Ibuprofen

Description

Ibuprofen tablets contain the active ingredient ibuprofen, which is (±)-2-(p-isobutylphenyl) propionic acid. Ibuprofen is a white powder with a melting point of 74-77° 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. 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

The lowest effective dose should be utilized for the shortest duration consistent with individual patient treatment goals. After assessing the response to initial therapy, healthcare professionals should adjust the dose and frequency to meet the specific needs of each patient. The total daily dose must not exceed 3200 mg. In cases where gastrointestinal complaints arise, it is recommended to administer the medication with meals or milk.

For the management of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage ranges from 1200 mg to 3200 mg daily. This can be achieved through various dosing regimens, such as 300 mg four times a day or 400 mg, 600 mg, or 800 mg administered three to four times a day. The dosage should be individualized and may be adjusted based on the severity of symptoms, with patients suffering from rheumatoid arthritis potentially requiring higher doses than those with osteoarthritis.

For the treatment of mild to moderate pain, a dosage of 400 mg may be administered every 4 to 6 hours as needed for pain relief. In the case of dysmenorrhea, a dosage of 400 mg every 4 hours may be given as necessary to alleviate pain.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, they should not be administered to individuals who have a history of asthma, urticarial, 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. Furthermore, the use of ibuprofen tablets is contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Caution is advised when considering ibuprofen for patients with preexisting asthma, particularly those with aspirin-sensitive asthma, due to the potential for exacerbation of respiratory conditions.

Warnings and Precautions

Increased cardiovascular risks are associated with the use of this medication, 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 the treatment course and may escalate with prolonged use. The medication is contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

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

Anaphylactoid reactions may occur in patients who have not previously been exposed to the medication. In such cases, it is imperative to seek emergency medical assistance immediately. Additionally, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can occur unexpectedly. The medication should be discontinued at the first sign of a skin rash or any indication of hypersensitivity.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is another potential adverse reaction that can be fatal or life-threatening. If any signs or symptoms of DRESS are observed, ibuprofen tablets should be discontinued, and the patient should be evaluated without delay.

For patients on prolonged corticosteroid therapy, it is essential to taper the corticosteroids slowly if discontinuation is deemed necessary. Patients exhibiting symptoms or signs indicative of liver dysfunction should be assessed for severe hepatic reactions while on therapy, and the medication should be discontinued if clinical signs of liver disease develop. Long-term treatment patients should have their hemoglobin or hematocrit levels monitored, particularly if they show signs of anemia, and those who may be adversely affected by changes in platelet function should be closely observed.

Monitoring for signs or symptoms of gastrointestinal bleeding is recommended for patients on long-term NSAID treatment. Additionally, periodic checks of complete blood count (CBC) and chemistry profiles are advised for patients undergoing long-term treatment. Ibuprofen tablets should be discontinued if clinical signs of liver or renal disease arise or if abnormal liver tests persist or worsen.

Emergency medical help should be sought in the event of an anaphylactoid reaction. Patients should discontinue ibuprofen tablets at the first appearance of a skin rash or any other sign of hypersensitivity. If signs or symptoms of meningitis develop, the possibility of a connection to ibuprofen tablets should be considered, and use should be discontinued.

Side Effects

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

Serious adverse reactions include cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may arise early in treatment and is known to increase with prolonged use. Additionally, serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, can occur at any time during therapy, often without warning symptoms. Elderly patients are particularly at heightened risk for these gastrointestinal complications. Renal effects, such as acute renal failure and renal papillary necrosis, have also been reported, especially with long-term administration.

Skin reactions can be severe, with reports of exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, all of which may be fatal. Anaphylactoid reactions have been noted in patients without prior exposure to the medication, and patients with the aspirin triad should not receive this treatment. Furthermore, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has been documented, with some cases being life-threatening.

Common adverse reactions include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, and abdominal cramps. Central nervous system effects may manifest as dizziness, headache, and nervousness, with more severe symptoms like depression, insomnia, and confusion occurring in some patients. Dermatologic reactions may include rash, pruritus, and more serious conditions like urticaria and alopecia.

Hematologic reactions such as neutropenia, agranulocytosis, and thrombocytopenia have been observed, alongside metabolic/endocrine effects like decreased appetite and gynecomastia. Cardiovascular issues may present as edema, fluid retention, and arrhythmias. Renal complications can include decreased creatinine clearance and hematuria.

Miscellaneous reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis. Aseptic meningitis with fever and coma has been observed in rare instances, warranting consideration of a potential link to the medication if symptoms develop.

Patients should be monitored closely for these adverse reactions, and any severe or concerning symptoms should prompt immediate medical evaluation.

Drug Interactions

The concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and various other medications can lead to significant drug interactions that may affect therapeutic outcomes and patient safety.

Antihypertensive Agents NSAIDs may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors when used together. It is advisable to monitor blood pressure closely in patients receiving this combination.

Antiplatelet Agents Ibuprofen can interfere with the antiplatelet activity 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.

Diuretics The use of ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics, which could potentially lead to renal failure. Patients should be monitored closely for renal function when these medications are used concurrently.

Lithium Ibuprofen has been shown to elevate plasma lithium levels and reduce renal clearance of lithium, thereby increasing the risk of lithium toxicity. Regular monitoring of lithium levels is recommended for patients taking this combination.

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

Anticoagulants Caution is warranted when administering ibuprofen to patients on warfarin-type anticoagulants due to an increased risk of serious gastrointestinal bleeding. Close monitoring of coagulation parameters is recommended.

Gastrointestinal Agents Co-administration of cimetidine or ranitidine with ibuprofen does not have a substantive effect on 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

The 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 (65 years and older) with this medication, as with any nonsteroidal anti-inflammatory drugs (NSAIDs). The geriatric population may have an increased risk of adverse effects, necessitating careful monitoring and consideration of individual patient factors when determining treatment plans. It is essential for healthcare providers to assess the overall health status and comorbidities of geriatric patients to ensure safe and effective use of the medication.

Pregnancy

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy is associated with potential risks to fetal outcomes. 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 that the use of ibuprofen tablets be limited in dose and duration between approximately 20 and 30 weeks of gestation, and avoided entirely at around 30 weeks of gestation and later in pregnancy.

Observational studies have provided inconclusive data regarding other potential embryo-fetal risks associated with NSAID use during the first and second trimesters. In the general U.S. population, the background rate for major malformations in clinically recognized pregnancies is estimated at 2-4%, with a pregnancy loss rate of 15-20%, regardless of drug exposure. Animal reproductive studies have not demonstrated developmental abnormalities in rats and rabbits; however, these studies may not accurately predict human responses.

There are no adequate and well-controlled studies in pregnant women regarding the use of ibuprofen. Therefore, ibuprofen should only be used during pregnancy if the potential benefits justify the potential risks to the fetus. Administration of prostaglandin synthesis inhibitors, such as ibuprofen, has been linked to increased pre- and post-implantation loss in animal studies. Prostaglandins play a crucial role in fetal kidney development, and their inhibition has been reported to impair kidney development at clinically relevant doses.

If NSAID use is deemed necessary after approximately 20 weeks of gestation, it is advised to limit the treatment to the lowest effective dose for the shortest duration possible. If treatment with ibuprofen tablets extends beyond 48 hours, monitoring with ultrasound for oligohydramnios should be considered. In cases where oligohydramnios is detected, ibuprofen tablets should be discontinued, and follow-up should be conducted according to clinical practice guidelines.

Published literature indicates that the use of NSAIDs 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, oligohydramnios, and, in some instances, neonatal renal impairment. Adverse outcomes may manifest after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours after NSAID initiation. While many cases of decreased amniotic fluid were transient and reversible upon cessation of the drug, there have been limited case reports of neonatal renal dysfunction occurring without oligohydramnios, some of which were irreversible and required invasive treatments such as exchange transfusion or dialysis.

Methodological limitations in postmarketing studies, including the absence of control groups and insufficient information regarding dose, duration, and timing of drug exposure, hinder the establishment of a reliable estimate of the risk of adverse fetal and neonatal outcomes associated with maternal NSAID use. Furthermore, the safety data on neonatal outcomes primarily involve preterm infants, raising concerns about the generalizability of certain reported risks to full-term 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 tablets, lactating mothers should consider the importance of the drug to their health when making a decision to either discontinue breastfeeding 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 may play a compensatory role in maintaining renal perfusion. The use of an NSAID in these individuals can lead to a dose-dependent decrease in prostaglandin formation, which may subsequently reduce renal blood flow and precipitate overt renal decompensation.

Patients at the highest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, those 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 tablets in patients with advanced renal disease; therefore, treatment with ibuprofen tablets is not recommended in this population. If initiation of ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's renal function is advised.

Additionally, the use of NSAIDs, including ibuprofen tablets, during pregnancy, particularly around 20 weeks gestation or later, may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes can occur after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after NSAID initiation. While oligohydramnios is often reversible upon discontinuation of treatment, if NSAID therapy is required between 20 and 30 weeks gestation, it is recommended to limit ibuprofen tablet use 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 conducted according to clinical practice.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when administered 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 critical role in maintaining renal perfusion. In patients with compromised liver function, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate overt renal decompensation.

Patients with hepatic impairment are at an increased risk for renal toxicity, especially those who also have impaired renal function, heart failure, or are taking diuretics and ACE inhibitors. The elderly population may also be particularly vulnerable. It is recommended that healthcare providers closely monitor renal function in these patients during NSAID therapy. Should any signs of renal decompensation occur, discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state. Therefore, careful consideration and monitoring are essential when prescribing NSAIDs to patients with hepatic impairment.

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 oxygen and fluid administration. Blood analysis approximately 8½ hours post-ingestion revealed a concentration of 102.9 mcg/mL.

Conversely, there have been instances where children weighing around 10 kg ingested approximately 120 mg/kg of ibuprofen without exhibiting acute intoxication symptoms. In one such case, a blood level of 700 mcg/mL was recorded 90 minutes after ingestion, indicating that significant variability exists in the response to ibuprofen overdose among pediatric patients.

In an adult case, a 19-year-old male consumed 8,000 mg of ibuprofen over several hours. He experienced dizziness but ultimately recovered following hydration and rest, with no lasting effects reported.

For the management of acute ibuprofen overdosage, it is critical to initiate decontamination measures 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 also be beneficial in reducing both absorption and reabsorption of ibuprofen.

Given the acidic nature of ibuprofen, administering alkali and inducing diuresis may further aid in the elimination of the drug through urinary excretion. Healthcare professionals should remain vigilant in monitoring patients for potential symptoms and complications associated with ibuprofen overdosage, ensuring appropriate supportive care is provided.

Nonclinical Toxicology

Data from observational studies regarding potential embryo-fetal risks associated with NSAID use during the first and second trimesters of pregnancy remain inconclusive. In the general U.S. population, the background rate of major malformations in clinically recognized pregnancies is estimated at 2-4%, with a pregnancy loss rate of 15-20%, irrespective of drug exposure. Animal reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities; however, the predictive value of animal studies for human response is limited. There are no adequate and well-controlled studies in pregnant women, and ibuprofen should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.

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

The use of NSAIDs, including ibuprofen tablets, is advised against in pregnant women at approximately 30 weeks gestation and later due to an increased risk of premature closure of the fetal ductus arteriosus. Furthermore, the use of NSAIDs at around 20 weeks gestation or later may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes typically manifest after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours following the initiation of NSAID therapy. While oligohydramnios is often reversible upon discontinuation of treatment, prolonged cases may lead to complications such as limb contractures and delayed lung maturation. In certain postmarketing cases of impaired neonatal renal function, invasive procedures like exchange transfusion or dialysis were necessary.

If NSAID treatment is deemed necessary between approximately 20 weeks and 30 weeks gestation, it is recommended to limit ibuprofen tablet use to the lowest effective dose for the 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.

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. Renal toxicity has also been observed in patients for whom renal prostaglandins play a compensatory role in maintaining renal perfusion. In such patients, NSAID administration may lead to a dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow, potentially precipitating overt renal decompensation. Patients at highest risk for this reaction include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

No information is available 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 therapy must be initiated, close monitoring of renal function is advised.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of ibuprofen tablets, reported voluntarily or through surveillance programs.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been documented in patients taking NSAIDs, including ibuprofen. Some cases have resulted in fatal or life-threatening outcomes. DRESS typically presents with symptoms such as fever, rash, lymphadenopathy, and/or facial swelling, although other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Symptoms may sometimes mimic those of an acute viral infection, and eosinophilia is frequently observed. Due to the variable presentation of this disorder, involvement of other organ systems may occur. Early signs of hypersensitivity, such as fever or lymphadenopathy, may be present even in the absence of a rash. It is advised that ibuprofen tablets be discontinued and the patient evaluated immediately if such symptoms arise.

In two postmarketing clinical studies, a higher incidence of decreased hemoglobin levels was reported 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 daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were noted in these studies.

Aseptic meningitis, accompanied by fever and coma, has been reported on rare occasions in patients undergoing ibuprofen therapy. While it is more likely to occur in individuals with systemic lupus erythematosus and related connective tissue diseases, cases have also been documented in patients without underlying chronic conditions. If signs or symptoms of meningitis develop in a patient receiving ibuprofen tablets, the potential association with the medication should be considered.

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 the signs and symptoms mentioned and understand the importance of seeking medical advice when they observe any indicative signs.

Additionally, patients should be informed that ibuprofen can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, such as ulcers and bleeding, which may also result in hospitalization or death. Patients should be vigilant for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they experience any of these symptoms. The importance of follow-up in this regard should be emphasized.

Patients should be advised to discontinue ibuprofen immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible. They should also be alert for symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms occur.

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

Patients should also be made aware of 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 informed to avoid the use of ibuprofen and other NSAIDs starting at 30 weeks of gestation due to the risk of premature closure of the fetal ductus arteriosus. If treatment with ibuprofen is necessary for a pregnant woman between approximately 20 to 30 weeks of 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 various package configurations, with specific NDC numbers available for identification. 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

Physicians are advised to monitor patients on long-term treatment with NSAIDs for any signs or symptoms indicative of gastrointestinal bleeding. Additionally, it is recommended that these patients undergo periodic evaluations of their complete blood count (CBC) and chemistry profile to ensure ongoing safety and efficacy of the treatment.

In cases where patients exhibit clinical signs and symptoms suggestive of liver or renal disease, or if systemic manifestations such as eosinophilia or rash occur, ibuprofen tablets should be discontinued. Furthermore, if abnormal liver tests persist or worsen, immediate cessation of the medication is warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)