mg/kg/day are not recommended because they have not been studied and doses exceeding the upper recommended dose of 40 mg/kg/day may increase the risk of causing serious adverse events. the therapeutic response may require from a few days to several weeks to be achieved. once a clinical effect is obtained, the dosage should be lowered to the smallest dose of ibuprofen oral suspension needed to maintain adequate control of symptoms. pediatric patients receiving doses above 30 mg/kg/day or if abnormal liver function tests have occurred with previous nsaid treatments should be carefully followed for signs and symptoms of early liver dysfunction. adults primary dysmenorrhea for the treatment of primary dysmenorrhea, beginning with the earliest onset of such pain, ibuprofen oral suspension should be given in a dose of 400 mg every 4 hours, as necessary, for the relief of pain. rheumatoid arthritis and osteoarthritis suggested dosage: 1200 to 3200 mg daily (300 mg q.i.d. or 400 mg, 600 mg or 800 mg t.i.d. or q.i.d.). individual patients may show a better response to 3200 mg daily, as compared with 2400 mg, although in well-controlled clinical trials patients on 3200 mg did not show a better mean response in terms of efficacy. therefore, when treating patients with 3200 mg/day, the physician should observe sufficient increased clinical benefits to offset potential increased risk. individualization of dosage the dose of ibuprofen oral suspension should be tailored to each patient, and may be lowered or raised from the suggested doses depending on the severity of symptoms either at time of initiating drug therapy or as the patient responds or fails to respond. one fever study showed that, after the initial dose of ibuprofen oral suspension, subsequent doses may be lowered and still provide adequate fever control. in a situation when low fever would require the ibuprofen oral suspension 5 mg/kg dose in a child with pain, the dose that will effectively treat the predominant symptom should be chosen. in chronic conditions, a therapeutic response to ibuprofen therapy is sometimes seen in a few days to a week, but most often is observed by two weeks. after a satisfactory response has been achieved, the patient's dose should be reviewed and adjusted as required. patients with rheumatoid arthritis seem to require higher doses than do patients with osteoarthritis. the smallest dose of ibuprofen oral suspension that yields acceptable control should be employed. ibuprofen oral suspension may be used in combination with gold salts and/or corticosteroids.

ystem - ecchymosis, eosinophilia, leukopenia, purpura, stomatitis, thrombocytopenia metabolic and nutritional - weight changes nervous system - anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, paresthesia, somnolence, tremors, vertigo respiratory system - asthma, dyspnea skin and appendages - alopecia, photosensitivity, sweat special senses - blurred vision urogenital system - cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, acute renal failure in patients with pre-existing significantly impaired renal function other adverse reactions, which occur rarely are: body as a whole - anaphylactic reactions, anaphylactoid reactions, appetite changes cardiovascular system - arrhythmia, cerebrovascular accident, hypotension, myocardial infarction, palpitations, vasculitis digestive system - eructation, gingival ulcer, hepatorenal syndrome, liver necrosis, liver failure, pancreatitis hemic and lymphatic system - agranulocystosis, hemolytic anemia, aplastic anemia, lymphadenopathy, neutropenia, pancytopenia metabolic and nutritional - hyperglycemia nervous system - convulsions, coma, emotional lability, hallucinations, aseptic meningitis respiratory - apnea, respiratory depression, pneumonia, rhinitis skin and appendages - angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, stevens johnson syndrome, urticaria, vesiculobullous eruptions special senses - amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision), conjunctivitis, dry eyes, hearing impairment urogenital - azotemia, decreased creatinine clearance, glomerulitis, renal papillary necrosis, tubular necrosis to report suspected adverse events, contact taro pharmaceuticals u.s.a., inc. at 1-866-923-4914 or fda at 1-800-fda-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

se aspirin for cardioprotection who require analgesics, consider use of an nsaid that does not interfere with the antiplatelet effect of aspirin, or non-nsaid analgesics, where appropriate. as with other nsaids, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects. diuretics clinical studies, as well as post marketing observations, have shown that ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients. this response has been attributed to inhibition of renal prostaglandin synthesis. during concomitant therapy with nsaids, the patient should be observed closely for signs of renal failure (see warnings, renal effects ), as well as to assure diuretic efficacy. lithium ibuprofen produced an elevation of plasma lithium levels and a reduction 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 this period of concomitant drug administration. this effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (read circulars for lithium preparation before use of such concurrent therapy.) methotrexate nsaids have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. this may indicate that they could enhance the toxicity of methotrexate. caution should be used when nsaids are administered concomitantly with methotrexate. warfarin several short-term controlled studies failed to show that ibuprofen significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on warfarin-type anticoagulants. however, because bleeding has been reported when ibuprofen and other nsaids have been administered to patients on warfarin-type anticoagulants, the physician should be cautious when administering ibuprofen to patients on anticoagulants. the effects of warfarin and nsaids on gi bleeding are synergistic, such that the users of both drugs together have a risk of serious gi bleeding higher than users of either drug alone.

risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. however, animal reproduction studies are not always predictive of human response. based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as ibuprofen, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development 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 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 oral suspension, can cause premature closure of the fetal ductus arteriosus (see warnings; fetal toxicity ). 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 oral suspension treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue ibuprofen oral suspension and follow up according to clinical practice (see warnings; fetal toxicity ). data human data there are no adequate and well-controlled studies in pregnant women. ibuprofen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. premature closure of fetal ductus arteriosus published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. 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.

s 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 b2 (txb2) inhibition suggested no interaction with the antiplatelet activity of aspirin [98.3%]. however, there were individual subjects with serum txb2 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 ibuprofen is a racemic mixture of [-]r-and [+]s-isomers. in vivo and in vitro studies indicate that the [+]s-isomer is responsible for clinical activity. the [-]r-form, while thought to be pharmacologically inactive, is slowly and incompletely (~ 60%) interconverted into the active [+]s species in adults. the degree of interconversion in children is unknown, but is thought to be similar. the [-]r-isomer serves as a circulating reservoir to maintain levels of active drug. ibuprofen is well absorbed orally, with less than 1% being excreted in the urine unchanged. it has a biphasic elimination time curve with a plasma half-life of approximately 2 hours. studies in febrile children have established the dose-proportionality of 5 and 10 mg/kg doses of ibuprofen. studies in adults have established the dose-proportionality of ibuprofen as a single oral dose from 50 to 600 mg for total drug and up to 1200 mg for free drug. absorption in vivo studies indicate that ibuprofen is well absorbed orally from the suspension formulation, with peak plasma levels usually occurring within 1 to 2 hours (see table 1 ). table 1 pharmacokinetic parameters of ibuprofen oral suspension [mean values (% coefficient of variation)] dose 200 mg (2.8 mg/kg) in adults 10 mg/kg in febrile children formulation suspension suspension legend: auc inf = area-under-the-curve to infinity t max = time-to-peak plasma concentration c max = peak plasma concentration cl/f = clearance divided by fraction at drug absorbed number of patients 24 18 auc inf (mcg∙h/ml) 64 (27%) 155 (24%) c max (mcg/ml) 19 (22%) 55 (23%) t max (h) 0.79 (69%) 0.97 (57%) cl/f (ml/h/kg) 45.6 (22%) 68.6 (22%) antacids a bioavailability study in adults has shown that there was no interference with the absorption of ibuprofen when given in conjunction with an antacid containing both aluminum hydroxide and magnesium hydroxide. h-2 antagonists in studies with human volunteers, coadministration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations. food effects absorption is most rapid when ibuprofen is given under fasting conditions. administration of ibuprofen with food affects the rate but not the extent of absorption. when taken with food, t max is delayed by approximately 30 to 60 minutes, and peak levels are reduced by approximately 30 to 50%. distribution ibuprofen, like most drugs of its class, is highly protein bound (>99% bound at 20 mcg/ml). protein binding is saturable and at concentrations >20 mcg/ml binding is non-linear. based on oral dosing data there is an age- or fever-related change in volume of distribution for ibuprofen. febrile children <11 years old have a volume of approximately 0.2 l/kg while adults have a volume of approximately 0.12 l/kg. the clinical significance of these findings is unknown. metabolism following oral administration, the majority of the dose was recovered in the urine within 24 hours as the hydroxy-(25%) and carboxypropyl-(37%) phenylpropionic acid metabolites. the percentages of free and conjugated ibuprofen found in the urine were approximately 1% and 14%, respectively. the remainder of the drug was found in the stool as both metabolites and unabsorbed drug. elimination ibuprofen is rapidly metabolized and eliminated in the urine. the excretion of ibuprofen is virtually complete 24 hours after the last dose. it has a biphasic plasma elimination time curve with a half-life of approximately 2 hours. there is no difference in the observed terminal elimination rate or half-life between children and adults, however, there is an age- or fever-related change in total clearance. this suggests that the observed change in clearance is due to changes in the volume of distribution of ibuprofen (see table 1 for cl/f values). clinical studies controlled clinical trials comparing doses of 5 and 10 mg/kg ibuprofen suspension and 10 to 15 mg/kg of acetaminophen elixir have been conducted in children 6 months to 12 years of age with fever primarily due to viral illnesses. in these studies there were no differences between treatments in fever reduction for the first hour and maximum fever reduction occurred between 2 and 4 hours. response after 1 hour was dependent on both the level of temperature elevation as well as the treatment. in children with baseline temperatures at or below 102.5°f both ibuprofen doses and acetaminophen were equally effective in their maximum effect. in children with temperatures above 102.5°f, the ibuprofen 10 mg/kg dose was more effective. by 6 hours, children treated with ibuprofen 5 mg/kg tended to have recurrence of fever, whereas children treated with ibuprofen 10 mg/kg still had significant fever reduction at 8 hours. in control groups treated with 10 mg/kg acetaminophen, fever reduction resembled that seen in children treated with 5 mg/kg of ibuprofen, with the exception that temperature elevation tended to return 1 to 2 hours earlier. in patients with primary dysmenorrhea, ibuprofen has been shown to reduce elevated levels of prostaglandin activity in the menstrual fluid and to reduce testing and active intrauterine pressure, as well as the frequency of uterine contractions. the probable mechanism of action is to inhibit prostaglandin synthesis rather than simply to provide analgesia.

ell absorbed orally from the suspension formulation, with peak plasma levels usually occurring within 1 to 2 hours (see table 1 ). table 1 pharmacokinetic parameters of ibuprofen oral suspension [mean values (% coefficient of variation)] dose 200 mg (2.8 mg/kg) in adults 10 mg/kg in febrile children formulation suspension suspension legend: auc inf = area-under-the-curve to infinity t max = time-to-peak plasma concentration c max = peak plasma concentration cl/f = clearance divided by fraction at drug absorbed number of patients 24 18 auc inf (mcg∙h/ml) 64 (27%) 155 (24%) c max (mcg/ml) 19 (22%) 55 (23%) t max (h) 0.79 (69%) 0.97 (57%) cl/f (ml/h/kg) 45.6 (22%) 68.6 (22%) antacids a bioavailability study in adults has shown that there was no interference with the absorption of ibuprofen when given in conjunction with an antacid containing both aluminum hydroxide and magnesium hydroxide. h-2 antagonists in studies with human volunteers, coadministration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations. food effects absorption is most rapid when ibuprofen is given under fasting conditions. administration of ibuprofen with food affects the rate but not the extent of absorption. when taken with food, t max is delayed by approximately 30 to 60 minutes, and peak levels are reduced by approximately 30 to 50%. distribution ibuprofen, like most drugs of its class, is highly protein bound (>99% bound at 20 mcg/ml). protein binding is saturable and at concentrations >20 mcg/ml binding is non-linear. based on oral dosing data there is an age- or fever-related change in volume of distribution for ibuprofen. febrile children <11 years old have a volume of approximately 0.2 l/kg while adults have a volume of approximately 0.12 l/kg. the clinical significance of these findings is unknown. metabolism following oral administration, the majority of the dose was recovered in the urine within 24 hours as the hydroxy-(25%) and carboxypropyl-(37%) phenylpropionic acid metabolites. the percentages of free and conjugated ibuprofen found in the urine were approximately 1% and 14%, respectively. the remainder of the drug was found in the stool as both metabolites and unabsorbed drug. elimination ibuprofen is rapidly metabolized and eliminated in the urine. the excretion of ibuprofen is virtually complete 24 hours after the last dose. it has a biphasic plasma elimination time curve with a half-life of approximately 2 hours. there is no difference in the observed terminal elimination rate or half-life between children and adults, however, there is an age- or fever-related change in total clearance. this suggests that the observed change in clearance is due to changes in the volume of distribution of ibuprofen (see table 1 for cl/f values).

ever reduction resembled that seen in children treated with 5 mg/kg of ibuprofen, with the exception that temperature elevation tended to return 1 to 2 hours earlier. in patients with primary dysmenorrhea, ibuprofen has been shown to reduce elevated levels of prostaglandin activity in the menstrual fluid and to reduce testing and active intrauterine pressure, as well as the frequency of uterine contractions. the probable mechanism of action is to inhibit prostaglandin synthesis rather than simply to provide analgesia.

ding epigastric pain, dyspepsia, melena, and hematemesis. patients should be apprised of the importance of this follow-up (see warnings, gastrointestinal effects-risk of ulceration, bleeding, and perforation ). serious skin reactions, including dress advise patients to stop taking ibuprofen oral suspension immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible (see warnings ). 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 of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). if these occur, patients should be instructed to stop therapy and seek immediate medical therapy. patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). if these occur, patients should be instructed to seek immediate emergency help (see warnings ). fetal toxicity inform pregnant women to avoid use of ibuprofen oral suspension 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 oral suspension 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 (see warnings; fetal toxicity , precautions; pregnancy ).