Ibuprofen

Description

The active ingredient in Ibuprofen oral suspension, USP 100 mg/5 mL is ibuprofen, a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen is a racemic mixture of +S- and -R-enantiomers. It appears as a white to off-white, crystalline powder with a melting point of 75° to 78°C. The compound is practically insoluble in water (<0.1 mg/mL) but is 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, with a molecular weight of 206.28 and a molecular formula of C13H18O2.

Ibuprofen oral suspension, USP 100 mg/5 mL is a sucrose-sweetened, pale yellow to orange color suspension with a 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, mixed berry flavor (natural and artificial flavor and propylene glycol), polysorbate 80, purified water, sodium benzoate, sucrose, and xanthan gum.

Uses and Indications

Ibuprofen oral suspension is indicated for use in pediatric patients and adults for the management of various conditions.

In pediatric patients aged 6 months to 2 years, ibuprofen oral suspension is indicated for the reduction of fever and for the relief of mild to moderate pain. Additionally, it is indicated for the relief of signs and symptoms associated with juvenile arthritis.

In adults, ibuprofen oral suspension is indicated for the treatment of primary dysmenorrhea and for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis.

There are no specific teratogenic or nonteratogenic effects associated with ibuprofen oral suspension.

Dosage and Administration

Pediatric patients requiring fever reduction should receive a recommended dose of 5 mg/kg if the baseline temperature is less than 102.5°F, and 10 mg/kg if the baseline temperature is 102.5°F or greater. The duration of fever reduction typically lasts for 6 to 8 hours, with a maximum daily dose not exceeding 40 mg/kg.

For analgesia in pediatric patients, the recommended dosage is 10 mg/kg administered every 6 to 8 hours, with the same maximum daily limit of 40 mg/kg. In cases of juvenile arthritis, the recommended dose ranges from 30 to 40 mg/kg/day, divided into three to four doses. Patients with milder disease may be treated with a lower dose of 20 mg/kg/day. It is important to note that doses exceeding 50 mg/kg/day are not recommended.

In adult patients experiencing primary dysmenorrhea, a dose of 400 mg may be taken every 4 hours as necessary. For those with rheumatoid arthritis and osteoarthritis, the suggested daily dosage ranges from 1200 to 3200 mg, which can be administered as 300 mg four times daily (q.i.d.) or in divided doses of 400 mg, 600 mg, or 800 mg three to four times daily (t.i.d. or q.i.d.).

Dosage for adults should be individualized, taking into account the severity of symptoms. Following a satisfactory response, the patient's dosage should be reviewed and adjusted as necessary to ensure optimal therapeutic outcomes.

Contraindications

Ibuprofen oral suspension is contraindicated in patients with known hypersensitivity to ibuprofen. It should not be administered to individuals who have a history of asthma, urticaria, or allergic-type reactions following the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been reported in these patients. Additionally, the use of ibuprofen oral suspension is contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is likely to escalate with prolonged use. It is crucial to note that ibuprofen oral suspension is contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs also pose a significant risk of serious gastrointestinal adverse events, such as bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These gastrointestinal complications can occur at any time during treatment and may arise without warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal events.

To mitigate the potential risk of adverse cardiovascular events in patients treated with NSAIDs, it is recommended to use the lowest effective dose for the shortest duration necessary. Both physicians and patients should remain vigilant for the development of cardiovascular events throughout the entire treatment course, even in the absence of prior cardiovascular symptoms. Patients should be educated on the signs and symptoms of serious cardiovascular events and the appropriate actions to take should they occur.

NSAIDs should be prescribed with caution in individuals with a history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding face more than a tenfold increased risk of developing gastrointestinal bleeding compared to those without these risk factors. Blood pressure should be monitored closely during the initiation of NSAID treatment and throughout the duration of therapy.

Healthcare professionals should monitor patients for signs or symptoms of gastrointestinal bleeding. For those on long-term NSAID therapy, periodic checks of complete blood count (CBC) and a chemistry profile are advised. If any clinical signs or symptoms indicative of liver or renal disease develop, or if systemic manifestations such as eosinophilia or rash occur, or if abnormal liver tests persist or worsen, ibuprofen oral suspension should be discontinued.

In cases of an anaphylactoid reaction, emergency medical assistance should be sought immediately. Patients should be informed about the signs and symptoms of serious skin reactions. They should discontinue the use of ibuprofen oral suspension at the first appearance of a skin rash or any other indication of hypersensitivity. If such signs or symptoms are present, it is imperative to discontinue ibuprofen oral suspension and evaluate the patient without delay.

Side Effects

Patients may experience a range of adverse reactions while using this medication, categorized by frequency and seriousness.

Common adverse reactions, occurring in 1 to 10% of patients, include abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, fluid retention, and various gastrointestinal symptoms such as abdominal pain, bloating, constipation, diarrhea, dyspepsia, epigastric pain, flatulence, heartburn, nausea, and vomiting. Additional common reactions include headaches, increased bleeding time, nervousness, pruritus, rashes (including maculopapular), and tinnitus.

Occasionally reported adverse reactions encompass a broader spectrum of effects. Systemic reactions may include fever, infection, and sepsis. Cardiovascular issues such as congestive heart failure in patients with marginal cardiac function, hypertension, tachycardia, and syncope have also been noted. Digestive system reactions may involve dry mouth, duodenitis, esophagitis, gastric or duodenal ulcers with bleeding and/or perforation, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice, melena, and rectal bleeding. Hematologic reactions include ecchymosis, eosinophilia, leukopenia, purpura, stomatitis, and thrombocytopenia. Metabolic and nutritional changes such as weight fluctuations, as well as nervous system effects including anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, paresthesia, somnolence, tremors, and vertigo, have been reported. Respiratory symptoms may include asthma and dyspnea. Skin reactions can manifest as alopecia, photosensitivity, and increased sweating. Additionally, blurred vision has been noted among special senses, while urogenital reactions may include cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, and acute renal failure in patients with pre-existing significantly impaired renal function.

Rare adverse reactions have also been documented. These include serious systemic reactions such as anaphylactic and anaphylactoid reactions, appetite changes, and cardiovascular events like arrhythmia, cerebrovascular accidents, hypotension, myocardial infarction, palpitations, and vasculitis. Digestive system reactions may involve eructation, gingival ulcers, hepatorenal syndrome, liver necrosis, liver failure, and pancreatitis. Hematologic concerns include agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, neutropenia, and pancytopenia. Metabolic issues such as hyperglycemia, as well as nervous system reactions including convulsions, coma, emotional lability, hallucinations, and aseptic meningitis, have been reported. Respiratory complications may include apnea, respiratory depression, pneumonia, and rhinitis. Skin and appendage reactions can be severe, including angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, fixed drug eruptions, urticaria, and vesiculobullous eruptions. Special senses may be affected by amblyopia, conjunctivitis, dry eyes, and hearing impairment. Urogenital reactions may include azotemia, decreased creatinine clearance, glomerulitis, renal papillary necrosis, and tubular necrosis.

It is important to note that there is an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with the duration of use. Additionally, there is an increased risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal.

Anaphylactoid reactions may occur in patients without known prior exposure to the medication. Serious skin adverse events, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which can be fatal, have been reported. Furthermore, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been documented, with some events being fatal or life-threatening, characterized by symptoms such as fever, rash, lymphadenopathy, and/or facial swelling.

Drug Interactions

The concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and various other medications may lead to significant drug interactions that warrant careful consideration.

Antihypertensive Agents NSAIDs may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors. Clinicians should monitor blood pressure and consider dosage adjustments of the antihypertensive agent as necessary.

Antiplatelet Agents Ibuprofen can interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered prior to aspirin. It is advisable to separate the dosing of these medications to maintain the efficacy of aspirin's antiplatelet effects.

Diuretics The use of ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics, which could potentially lead to renal failure. Monitoring of renal function is recommended in patients receiving this combination.

Lithium Ibuprofen has the potential to elevate plasma lithium levels and reduce its renal clearance, thereby increasing the risk of lithium toxicity. Regular monitoring of lithium levels is advised when these drugs are used concurrently.

Methotrexate NSAIDs may enhance the toxicity of methotrexate by competitively inhibiting its accumulation. Caution should be exercised when these agents are used together, and monitoring for signs of methotrexate toxicity is recommended.

Anticoagulants Caution is advised when ibuprofen is used in conjunction with warfarin due to an increased risk of serious gastrointestinal bleeding. Regular monitoring of coagulation parameters is recommended to mitigate this risk.

Packaging & NDC

The table below lists all NDC Code configurations of Ibuprofen, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of ibuprofen oral suspension have not been established in pediatric patients below the age of 6 months. For children aged 6 months and older, dosing should be guided by body weight to ensure appropriate administration.

Geriatric Use

Caution should be exercised when treating elderly patients (65 years and older) with this medication, as with any nonsteroidal anti-inflammatory drugs (NSAIDs). It is important for healthcare providers to consider the increased risk of adverse effects in this population. Monitoring for potential side effects and adjusting dosages as necessary may be warranted to ensure the safety and efficacy of treatment in geriatric patients.

Pregnancy

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen oral suspension, during pregnancy is associated with significant risks, particularly when used after approximately 20 weeks of gestation. The administration of NSAIDs at about 30 weeks gestation or later increases the risk of premature closure of the fetal ductus arteriosus, which can lead to serious fetal complications. Additionally, NSAID use during this period has been linked to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment.

Healthcare professionals are advised to limit the dose and duration of ibuprofen oral suspension use between approximately 20 and 30 weeks of gestation. If NSAID treatment is deemed necessary after 20 weeks, it should be restricted to the lowest effective dose for the shortest duration possible. Should treatment extend beyond 48 hours, monitoring with ultrasound for oligohydramnios is recommended. In instances where oligohydramnios is detected, ibuprofen oral suspension should be discontinued, and appropriate follow-up should be conducted according to clinical practice guidelines.

While animal studies have not demonstrated developmental abnormalities, the relevance of these findings to human pregnancies remains uncertain. Prostaglandins play a crucial role in fetal kidney development and other reproductive processes; therefore, the use of prostaglandin synthesis inhibitors like ibuprofen may impair kidney development when administered at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2 to 4% and 15 to 20%, respectively. However, the background risk of major birth defects and miscarriage for the indicated population(s) using ibuprofen is unknown. There are no adequate, well-controlled studies in pregnant women, and ibuprofen should only be used during pregnancy if the potential benefits justify the potential risks to the fetus.

Published literature indicates that adverse outcomes, such as fetal renal dysfunction leading to oligohydramnios, may occur after days to weeks of NSAID treatment, although some cases of oligohydramnios have been reported as soon as 48 hours after initiation. While many cases of decreased amniotic fluid were transient and reversible upon cessation of the drug, there have been limited reports of irreversible neonatal renal dysfunction requiring invasive interventions.

Due to methodological limitations in postmarketing studies, including the absence of control groups and insufficient data on dosage and duration of exposure, establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use remains challenging. Furthermore, the generalizability of reported risks to full-term infants exposed to NSAIDs through maternal use is uncertain, as most safety data pertain to preterm infants.

Lactation

It is not known whether this drug is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants from ibuprofen oral suspension, lactating mothers should consider the importance of the drug to their health when making a decision to either discontinue nursing or discontinue the drug.

Renal Impairment

Long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with renal papillary necrosis and other forms of renal injury. In patients with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs in these individuals may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and precipitate overt renal decompensation.

Patients at the highest risk for these adverse effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

There is no available information from controlled clinical studies regarding the use of ibuprofen oral suspension in patients with advanced renal disease; therefore, its use is not recommended in this population. If therapy with ibuprofen oral suspension is deemed necessary, close monitoring of the patient's renal function is advised.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when administered nonsteroidal anti-inflammatory drugs (NSAIDs). Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. In patients with compromised liver function, there is a potential for renal toxicity due to the role of renal prostaglandins in maintaining renal perfusion. The use of NSAIDs in these patients may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and precipitate overt renal decompensation.

Patients at greatest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. It is essential to monitor renal function closely in patients with hepatic impairment who are prescribed NSAIDs. Should any signs of renal decompensation occur, discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state. Therefore, careful consideration of the risks and benefits is warranted when prescribing NSAIDs to patients with hepatic impairment.

Overdosage

The toxicity associated with ibuprofen overdose is contingent upon the quantity ingested and the duration since ingestion. Serious toxicity and fatalities have been documented in cases of overdose.

Symptoms of Overdosage Clinical manifestations of ibuprofen overdose may include abdominal pain, nausea, vomiting, lethargy, drowsiness, headache, tinnitus, central nervous system (CNS) depression, seizures, metabolic acidosis, coma, acute renal failure, and apnea. Additionally, cardiovascular complications may arise, presenting as hypotension, bradycardia, tachycardia, and atrial fibrillation.

Dosage Considerations Ingestion of less than 100 mg/kg of ibuprofen is generally not expected to result in toxicity. However, doses ranging from 100 to 200 mg/kg may necessitate observation. For doses between 200 to 400 mg/kg, immediate gastric emptying and observation are required. In children, ingestion of more than 400 mg/kg mandates urgent medical referral and careful monitoring; the use of ipecac to induce vomiting is not advised due to associated risks.

In adults, the relationship between the ingested dose and the potential for toxicity is not straightforward, as the history of the dose consumed does not reliably predict the severity of toxicity. Therefore, symptomatic adults should undergo thorough evaluation and supportive care.

Management of Overdosage The management of acute ibuprofen overdose is primarily supportive in nature. Treatment strategies may include addressing hypotension, metabolic acidosis, and gastrointestinal bleeding. Emesis is most effective when initiated within 30 minutes of ingestion, while the administration of activated charcoal may be beneficial in reducing absorption if given promptly.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen oral suspension, during pregnancy has been associated with teratogenic effects. Specifically, administration around 30 weeks gestation or later increases the risk of premature closure of the fetal ductus arteriosus. Additionally, use of NSAIDs from approximately 20 weeks gestation or later has been linked to fetal renal dysfunction, which can lead to oligohydramnios and, in some instances, neonatal renal impairment. Animal studies have demonstrated that the administration of prostaglandin synthesis inhibitors, such as ibuprofen, results in increased pre- and post-implantation loss. Prostaglandins play a crucial role in fetal kidney development, and published animal studies indicate that prostaglandin synthesis inhibitors can impair kidney development when given at clinically relevant doses.

There are no adequate, well-controlled studies in pregnant women; therefore, ibuprofen should be used during pregnancy only if the potential benefits justify the potential risks to the fetus. The estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is between 2 to 4% and 15 to 20%, respectively.

Animal reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities. However, it is important to note that animal reproduction studies are not always predictive of human response. In rat studies involving NSAIDs, similar to other drugs that inhibit prostaglandin synthesis, there was an increased incidence of dystocia, delayed parturition, and decreased pup survival.

Postmarketing Experience

Anemia has been reported in patients receiving NSAIDs, including ibuprofen oral suspension. This condition may arise from fluid retention, occult or gross gastrointestinal blood loss, or an incompletely described effect on erythropoiesis. It is recommended that patients undergoing long-term treatment with NSAIDs, including ibuprofen oral suspension, have their hemoglobin or hematocrit levels monitored if they exhibit any signs or symptoms of anemia.

In two postmarketing clinical studies, the incidence of decreased hemoglobin levels was found to be higher than previously documented. A decrease in hemoglobin of 1 gram or more was observed in 17.1% of 193 patients taking 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients taking 2400 mg of ibuprofen daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were noted in these studies.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients using NSAIDs such as ibuprofen oral suspension. Some of these cases have been fatal or life-threatening. DRESS typically presents with symptoms including fever, rash, lymphadenopathy, and/or facial swelling, and may also involve hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis.

A limited number of case reports have indicated maternal NSAID use associated with neonatal renal dysfunction, occurring without oligohydramnios, with some cases being irreversible. Certain instances of neonatal renal dysfunction necessitated invasive treatments, such as exchange transfusion or dialysis.

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as ibuprofen oral suspension, and periodically throughout the course of treatment. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be advised to be vigilant for symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately.

It is important to inform patients that ibuprofen oral suspension, like other NSAIDs, can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects such as ulcers and bleeding, which may lead to hospitalization or even death. Patients should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they observe any indicative signs or symptoms.

Patients should be advised 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, as serious skin reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), may occur.

Healthcare providers should inform patients to be aware of the symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms arise.

Patients should also be informed about the warning signs and symptoms of hepatotoxicity, which may include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms. If these symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

Additionally, patients should be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. If these symptoms occur, patients should be instructed to seek immediate emergency help.

Pregnant women should be informed to avoid the use of ibuprofen oral suspension and other NSAIDs starting at 30 weeks gestation due to the risk of premature closure of the fetal ductus arteriosus. If treatment with ibuprofen oral suspension is necessary for a pregnant woman between approximately 20 to 30 weeks gestation, she should be advised that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

Storage and Handling

The product is supplied in a well-closed container as defined by the United States Pharmacopeia (USP). It is essential to shake well before use to ensure proper mixing of the contents.

Storage conditions require the product to be maintained at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is crucial for maintaining the integrity and efficacy of the product.

Additional Clinical Information

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as serious ulcerations and bleeding can occur unexpectedly. For patients undergoing long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that complete blood counts (CBC) and chemistry profiles be assessed periodically to ensure safety.

In cases where patients exhibit clinical signs and symptoms indicative of liver or renal disease, such as eosinophilia or rash, or if there is a persistence or worsening of abnormal liver tests, the use of ibuprofen oral suspension should be discontinued promptly.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Ibuprofen as submitted by Strides Pharma Science Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)