Ibuprofen Liquid Gel Capsules 200 mg

Adults over 12 years
IBUPROFEN LIQUID GEL-CAPS (Ibuprofen) is indicated for treatment of pain associated with migraine.

IBUPROFEN LIQUID GEL-CAPS is also indicated for headaches and the temporary relief of menstrual pain (dysmenorrhea), toothache (dental pain), minor aches and pains in muscles, bones and joints and for reduction of fever and for temporary relief of mild to moderate pain.

Pediatrics
Studies conducted to date have not demonstrated pediatric-specific problems that would limit the usefulness of ibuprofen in children 6 months and older.

Ibuprofen is not recommended for use in patients under 2 months of age since safety and effectiveness have not been established.

Geriatrics
Patients older than 65 years and frail or debilitated patients are most susceptible to a variety of adverse reactions from nonsteroidal anti-inflammatory drugs (NSAIDs): the incidence of these adverse reactions increases with dose and duration of treatment. In addition, these patients are less tolerant to ulceration and bleeding. Most reports of fatal GI events are in this population. Older patients are also at risk of lower oesophageal ulceration and bleeding.

For such patients, consideration should be given to a starting dose lower than the one usually recommended, with individual adjustment when necessary and under close supervision. See "Gastrointestinal (GI)-Warnings and Precautions" for further advice.

Sore Throat Pain
A double-blind, randomized study showed that ibuprofen 400 mg relieved sore throat pain significantly better than placebo and acetaminophen.

Headache
A double-blind, randomized study showed that ibuprofen 400 mg relieved headache pain significantly better than acetaminophen 1000 mg and placebo. Another double-blind, placebo-controlled, randomized study showed that ibuprofen 400 mg began to exert a significant analgesic effect on headache within 30 minutes after dosing.

Dental Pain
A double-blind, randomized study showed that ibuprofen 400 mg relieved dental pain following removal of impacted third molars significantly better than acetaminophen and placebo. Several other comparative dental studies have described similar results.

Muscle Aches
A double-blind, randomized study showed that ibuprofen 400 mg every four hours for a total of three doses relieved muscle soreness following exercise significantly better than acetaminophen 1000 mg and placebo every four hours.

Dysmenorrhea
Several studies demonstrate the significant effect of ibuprofen compared to placebo or other active analgesics on uterine pain and cramping.

Fever
The antipyretic efficacy of ibuprofen has been demonstrated in adult.

SERIOUS WARNINGS AND PRECAUTIONS
History of peptic ulcers, gastrointestinal bleeding or other diseases of the gastrointestinal tract.

General
In common with other anti-inflammatory drugs, ibuprofen may mask the usual signs of infection.

Cardiovascular
Congestive heart failure in patients with marginal cardiac function, elevated blood pressure and palpitations.

Endocrine and Metabolism
Fluid retention and oedema have been observed in patients treated with ibuprofen. Therefore, as with many other nonsteroidal anti-inflammatory drugs, the possibility of precipitating congestive heart failure in elderly patients or those with compromised cardiac function should be borne in mind. IBUPROFEN LIQUID GEL-CAPS (Ibuprofen) should be used with caution in patients with heart failure, hypertension or other conditions predisposing to fluid retention.

With nonsteroidal anti-inflammatory treatment there is a potential risk of hyperkalemia, particularly in patients with conditions such as diabetes mellitus or renal failure; elderly patients; or in patients receiving concomitant therapy with B-adrenergic blockers, angiotensin converting enzyme inhibitors or some diuretics. Serum electrolytes should be monitored periodically during long-term therapy, especially in those patients who are at risk.

Gastrointestinal (GI)
Serious GI toxicity, such as peptic ulceration, perforation and gastrointestinal bleeding, sometimes severe and occasionally fatal, can occur at any time, with or without symptoms in patients treated with NSAIDs including ibuprofen.

Minor upper GI problems, such as dyspepsia, are common, usually developing early in therapy. Physicians should remain alert for ulceration and bleeding in patients treated with non-steroidal anti-inflammatory drugs, even in the absence of previous GI tract symptoms.

In patients observed in clinical trials of such agents, symptomatic upper GI ulcers, gross bleeding, or perforation appear to occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. The risk continues beyond one year and possibly increases. The incidence of these complications increases with increasing dose.

IBUPROFEN LIQUID GEL-CAPS should be given under close medical supervision to patients prone to gastrointestinal tract irritation, particularly those with a history of peptic ulcer, diverticulosis or other inflammatory disease of the gastrointestinal tract such as ulcerative colitis and Crohn's disease. In these cases the physician must weigh the benefits of treatment against the possible hazards.

Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and instruct them to contact a physician immediately if they experience persistent dyspepsia or other symptoms or signs suggestive of gastrointestinal ulceration or bleeding. Because serious GI tract ulceration and bleeding can occur without warning symptoms, physicians should follow chronically treated patients by checking their haemoglobin periodically and by being vigilant for the signs and symptoms of ulceration and bleeding and should inform the patients of the importance of this follow-up.

If ulceration is suspected or confirmed, or if GI bleeding occurs, IBUPROFEN LIQUID GEL-CAPS should be discontinued immediately, appropriate treatment instituted and the patient monitored closely.

No studies, to date, have identified any group of patients not at risk of developing ulceration and bleeding. A prior history of serious GI events and other factors such as excess alcohol intake, smoking, age, female gender and concomitant oral steroid and anticoagulant use have been associated with increased risk. Studies to date show that all NSAIDs can cause GI tract adverse events. Although existing data does not clearly identify differences in risk between various NSAIDs, this may be shown in the future.

There is no definitive evidence that the concomitant administration of histamine H2-receptor antagonists and/or antacids will either prevent the occurrence of gastrointestinal side effects or allow the continuation of IBUPROFEN LIQUID GEL-CAPS therapy when and if these adverse reactions appear.

Genitourinary
Some NSAIDs are known to cause persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy with an NSAID. Some cases have become severe on continued treatment. Should urinary symptoms occur, treatment with IBUPROFEN LIQUID GEL-CAPS must be stopped immediately to obtain recovery. This should be done before any urological investigations or treatments are carried out.

Haematologic
Drugs inhibiting prostaglandin biosynthesis do interfere with platelet function to varying degrees; therefore, patients who may be adversely affected by such an action should be carefully observed when ibuprofen is administered.

Blood dyscrasias (such as neutropenia, leukopenia, thrombocytopenia, aplastic anaemia and agranulocytosis) associated with the use of non-steroidal anti-inflammatory drugs are rare, but could occur with severe consequences.

Hepatic/ Biliary/Pancreatic
As with other nonsteroidal anti-inflammatory drugs, borderline elevations of one or more liver function tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with this drug. Severe hepatic reactions including jaundice and cases of fatal hepatitis have been reported with nonsteroidal anti-inflammatory drugs.

Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), this drug should be discontinued.

During long-term therapy, liver function tests should be monitored periodically. If there is a need to prescribe this drug in the presence of impaired liver function, it must be done under strict observation.

The frequency of acute liver injury among 625,307 people who received NSAIDs in England and Wales between 1987 and 1991, was examined. There were 311,716 patients who were prescribed ibuprofen. The incidence of acute liver injury among ibuprofen users was 1.6/100,000; this was the lowest incidence among the 8 NSAIDs studied and was significantly lower than the incidence among users of ketoprofen, piroxicam, fenbrufen, or sulindac. For NSAID users as a group, the only factors that had an independent effect on the occurrence of acute liver injury were the simultaneous use of hepatotoxic medication or the presence of rheumatoid arthritis. Based on these data, the short-term use of ibuprofen as an analgesic/antipyretic should not be of concern regarding the development of liver disease.

Immune
In occasional cases, with some NSAIDs, the symptoms of aseptic meningitis (stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissue diseases, etc.) seem to be pre-disposed. Therefore, in such patients, the physician must be vigilant to the development of this complication.

Skin
Some people may become more sensitive to sunlight than they are normally. Brief exposure to sunlight or sunlamps may cause sunburn, blisters on the skin, skin rash, redness, itching or discoloration or vision changes.

Neurologic
Some patients may experience drowsiness, dizziness, vertigo, insomnia or depression with the use of ibuprofen. If patients experience these side effects, they should exercise caution in carrying out activities that require alertness.

Ophthalmologic
Blurred and/or diminished vision has been reported with the use of ibuprofen and other non-steroidal anti-inflammatory drugs. If such symptoms develop this drug should be discontinued and an ophthalmologic examination performed; ophthalmic examination should be carried out at periodic intervals in any patient receiving this drug for an extended period of time.

Renal
Long term administration of nonsteroidal anti-inflammatory drugs to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with hematuria, proteinuria, and occasionally nephrotic syndrome.

A second form of renal toxicity has been seen in patients with prerenal conditions leading to the reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive 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 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 the elderly. Discontinuation of nonsteroidal anti-inflammatory therapy is usually followed by recovery to the pre-treatment state.

Ibuprofen and its metabolites are eliminated primarily by the kidneys; therefore the drug should be used with great caution in patients with impaired renal function. In these cases, utilization of lower doses of IBUPROFEN LIQUID GEL-CAPS should be considered and patients carefully monitored.

During long-term therapy kidney function should be monitored periodically.

Sensitivity/Resistance
Patients sensitive to any one of the nonsteroidal anti-inflammatory drugs may be sensitive to any of the other NSAIDs also.

Special Populations

Pregnant Women
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. Because of the known effects of NSAIDs on the fetal cardiovascular system, use of ibuprofen during late pregnancy should be avoided. As with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia and delayed parturition occurred in rats. Administration of ibuprofen is not recommended during pregnancy.

Nursing Women
The high protein binding and lower pH of breast milk versus plasma tend to inhibit the excretion of ibuprofen into breast milk. One study showed an ibuprofen concentration of 13 ng/mL 30 minutes after ingesting 400 mg. The milk: plasma ratio was 1:126. This translates to an infant exposure of 0.0008% of the maternal dose. It is not known to what extent, if any, ibuprofen crosses the human placenta.

Acetylsalicylic acid (ASA) or other NSAIDs
The use of IBUPROFEN LIQUID GEL-CAPS (Ibuprofen) in addition to any other NSAID, including ASA, is not recommended due to the possibility of additive side effects. Animal studies show that aspirin given with NSAIDs, including ibuprofen, yields a net decrease in anti-inflammatory activity with lowered blood levels of the non-aspirin drug. Single-dose bioavailability studies in normal volunteers have failed to show an effect of aspirin on ibuprofen blood levels. Correlative clinical studies have not been conducted.

Acetaminophen
Although interactions have not been reported, concurrent use with IBUPROFEN LIQUID GEL-CAPS is not advisable: it may increase the risk of adverse renal effect.

Digoxin
Ibuprofen has been shown to increase serum digoxin concentration. Increased monitoring and dosage adjustments of digitalis glycoside may be necessary during and following concurrent ibuprofen therapy.

Coumarin-type
Numerous studies have shown that the concomitant use of NSAIDs and anticoagulants increases the risk of GI adverse events such as ulceration and bleeding. Because prostaglandins play an important role in hemostasis, and NSAIDs affect platelet function, concurrent therapy of ibuprofen with warfarin requires close monitoring to be certain that no change in anticoagulant dosage is necessary. Several short-term controlled studies failed to show that ibuprofen significantly affected prothrombin time or a variety of other clotting factors when administered to individuals on coumarin-type anticoagulants. Nevertheless, the physician, should be cautious when administering IBUPROFEN LIQUID GEL-CAPS to patients on anticoagulants.

Hypoglycaemic Agents
Ibuprofen may increase hypoglycaemic effects of oral antidiabetic agents and insulin.

Antihypertensives
Prostaglandins are an important factor in cardiovascular homeostasis and inhibition of their synthesis by NSAIDs may interfere with circulatory control. NSAIDs may elevate blood pressure in patients receiving antihypertensive medication. Two meta analyses have observed this relationship for NSAIDs as a class and for certain NSAIDs in particular, but ibuprofen did not significantly affect blood pressure in either meta analysis. Consistent with this lack of effect, a study by Davies et al. showed that ibuprofen 1600 mg/day for 14 days did not attenuate the antihypertensive effect of two ß-adrenergic blockers. Houston et al.showed no effect of three weeks' therapy with ibuprofen on the antihypertensive efficacy of verapamil, but it is not known whether this lack of interaction extends to other classes of calcium channel blockers.

When renal perfusion pressure is reduced both prostaglandins and angiotensin II are important mediators of renal autoregulation. As a class, the combination of an NSAID and angiotensin converting enzyme inhibitor theoretically may have the potential to decrease renal function. One study found a clinically significant decrease in renal function in 4 of 17 patients treated with hydrochlorothioazide and fosinopril who received ibuprofen 2400 mg/day for one month. In contrast, Minuz found no effect on the antihypertensive effect of enalapril or on plasma renin or aldosterone following two days' treatment with ibuprofen 1200 mg/day.

The relationship of ibuprofen and antihypertensives is clearly not well defined. The benefits of concomitant medication should be analyzed and compared to the potential risks before being prescribed. If ibuprofen is being recommended for long-term use, then periodic monitoring of blood pressure may be useful. Blood pressure monitoring is not necessary if ibuprofen is being recommended for short-term use as an analgesic.

Diuretics
Clinical studies, as well as random 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 ibuprofen, the patient should be observed closely for signs of renal failure as well as to assure diuretic efficacy.

Antacids
A bioavailability study has shown that there was no interference with the absorption of ibuprofen when given in conjunction with an antacid containing aluminium 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.

Methotrexate
Ibuprofen as well as other NSAIDs has been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that ibuprofen could enhance the toxicity of methotrexate. Caution should be used when ibuprofen is administered concomitantly with methotrexate.

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.

Other Drugs
Although ibuprofen binds extensively to plasma proteins, interactions with other protein-bound drugs occur rarely. Nevertheless, caution should be observed when other drugs, also having a high affinity for protein binding sites, are used concurrently. No interactions have been reported when ibuprofen has been used in conjunction with probenecid, thyroxine, steroids, antibiotics or benzodiazepines.

Drug-Food Interactions
Interactions with food have not been established.

Drug-Herb Interactions
Interactions with herbal products have not been established.

Drug-Laboratory Interactions
Interactions with laboratory tests have not been established.

1. Active peptic ulcer, a history of recurrent ulceration or active inflammatory disease of the gastrointestinal system.
2. Known or suspected hypersensitivity to the drug or other non-steroidal anti-inflammatory drugs. The potential for cross-reactivity between different NSAIDs must be kept in mind.
3. IBUPROFEN LIQUID GEL-CAPS should not be used in patients with the complete or partial syndrome of nasal polyps, or in whom asthma, anaphylaxis, urticaria, rhinitis or other allergic manifestations are precipitated by ASA or other nonsteroidal anti-inflammatory agents. Fatal anaphylactoid reactions have occurred in such individuals. As well, individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse effects.
4. Significant hepatic impairment or active liver disease.
5. Severely impaired or deteriorating renal function (creatinine clearance <30 mL/min). Individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored.
6. Ibuprofen is not recommended for use with other NSAIDs because of the absence of any evidence demonstrating synergistic benefits and the potential for additive side effects.
7. Children with kidney disease and children who have suffered significant fluid loss should not be given ibuprofen.
8. Patients who are hypersensitive to the drug or to any ingredients in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.

Prescription Experience

The following adverse reactions have been noted in patients treated with prescription doses (≥1200 mg/day).

Note: Reactions listed below under Causal Relationship Unknown are those which occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, the possibility of a relationship to ibuprofen cannot be excluded.

Gastrointestinal
The adverse reactions most frequently seen with prescribed ibuprofen therapy involve the gastrointestinal system.

Incidence 3 to 9%: nausea, epigastric pain, heartburn
Incidence 1 to 3%: diarrhoea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or pain, fullness of the gastrointestinal tract (bloating or flatulence).
Incidence less than 1%: gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal haemorrhage, melena, hepatitis, jaundice, abnormal liver function (SGOT, serum bilirubin and alkaline phosphatase).

Allergic
Incidence less than 1%: anaphylaxis (see Contraindications). Causal relationship unknown: fever, serum sickness, lupus erythematosus.

Central Nervous System
Incidence 3 to 9%: dizziness
Incidence 1 to 3%: headache, nervousness
Incidence less than 1%: depression, insomnia
Causal relationship unknown: paresthesias, hallucinations, dream abnormalities
Aseptic meningitis and meningoencephalitis, in one case accompanied by eosinophilia in the cerebrospinal fluid, have been reported in patients who took ibuprofen intermittently and did not have any connective tissue disease.

Dermatologic
Incidence 3 to 9%: rash (including maculopapular type).
Incidence 1 to 3%: pruritus
Incidence less than 1%: vesiculobullous eruptions, urticaria, erythema multiforme
Causal relationship unknown: alopecia, Stevens-Johnson syndrome.

Cardiovascular
Incidence less than 1%: congestive heart failure in patients with marginal cardiac function, elevated blood pressure.
Causal relationship unknown: arrhythmias (sinus tachycardia, sinus bradycardia, palpitations).

Special Senses
Incidence 1 to 3%: tinnitus
Incidence less than 1%: amblyopia (blurred and/or diminished vision, scotomata and/or changes in colour vision). Any patient with eye complaints during ibuprofen therapy should have an ophthalmological examination.
Causal relationship unknown: conjunctivitis, diplopia, optic neuritis.

Hematologic
Incidence less than 1%: leukopenia, and decreases in haemoglobin and hematocrit. Causal relationship unknown: haemolytic anaemia, thrombocytopenia, granulocytopenia, bleeding episodes (e.g., purpura, epistaxis, hematuria, menorrhagia).

Renal
Causal relationship unknown: decreased creatinine clearance, polyuria, azotemia. Like other non-steroidal anti-inflammatory drugs, ibuprofen inhibits renal prostaglandin synthesis, which may decrease renal function and cause sodium retention. Renal blood flow and glomerular filtration rate decreased in patients with mild impairment of renal function who took 1200 mg/day of ibuprofen for one week. Renal papillary necrosis has been reported. A number of factors appear to increase the risk of renal toxicity.

Hepatic
Incidence less than 1%: Hepatitis, jaundice, abnormal liver function (SGOT, serum bilirubin, and alkaline phosphatase).

Endocrine
Causal relationship unknown: gynecomastia, hypoglycaemic reaction. Menstrual delays of up to two weeks and dysfunctional uterine bleeding occurred in nine patients taking ibuprofen, 400 mg t.i.d., for three days before menses.

Metabolic
Incidence 1 to 3%: decreased appetite, oedema, fluid retention.
Fluid retention generally responds promptly to drug discontinuation (See Warnings and Precautions).

Non-Prescription Experience: Literature (at dosages ≤ 1200 mg/day)

One researcher conducted an extensive analysis of published data concerning the relative safety of non-prescription doses of ibuprofen and acetaminophen. Of a total of 96 randomized and blinded trials, there were 10 trials of seven days' duration or less where the safety of both drugs was directly compared. In three of these trials, the incidence of adverse events was higher with acetaminophen; there were no reported adverse events in six trials; and one trial reported a higher incidence with ibuprofen. In this subset of 10 studies, it was reported that gastrointestinal adverse events were found to be the most common type of event reported and were predominantly dyspepsia, nausea, or vomiting. None of the GI events appeared to warrant follow-up from which the author inferred there were no serious gastrointestinal events.

It was concluded: "Although we recognize that the above mentioned data are very selective and are based on information derived from a variety of trial designs and populations, it is nonetheless instructive for indicating a relatively low incidence of severe adverse reactions with both drugs when taken at their respective non-prescription dosages."

A double-blind, placebo-controlled study (N=1246) was conducted to prospectively evaluate the gastrointestinal tolerability, as compared to placebo, of the maximum non¬prescription dose and duration (1200 mg/day for 10 consecutive days) of ibuprofen use in healthy subjects representative of a non-prescription analgesic user population. Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion of discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by ≥1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments. When used as directed to treat episodic pain, non¬prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well-tolerated.

In two multi-trial analyses a meta analysis, and a literature review, single doses of ibuprofen had a low incidence of gastrointestinal drug reactions, comparable to that of acetaminophen and placebo. Reports from spontaneous reporting systems in the United Kingdom, France and the United States, where a prescription is not needed for ibuprofen at a daily dose up to 1200 mg, confirm the medication's gastrointestinal safety and acceptability. A recently-completed large-scale randomized trial comparing non¬prescription doses of acetylsalicylic acid, acetaminophen, and ibuprofen in 8677 adults found that the rates of significant adverse reactions were: aspirin 18.7%, ibuprofen 13.7%, and acetaminophen 14.5%.

Ibuprofen was not statistically different from acetaminophen. Total gastrointestinal events (including dyspepsia) and abdominal pain were less frequent with ibuprofen (4% and 2.8%, respectively) than with acetaminophen (5.3% and 3.9%) or aspirin (7.1% and 6.8%) [all p< 0.035]. It was concluded that "The overall tolerability of ibuprofen in this large-scale study was equivalent to that of paracetamol and better than that of [ASA]."

The toxicity of ibuprofen overdose is dependent upon the amount of drug ingested and the time elapsed since ingestion; individual responses may vary, thus making it necessary to evaluate each case separately. Although uncommon, serious toxicity and death have been reported with ibuprofen overdosage. The most frequently reported symptoms of ibuprofen overdose include abdominal pain, nausea, vomiting, lethargy and drowsiness. Other CNS symptoms include headache, tinnitus, CNS depression and seizures. Metabolic acidosis, coma, acute renal failure and apnoea (primarily in very young pediatric patients) may rarely occur. Cardiovascular toxicity, including hypotension, bradycardia, tachycardia and atrial fibrillation, also have been reported.

Treatment of Overdose
In cases of acute overdose, the stomach should be emptied through induction of emesis (in alert patients only) or gastric lavage. Emesis is most effective if initiated within 30 minutes of ingestion. Orally administered activated charcoal may help in reducing the absorption of ibuprofen when given less than 2 hours following ingestion. There is some evidence that repeated administration of activated charcoal may bind the medication that has diffused from the circulation. Inducing diuresis may be helpful. The treatment of acute overdose is primarily supportive. Management of hypotension, acidosis and gastrointestinal bleeding may be necessary.

In pediatric patients, the estimated amount of ibuprofen ingested per body weight may be helpful to predict the potential for development of toxicity although each case must be evaluated. Ingestion of less than 100 mg/kg is unlikely to produce toxicity. Pediatric patients ingesting 100 to 200 mg/kg may be managed with induced emesis and a minimal observation time of at least four hours. Pediatric patients ingesting 200 to 400 mg/kg of ibuprofen should have immediate gastric emptying and at least four hours observation. Pediatric patients ingesting greater than 400 mg/kg require immediate medical referral, careful observation and appropriate supportive therapy. Induced emesis is not recommended in overdoses greater than 400 mg/kg because of the risk for convulsions and the potential for aspiration of gastric contents.

In adult patients, the dose reportedly ingested does not appear to be predictive of toxicity. The need for referral and follow-up must be judged by the circumstances at the time of the overdose ingestion. Symptomatic adults should be carefully evaluated, observed and supported.

Examples Of Ibuprofen Overdose
A 41-year-old man with multiple medical problems, including long-term renal insufficiency, developed near-fatal acute renal failure after ingestion of a massive dose (36 g) of ibuprofen [1]. He required dialysis for several months, at which point his renal function improved.

In children, ibuprofen overdoses less than 100 mg/kg are unlikely to produce toxicity. In adults, the dose of ibuprofen reportedly ingested does not appear to be predictive of toxicity.

With electrolyte replacement and other intensive measures, a 21-month-old child recovered within 5 days after accidental ingestion of 8 g of ibuprofen [2]. A 2-year-old child who ingested approximately 8g of ibuprofen was treated with activated charcoal, developed metabolic acidosis and acute renal insufficiency, and recovered within 72 hours [3]. A 6-year-old child became comatose after ingesting 6g of ibuprofen [4]. He was treated with gastric lavage, charcoal, and various supportive measures and recovered within 24 hours.