Ibuprofen

INDICATIONS AND USAGE Carefully consider the potential benefits and risks of Ibuprofen Oral Suspension and other treatment options before deciding to use Ibuprofen Oral Suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). In Pediatric Patients, Ibuprofen Oral Suspension is indicated: • For reduction of fever in patients aged 6 months up to 2 years of age. • For relief of mild to moderate pain in patients aged 6 months up to 2 years of age. • For relief of signs and symptoms of juvenile arthritis. In Adults, Ibuprofen Oral Suspension is indicated: • For treatment of primary dysmenorrhea. • For relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Since there have been no controlled trials to demonstrate whether there is any beneficial effect or harmful interaction with the use of ibuprofen in conjunction with aspirin, the combination cannot be recommended (see PRECAUTIONS - Drug Interactions ).

Purposes Pain reliever/fever reducer

DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of ibuprofen oral suspension and other treatment options before deciding to use ibuprofen oral suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). After observing the response to initial therapy with ibuprofen oral suspension, the dose and frequency should be adjusted to suit an individual patient’s needs. Pediatric Patients Fever Reduction : For reduction of fever in children, 6 months up to 2 years of age, the dosage should be adjusted on the basis of the initial temperature level (see CLINICAL PHARMACOLOGY ). The recommended dose is 5 mg/kg if the baseline temperature is less than 102.5oF, or 10 mg/kg if the baseline temperature is 102.5oF or greater. The duration of fever reduction is generally 6 to 8 hours. The recommended maximum daily dose is 40 mg/kg. Analgesia: For relief of mild to moderate pain in children 6 months 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 mg/kg/day 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 mg 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 oral suspension 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 …

CONTRAINDICATIONS Ibuprofen oral suspension is contraindicated in patients with known hypersensitivity to ibuprofen. Ibuprofen oral suspension should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDS have been reported in such patients (see WARNINGS – Anaphylactoid Reactions, and PRECAUTIONS – Preexisting Asthma ). Ibuprofen oral suspension is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).

Do not use • if the child has ever had an allergic reaction to ibuprofen or any other pain reliever/fever reducer • right before or after heart surgery

Ask a doctor before use if • stomach bleeding warning applies to your child • child has a history of stomach problems, such as heartburn • child has problems or serious side effects from taking pain relievers or fever reducers • child has not been drinking fluids • child has lost a lot of fluid due to vomiting or diarrhea • child has high blood pressure, heart disease, liver cirrhosis, kidney disease, or had a stroke • child has asthma • child is taking a diuretic

Stop use and ask a doctor if • child experiences any of the following signs of stomach bleeding: • feels faint • vomits blood • has bloody or black stools • has stomach pain that does not get better • child has symptoms of heart problems or stroke: • chest pain • trouble breathing • weakness in one part or side of body • slurred speech • leg swelling • the child does not get any relief within first day (24 hours) of treatment • fever or pain gets worse or lasts more than 3 days • redness or swelling is present in the painful area • any new symptoms appear

ADVERSE REACTIONS In patients taking ibuprofen or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are: Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, fluid retention, gastrointestinal experiences (including abdominal pain, bloating, constipation, diarrhea, dyspepsia, epigastric pain, flatulence, heartburn, nausea, vomiting), headaches, increased bleeding time, nervousness, pruritus, rashes (including maculopapular) and tinnitus. Additional adverse experiences reported occasionally include: Body as a whole - fever, infection, sepsis Cardiovascular system - congestive heart failure in patients with marginal cardiac function, hypertension, tachycardia, syncope Digestive system - dry mouth, duodenitis, esophagitis, gastric or duodenal ulcer with bleeding and/or perforation, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice, melena, rectal bleeding Hemic and lymphatic system - 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 liability hallucinations, aseptic meningitis Respiratory - apnea, respiratory depression, pneumonia, rhinitis Skin and appendages - angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, Stevens Johnson Syndrome, fixed drug eruption (FDE), 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 Sun Pharmaceutical Industries, 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.

Drug Interactions ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors. Aspirin Pharmacodynamic studies have demonstrated interference with the antiplatelet activity of aspirin when ibuprofen 400 mg, given three times daily, is administered with enteric-coated low-dose aspirin. The interaction exists even following a once-daily regimen of ibuprofen 400 mg, particularly when ibuprofen is dosed prior to aspirin. The interaction is alleviated if immediate-release low-dose aspirin is dosed at least 2 hours prior to a once-daily regimen of ibuprofen; however, this finding cannot be extended to enteric-coated low-dose aspirin [see Clinical Pharmacology/Pharmacodynamics]. Because there may be an increased risk of cardiovascular events due to the interference of ibuprofen with the antiplatelet effect of aspirin, for patients taking low-dose 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 oral suspension 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.

DESCRIPTION The active ingredient in Ibuprofen oral suspension, USP 100 mg/5 mL is ibuprofen, which is a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen is a racemic mixture of [+]S- and [-]R-enantiomers. It is a white to off-white, crystalline powder, with a melting point of 75° to 78°C. It is practically insoluble in water (<0.1 mg/mL), but readily soluble in organic solvents such as ethanol and acetone. Ibuprofen has a pKa of 4.43±0.03 and an n-octanol/water partition coefficient of 11.7 at pH 7.4. The chemical name for ibuprofen is (±)-2-(p-isobutylphenyl) propionic acid. The molecular weight of ibuprofen is 206.28. Its molecular formula is C 13 H 18 O 2 and it has the following structural formula: Ibuprofen oral suspension, USP 100 mg/5 mL is a sucrose-sweetened, pale yellow to orange color suspension with mixed berry flavor, containing 100 mg of ibuprofen in 5 mL (20 mg/mL). Inactive ingredients include: acesulfame potassium, anhydrous citric acid, D&C yellow #10, FD&C red #40, glycerin, hypromellose, mix berry flavor (natural and artificial flavor and propylene glycol), polysorbate 80, purified water, sodium benzoate, sucrose and xanthan gum. Image

Active ingredient (in each 5 mL = 1 teaspoonful) Ibuprofen 100 mg (NSAID)* *nonsteroidal anti-inflammatory drug

OVERDOSAGE The toxicity of ibuprofen overdose is dependent upon the amount of drug ingested and the time elapsed since ingestion, though individual response may vary, which makes it necessary to evaluate each case individually. Although uncommon, serious toxicity and death have been reported in the medical literature with ibuprofen overdosage. The most frequently reported symptoms of ibuprofen overdose include abdominal pain, nausea, vomiting, lethargy and drowsiness. Other central nervous system symptoms include headache, tinnitus, CNS depression and seizures. Metabolic acidosis, coma, acute renal failure and apnea (primarily in very young children) may rarely occur. Cardiovascular toxicity, including hypotension, bradycardia, tachycardia and atrial fibrillation, also have been reported. The treatment of acute ibuprofen overdose is primarily supportive. Management of hypotension, acidosis and gastrointestinal bleeding may be necessary. In cases of acute overdose, the stomach should be emptied through ipecac-induced emesis or lavage. Emesis is most effective if initiated within 30 minutes of ingestion. Orally administered activated charcoal may help in reducing the absorption and reabsorption of ibuprofen. In children, 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. Children ingesting 100 to 200 mg/kg may be managed with induced emesis and a minimal observation time of four hours. Children ingesting 200 to 400 mg/kg of ibuprofen should have immediate gastric emptying and at least four hours observation in a health care facility. Children ingesting greater than 400 mg/kg require immediate medical referral, careful observation and appropriate supportive therapy. Ipecac-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 history of 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.

HOW SUPPLIED Ibuprofen oral suspension USP, 100 mg/5 mL is light orange to orange colored, berry flavored suspension. Bottles of 4 fl oz (120 mL) NDC 59651-032-12 Bottles of 16 fl oz (473 mL) NDC 59651-032-47 Shake well before using. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a well-closed container as defined in the USP. Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 08/2024 Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides