Ibuprofen

Description

Ibuprofen tablets contain the active ingredient ibuprofen, which is (±)-2-(p-isobutylphenyl) propionic acid. Ibuprofen appears as a white powder with a melting point of 74 to 77° C. It is very slightly soluble in water (<1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone. Ibuprofen is available in 400 mg, 600 mg, and 800 mg tablets for oral administration. The inactive ingredients include colloidal silicon dioxide, croscarmellose sodium, hypromellose 2910, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, pregelatinized starch, povidone k-90, sodium lauryl sulphate, and titanium dioxide.

Uses and Indications

Ibuprofen tablets are indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Limitations of Use: Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have not been conducted. Therefore, the use of ibuprofen in pediatric populations should be approached with caution.

Dosage and Administration

For the treatment of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage ranges from 1,200 mg to 3,200 mg daily. This can be administered as 300 mg four times a day, or as 400 mg, 600 mg, or 800 mg three to four times a day. It is imperative not to exceed a total daily dose of 3,200 mg. The dosage should be individualized for each patient and may be adjusted according to the severity of symptoms.

For the management of mild to moderate pain, a dosage of 400 mg may be taken every 4 to 6 hours as needed for pain relief.

In cases of dysmenorrhea, a dosage of 400 mg can be administered every 4 hours as necessary for pain relief.

To minimize gastrointestinal discomfort, it is recommended that ibuprofen tablets be taken with meals or milk.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of ibuprofen is not recommended for individuals who have a history of asthma, urticarial, or allergic-type reactions following the administration of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been documented in these patients. Furthermore, ibuprofen tablets are contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Increased cardiovascular risks are associated with the use of NSAIDs, including a heightened likelihood of serious thrombotic events such as myocardial infarction (MI) and stroke, which may be fatal. These risks can manifest early in treatment and may escalate with prolonged use. Special caution is warranted in patients who have undergone coronary artery bypass graft (CABG) surgery, as NSAIDs are contraindicated in this setting due to an increased incidence of MI and stroke. Additionally, post-MI patients are at an elevated risk for reinfarction, cardiovascular-related mortality, and all-cause mortality when treated with NSAIDs.

Hypertension is another concern, as NSAIDs can induce new hypertension or exacerbate existing conditions. Therefore, it is imperative to monitor blood pressure closely during treatment. Patients with heart failure may experience an increased risk of hospitalization and mortality due to fluid retention and edema.

Gastrointestinal adverse events pose significant risks, including inflammation, bleeding, ulceration, and perforation, which can be fatal. Should any serious gastrointestinal events be suspected, NSAID therapy should be discontinued immediately. Long-term use of NSAIDs may also lead to renal injury, particularly in patients with preexisting renal impairment, necessitating close monitoring of renal function.

Anaphylactoid reactions can occur even in patients without prior exposure to NSAIDs; immediate emergency medical assistance should be sought in such cases. Serious skin reactions, including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported and can be fatal. If any signs of hypersensitivity or skin rash appear, the use of ibuprofen should be discontinued, and the patient should be evaluated promptly. Furthermore, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) may occur and can be life-threatening; ibuprofen should be stopped if any symptoms arise.

Fetal toxicity is a critical consideration, particularly in pregnant women at approximately 30 weeks gestation or later, due to the risk of premature closure of the fetal ductus arteriosus and potential renal dysfunction.

To minimize risks, it is recommended to use the lowest effective dose for the shortest duration necessary. Patients should be monitored for signs of cardiac ischemia, especially those with a recent MI. Blood pressure and renal function should be closely monitored throughout the course of NSAID therapy, particularly in patients with advanced renal disease.

Side Effects

Patients receiving treatment with this medication may experience a range of adverse reactions. Serious adverse reactions include an increased risk of cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is known to increase with prolonged use. Additionally, there is a significant risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal events can occur at any time during treatment and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Common adverse reactions, occurring in greater than 1% but less than 3% of patients, include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, abdominal distress, and constipation. Central nervous system effects may manifest as dizziness, headache, and nervousness. Dermatologic reactions may include rash (including maculopapular types) and pruritus. Other reported reactions include tinnitus, decreased appetite, edema, and fluid retention, which generally respond promptly to discontinuation of the drug.

Less common adverse reactions, with a precise incidence unknown but occurring in less than 1% of patients, may include serious gastrointestinal complications such as gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis. Central nervous system effects may also include depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Dermatologic reactions can range from vesiculobullous eruptions to severe conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Hematologic reactions may include neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia. Cardiovascular effects may involve congestive heart failure in patients with marginal cardiac function, elevated blood pressure, and palpitations. Renal complications such as acute renal failure and decreased creatinine clearance have also been reported.

Additional adverse reactions with an unknown causal relationship, occurring in less than 1% of patients, may include central nervous system symptoms such as paresthesias, hallucinations, and dream abnormalities. Dermatologic reactions may include toxic epidermal necrolysis and photoallergic skin reactions. Special senses may be affected by conditions such as conjunctivitis and diplopia. Hematologic issues may present as bleeding episodes, while metabolic/endocrine reactions could include gynecomastia and hypoglycemic reactions. Cardiovascular concerns may involve arrhythmias.

Postmarketing experience has revealed further dermatologic reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and fixed drug eruption.

Drug Interactions

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents, particularly angiotensin-converting enzyme (ACE) inhibitors, may result in diminished antihypertensive efficacy. It is advisable to monitor blood pressure closely in patients receiving this combination.

Ibuprofen has been shown to interfere with the antiplatelet effects of aspirin, particularly when ibuprofen is administered prior to aspirin. To mitigate this interaction, it is recommended that immediate-release low-dose aspirin be taken at least 2 hours before ibuprofen.

The natriuretic effect of diuretics such as furosemide and thiazides may be reduced by ibuprofen, which is attributed to its inhibition of renal prostaglandin synthesis. Clinicians should consider monitoring renal function and diuretic efficacy in patients receiving this combination.

In patients taking lithium, ibuprofen can elevate plasma lithium levels and decrease renal clearance, thereby increasing the risk of lithium toxicity. Regular monitoring of lithium levels is recommended for patients on this combination.

NSAIDs, including ibuprofen, may enhance the toxicity of methotrexate by competitively inhibiting its renal accumulation. Caution is warranted when these agents are used together, and monitoring for signs of methotrexate toxicity is advised.

When administering ibuprofen to patients on warfarin-type anticoagulants, caution is advised due to the potential risk of serious gastrointestinal bleeding. Close monitoring of coagulation parameters is recommended in these patients.

Co-administration of ibuprofen with cimetidine or ranitidine does not significantly affect ibuprofen serum concentrations, and no dosage adjustments are necessary in this context.

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

Safety and effectiveness of ibuprofen tablets in pediatric patients have not been established. Therefore, caution should be exercised when considering the use of ibuprofen in this population. Further studies are needed to determine appropriate dosing and outcomes in children.

Geriatric Use

Caution should be exercised when treating elderly patients, specifically those aged 65 years and older. Due to the potential for altered pharmacokinetics and increased sensitivity to medications in this population, careful consideration of dosage adjustments and monitoring is essential. Healthcare providers are advised to assess the individual health status and comorbidities of geriatric patients to ensure safe and effective treatment.

Pregnancy

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy is associated with potential risks to the fetus. Specifically, NSAID use can lead to premature closure of the fetal ductus arteriosus and fetal renal dysfunction, which may result in oligohydramnios and, in some cases, neonatal renal impairment. Due to these risks, it is recommended to limit the dose and duration of ibuprofen tablets use between approximately 20 and 30 weeks of gestation, and to avoid use at around 30 weeks of gestation and later in pregnancy.

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 specific background risk associated with ibuprofen tablets remains unknown. Observational studies regarding potential embryo-fetal risks of NSAID use during the first or second trimesters have yielded inconclusive results. Animal studies have not demonstrated developmental abnormalities with ibuprofen; however, these studies are not always predictive of human outcomes.

Prostaglandins play a crucial role in endometrial vascular permeability, blastocyst implantation, and fetal kidney development. In animal studies, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has been associated with increased pre- and post-implantation loss and impaired kidney development at clinically relevant doses. Therefore, if an NSAID is deemed necessary after 20 weeks of gestation, it should be used at the lowest effective dose for the shortest duration possible. If treatment extends beyond 48 hours, monitoring with ultrasound for oligohydramnios is advised. Should oligohydramnios occur, ibuprofen tablets should be discontinued, and follow-up should be conducted according to clinical practice.

Published literature indicates that the use of NSAIDs at around 30 weeks of gestation or later may lead to premature closure of the fetal ductus arteriosus. Maternal NSAID use during this period has been associated with fetal renal dysfunction and oligohydramnios, with some cases of neonatal renal impairment requiring invasive procedures. The timing and duration of NSAID exposure, as well as concomitant medication use, complicate the assessment of risk for adverse fetal and neonatal outcomes.

Additionally, animal studies have shown that NSAID use may result in increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown. It is also unclear whether ibuprofen is excreted in human milk. Given the potential for serious adverse reactions in nursing infants, a decision should be made regarding the continuation of nursing or the drug, considering the importance of ibuprofen to the mother.

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 tablets, 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 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 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 effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. In cases where NSAID therapy is initiated, close monitoring of renal function is advisable. 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 tablets in patients with advanced renal disease; therefore, treatment with ibuprofen tablets is not recommended in this population. If NSAID treatment is deemed necessary during pregnancy, particularly between 20 and 30 weeks gestation, it is important to limit the use of ibuprofen tablets to the lowest effective dose and shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if treatment extends beyond 48 hours, and ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up according to clinical practice.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a compensatory role in maintaining renal perfusion. In patients with compromised liver function, the administration of an NSAID may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate overt renal decompensation.

Patients at the highest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. Therefore, it is crucial to exercise caution when considering NSAID therapy in this population.

Currently, there is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Consequently, treatment with ibuprofen tablets is not recommended for patients with advanced renal disease. If therapy with ibuprofen tablets is deemed necessary, close monitoring of renal function is advised to mitigate potential risks. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of careful patient management.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the timing of intervention.

A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg). This child presented with apneic and cyanotic symptoms, necessitating the administration of oxygen and fluids. Blood analysis approximately 8½ hours post-ingestion revealed a concentration of 102.9 mcg/mL.

Conversely, in two separate instances, children weighing around 10 kg ingested approximately 120 mg/kg of ibuprofen without exhibiting acute intoxication symptoms. Notably, one child's blood level was measured at 700 mcg/mL just 90 minutes after ingestion, indicating that significant variability in response can occur.

In a more severe case, a 19-year-old male ingested 8,000 mg of ibuprofen over a few hours. He experienced dizziness but ultimately recovered following parenteral hydration and three days of bed rest.

Management of acute ibuprofen overdosage should be initiated promptly. If the ingestion occurred within the last hour, the stomach should be emptied through vomiting or gastric lavage, as little drug will likely be recovered after this timeframe. The administration of oral activated charcoal may be beneficial in reducing both absorption and reabsorption of ibuprofen. Additionally, due to the drug's acidic nature, administering alkali and inducing diuresis may also be advantageous in facilitating urinary excretion.

Healthcare professionals are advised to monitor patients closely for symptoms and to implement supportive care as necessary.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy has been associated with teratogenic effects, particularly when administered around 20 weeks gestation or later. Specifically, there is an increased risk of premature closure of the fetal ductus arteriosus and potential fetal renal dysfunction, which may lead to oligohydramnios and, in some instances, neonatal renal impairment. Oligohydramnios, while often reversible upon discontinuation of treatment, can result in complications such as limb contractures and delayed lung maturation if prolonged.

In cases where NSAID treatment is deemed necessary between approximately 20 and 30 weeks of gestation, it is advised to limit the use of ibuprofen tablets to the lowest effective dose for the shortest duration possible. Ultrasound monitoring of amniotic fluid is recommended if treatment extends beyond 48 hours, and ibuprofen tablets should be discontinued if oligohydramnios is detected, with follow-up conducted according to established clinical practices.

Data from observational studies regarding other potential embryo-fetal risks associated with NSAID use during the first or second trimesters of pregnancy remain inconclusive. Animal reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, it is important to note that findings from animal studies are not always predictive of human outcomes.

Animal pharmacology and toxicology data indicate that prostaglandins play a critical role in endometrial vascular permeability, blastocyst implantation, and decidualization. In studies involving animal models, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has been linked to increased pre- and post-implantation loss. Additionally, prostaglandins are essential for fetal kidney development, and published animal studies have reported that prostaglandin synthesis inhibitors can impair kidney development when administered at clinically relevant doses.

Postmarketing Experience

During postapproval use of ibuprofen, the following adverse reactions have been identified through voluntary reports and surveillance programs: exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE). These events were reported in the context of pharmacovigilance and are included for informational purposes.

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as ibuprofen, and periodically throughout the course of treatment. It is important for patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients 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. Patients should be made aware that ibuprofen, like other NSAIDs, may cause serious cardiovascular side effects, such as myocardial infarction or stroke, which could lead to hospitalization or even death. Although serious cardiovascular events can occur without warning, patients should be alert for signs and symptoms and seek medical advice if they observe any indicative signs.

Patients should also be apprised of the potential gastrointestinal discomfort associated with ibuprofen tablets, as well as the risk of serious gastrointestinal side effects, such as ulcers and bleeding, which may result in hospitalization or death. Serious gastrointestinal complications can occur without warning symptoms; therefore, patients should be instructed to be alert for signs of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and to seek medical advice if they experience any of these symptoms.

Patients should be advised to discontinue ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible. Additionally, patients should be informed about the symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and should be instructed to contact their healthcare provider if such symptoms occur.

It is crucial for patients to be aware of 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 occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should also be informed about the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat, and should be instructed to seek immediate emergency help if these symptoms arise.

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

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), in accordance with USP Controlled Room Temperature guidelines. Care should be taken to avoid exposure to excessive heat, specifically temperatures exceeding 40ºC (104ºF). Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Borderline elevations of liver tests may occur in up to 15% of patients taking non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets. Notable elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST), approximately three or more times the upper limit of normal, have been reported in about 1% of patients in clinical trials. Clinicians should monitor hemoglobin or hematocrit levels in patients on long-term NSAID therapy, including ibuprofen, if they exhibit any signs or symptoms of anemia.

Patients should be counseled on the importance of being aware of potential cardiovascular thrombotic events, such as chest pain, shortness of breath, weakness, or slurring of speech, and should report any such symptoms to their healthcare provider immediately. They are also encouraged to read the NSAID Medication Guide that accompanies each prescription. In postmarketing studies, a decrease in hemoglobin of 1 gram or more was observed in 17.1% of patients taking 1,600 mg of ibuprofen daily for osteoarthritis and in 22.8% of those taking 2,400 mg daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were noted in these studies.

FDA Insert (PDF)

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

View full prescribing information (PDF)