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 74-77° C. It is very slightly soluble in water (<1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone. The tablets are available in strengths of 400 mg, 600 mg, and 800 mg 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 associated with rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in pediatric populations have not been conducted. Therefore, healthcare professionals should exercise caution when considering the use of ibuprofen in children.

Dosage and Administration

Healthcare professionals should carefully consider the potential benefits and risks of ibuprofen tablets and other treatment options before initiating therapy. It is recommended to use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

After assessing the response to initial therapy with ibuprofen tablets, the dose and frequency should be adjusted to meet the specific needs of each patient. The total daily dose should not exceed 3200 mg. In cases where gastrointestinal complaints arise, ibuprofen tablets should be administered with meals or milk to mitigate these effects.

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 three to four times a day. The dosage should be tailored to each patient, with adjustments made based on the severity of symptoms at the initiation of therapy or in response to treatment.

It is noted that patients with rheumatoid arthritis may require higher doses of ibuprofen tablets compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should always be employed.

For the treatment of mild to moderate pain, a dosage of 400 mg may be administered every 4 to 6 hours as necessary for pain relief. In the case of dysmenorrhea, ibuprofen tablets should be given at the onset of pain, starting with a dose of 400 mg every 4 hours as needed for relief.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. They should not be administered to individuals who have experienced 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, ibuprofen tablets are contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Caution is advised when considering ibuprofen for patients with preexisting asthma, and it should not be given to those with aspirin-sensitive asthma. If a patient experiences blurred vision, diminished vision, scotomata, or changes in color vision while taking ibuprofen, the medication should be discontinued, and an ophthalmologic examination is recommended.

Warnings and Precautions

Non-steroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen Tablets, are associated with an increased risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is likely to escalate with prolonged use. Ibuprofen Tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

Patients with a history of cardiovascular disease or risk factors are at a heightened risk for serious cardiovascular thrombotic events. Therefore, the use of Ibuprofen Tablets should be avoided in individuals with a recent myocardial infarction unless the anticipated benefits outweigh the risks of recurrent cardiovascular events. Continuous monitoring for signs of cardiac ischemia is recommended in these patients.

NSAIDs also pose a significant risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can occur without warning and at any time during treatment. Elderly patients are particularly vulnerable to these serious gastrointestinal complications. Physicians should monitor patients on long-term NSAID therapy for signs or symptoms of gastrointestinal bleeding.

The initiation of NSAID treatment may lead to new hypertension or exacerbate preexisting hypertension. Blood pressure should be closely monitored during the initiation and throughout the course of NSAID therapy. Additionally, the use of Ibuprofen Tablets in patients with severe heart failure should be approached with caution, as the benefits must outweigh the risks of worsening heart failure. Patients should be monitored for signs of heart failure deterioration.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can occur unexpectedly. Discontinuation of Ibuprofen Tablets is warranted at the first sign of a skin rash or any indication of hypersensitivity. Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen; emergency medical assistance should be sought immediately in such cases.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs. If any signs or symptoms indicative of DRESS arise, Ibuprofen Tablets should be discontinued, and the patient should be evaluated promptly. Furthermore, the use of NSAIDs in pregnant women at approximately 30 weeks gestation and later is contraindicated due to the risk of premature closure of the fetal ductus arteriosus.

Ibuprofen Tablets are not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Patients on long-term corticosteroid therapy should have their medication tapered gradually if discontinuation is necessary. For patients on long-term NSAID treatment, hemoglobin or hematocrit levels should be monitored if any signs or symptoms of anemia are present. Additionally, those who may be adversely affected by changes in platelet function should be closely observed.

Regular laboratory tests are recommended for patients on long-term NSAID therapy. A complete blood count (CBC) and chemistry profile should be checked periodically. If clinical signs or symptoms consistent with liver or renal disease develop, or if abnormal liver tests persist or worsen, Ibuprofen Tablets should be discontinued.

In cases of anaphylactoid reactions, immediate emergency medical help is essential. Patients should also discontinue Ibuprofen Tablets and contact their healthcare provider if they experience clinical signs or symptoms indicative of liver disease, systemic manifestations such as eosinophilia or rash, or if oligohydramnios occurs, following appropriate clinical guidelines.

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. These events may occur early in treatment and the risk may increase with prolonged use. Additionally, serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, can also be fatal and may occur at any time during treatment without warning symptoms. Elderly patients are particularly at greater risk for these gastrointestinal complications. Renal effects, such as acute renal failure and renal papillary necrosis, have been associated with long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs). Anaphylactoid reactions may occur in patients without prior exposure to the medication, and serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported and can be fatal. Furthermore, the use of NSAIDs may lead to fetal toxicity, including premature closure of the fetal ductus arteriosus and renal dysfunction.

Common adverse reactions reported by patients 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 some patients experiencing depression, insomnia, and confusion. Dermatologic reactions can include rash, pruritus, and in some cases, more severe conditions such as vesiculobullous eruptions and urticaria. Hematologic reactions may involve neutropenia, agranulocytosis, and thrombocytopenia, while metabolic and endocrine effects can include decreased appetite and gynecomastia.

Additional adverse reactions noted in clinical trials and postmarketing experiences include dry eyes and mouth, gingival ulcer, and rhinitis. Rare occurrences of aseptic meningitis with fever and coma have also been documented. Patients have reported visual disturbances, such as blurred vision and changes in color vision.

It is essential for healthcare providers to monitor patients for these adverse reactions and to weigh the benefits of treatment against the potential risks.

Drug Interactions

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and various medications may lead to significant drug interactions that require careful consideration.

Antihypertensive Agents NSAIDs may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors when administered 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 taken prior to aspirin. This interaction may increase the risk of cardiovascular events; therefore, alternative analgesics should be considered for patients on low-dose aspirin therapy.

Diuretics The use of ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics. Close observation for renal failure is recommended during concomitant therapy.

Lithium Ibuprofen has been shown to elevate plasma lithium levels and reduce renal clearance of lithium, which increases the risk of lithium toxicity. Monitoring of lithium levels is advised when these medications are used together.

Methotrexate NSAIDs may enhance the toxicity of methotrexate. Caution is warranted when these agents are used concomitantly, and patients should be monitored for signs of toxicity.

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

Gastrointestinal Agents Co-administration of cimetidine or ranitidine with ibuprofen does not appear to 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). 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 tablets, during pregnancy is associated with significant risks, particularly when used after approximately 20 weeks of gestation. The administration of NSAIDs at this stage has been linked to fetal renal dysfunction, which can lead to oligohydramnios and, in some cases, neonatal renal impairment. The risk of these adverse outcomes increases with use at around 30 weeks of gestation or later, where there is a heightened risk of premature closure of the fetal ductus arteriosus.

Data from observational studies regarding the potential risks of NSAID use during the first and second trimesters remain inconclusive. 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%. While animal studies have not demonstrated developmental abnormalities associated with ibuprofen, these findings may not be predictive of human outcomes, and there are no adequate and well-controlled studies in pregnant women. Therefore, ibuprofen should only be used during pregnancy if the potential benefits outweigh the risks to the fetus.

Animal data suggest that prostaglandins play a crucial role in various reproductive processes, including endometrial vascular permeability and fetal kidney development. Inhibition of prostaglandin synthesis by NSAIDs like ibuprofen has been shown to increase pre- and post-implantation loss and may impair kidney development at clinically relevant doses.

If NSAID use is deemed necessary after 20 weeks of gestation, it is recommended to limit the dosage to the lowest effective amount for the shortest duration possible. Should treatment with ibuprofen tablets extend beyond 48 hours, monitoring for oligohydramnios via ultrasound is advised. In cases where oligohydramnios is detected, discontinuation of ibuprofen tablets should be considered, followed by appropriate clinical follow-up.

Published literature indicates that the adverse effects associated with maternal NSAID use, particularly after 20 weeks of gestation, may manifest after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours post-initiation. While many instances of decreased amniotic fluid have been transient and reversible upon cessation of the drug, there are limited case reports of irreversible neonatal renal dysfunction, some requiring invasive interventions such as exchange transfusion or dialysis.

It is important to note that methodological limitations in postmarketing studies, including the absence of control groups and insufficient data on dosage, duration, and timing of exposure, hinder the ability to establish a reliable risk estimate for adverse fetal and neonatal outcomes associated with maternal NSAID use. Additionally, the majority of safety data concerning neonatal outcomes have involved preterm infants, raising questions about the applicability of these findings to full-term infants exposed to NSAIDs through maternal use.

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; therefore, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, subsequently, renal blood flow. This can precipitate overt renal decompensation, particularly in patients at greatest risk, including 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. However, there is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease, and 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 may occur after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after NSAID initiation. If NSAID treatment is required between approximately 20 weeks and 30 weeks gestation, it is recommended to limit 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 critical 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 oxygen supplementation and intravenous fluids. Blood analysis approximately 8½ hours post-ingestion revealed a concentration of 102.9 mcg/mL.

Conversely, two separate cases involving children weighing around 10 kg who ingested approximately 120 mg/kg of ibuprofen showed no acute signs of intoxication. Notably, one of these children had a blood level of 700 mcg/mL measured 90 minutes after ingestion, indicating that significant variability in response can occur.

In an adult case, a 19-year-old male ingested 8,000 mg of ibuprofen over several hours. He experienced dizziness but ultimately recovered following parenteral hydration and three days of bed rest, highlighting the importance of supportive care in managing overdose situations.

For the management of acute ibuprofen overdosage, it is critical to empty the stomach through vomiting or gastric lavage within one hour of ingestion, as little drug will likely be recovered after this period. The administration of alkali and the induction of diuresis may be beneficial due to the acidic nature of ibuprofen and its urinary excretion. Additionally, oral activated charcoal can be utilized to reduce further absorption of the drug.

Supportive measures are paramount in the management of ibuprofen overdose. Continuous monitoring for signs of toxicity is essential, and healthcare professionals should provide appropriate care based on the clinical presentation of the patient.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy, particularly from approximately 20 weeks gestation onward, has been associated with an increased risk of fetal renal dysfunction, leading to oligohydramnios, and in some instances, neonatal renal impairment. Additionally, administration of NSAIDs around 30 weeks gestation or later may elevate the risk of premature closure of the fetal ductus arteriosus. Observational studies regarding other potential embryo-fetal risks associated with NSAID use during the first or second trimesters have yielded inconclusive results.

In animal reproductive studies conducted in rats and rabbits, no evidence of developmental abnormalities was observed. However, it is important to note that animal reproduction studies do not always predict human responses. Oligohydramnios, which may occur as a result of fetal renal dysfunction, is often reversible upon discontinuation of treatment; however, complications from prolonged oligohydramnios can include limb contractures and delayed lung maturation. In certain postmarketing cases of impaired neonatal renal function, invasive interventions such as exchange transfusion or dialysis were necessary.

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 linked to increased pre- and post-implantation loss. Furthermore, 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 effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown.

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 of DRESS have resulted in fatal or life-threatening outcomes. The condition typically presents with symptoms such as fever, rash, lymphadenopathy, and/or facial swelling, although it may also manifest with hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Symptoms may mimic those of an acute viral infection, and eosinophilia is frequently observed. Due to the variable presentation of DRESS, involvement of other organ systems may occur. Early signs of hypersensitivity, including fever or lymphadenopathy, may be present even in the absence of a rash. In such instances, it is advised to discontinue ibuprofen tablets and conduct an immediate evaluation of the patient.

Additionally, findings from two postmarketing clinical studies indicated a higher incidence of decreased hemoglobin levels than previously reported. A decrease in hemoglobin of 1 gram or more was observed in 17.1% of 193 patients receiving 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients taking 2400 mg daily for rheumatoid arthritis. Positive stool occult blood tests and elevated serum creatinine levels were also noted in these studies.

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 to encourage 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, which may include chest pain, shortness of breath, weakness, or slurring of speech. Patients should be instructed to report any of these symptoms to their healthcare provider immediately. It is crucial to communicate that ibuprofen tablets, like other NSAIDs, may lead to serious cardiovascular side effects, such as myocardial infarction or stroke, which could result in hospitalization or even death. Although serious cardiovascular events can occur without warning, patients should remain alert for the aforementioned signs and symptoms and seek medical advice if they observe any indicative signs.

Patients should also be made aware of the potential gastrointestinal discomfort associated with ibuprofen tablets, as well as the risk of serious gastrointestinal side effects, including ulcers and bleeding, which may also lead to hospitalization or death. Serious gastrointestinal complications can occur without warning symptoms; therefore, patients should be vigilant for signs of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they experience any of these symptoms. The importance of follow-up in these cases should be emphasized.

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, they should be alert for symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and should contact their healthcare provider if such symptoms occur.

It is essential to inform patients 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 informed 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.

For pregnant women, it is important to advise against 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 accordance with the following specifications. It should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), in compliance 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

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as there is a risk of serious GI tract ulcerations and bleeding associated with the use of NSAIDs. For patients undergoing long-term treatment with NSAIDs, it is recommended that complete blood counts (CBC) and chemistry profiles be checked periodically to assess for potential adverse effects.

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

FDA Insert (PDF)

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

View full prescribing information (PDF)