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° 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 tablets are available in 800 mg tablets for oral administration. The inactive ingredients include colloidal silicon dioxide, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, talc, magnesium stearate, and Opadry II, which contains hypromellose, polyethylene glycol, sodium citrate, lactose monohydrate, 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. The total daily dose must not exceed 3200 mg. In cases where gastrointestinal complaints arise, ibuprofen tablets should be administered with meals or milk to mitigate discomfort.

For the management of rheumatoid arthritis and osteoarthritis, the suggested dosage ranges from 1200 mg to 3200 mg daily, which can be divided into doses of 400 mg, 600 mg, or 800 mg taken three to four times a day (tid or qid). It is important to note that some patients may experience better outcomes with a total daily dose of 3200 mg compared to 2400 mg.

Dose adjustments should be made based on the patient's response to initial therapy. The dosage and frequency must be tailored to meet individual patient needs, with the possibility of lowering or raising the dose depending on the severity of symptoms.

For the relief of mild to moderate pain, a dose of 400 mg may be administered every 4 to 6 hours as needed. Clinical trials have indicated that doses exceeding 400 mg do not provide greater efficacy than the 400 mg dose.

In the case of dysmenorrhea, ibuprofen tablets should be given at a dose of 400 mg every 4 hours as necessary for pain relief.

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, urticaria, 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 risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, has been associated with the use of ibuprofen tablets. These events can be fatal and may occur early in treatment, with the risk potentially increasing with the duration of use. It is advised to avoid the use of ibuprofen in patients with a recent MI unless the benefits outweigh the risks. Healthcare professionals should monitor patients for signs of cardiac ischemia. Additionally, NSAIDs may lead to new hypertension or exacerbate pre-existing hypertension; therefore, blood pressure should be monitored closely. The use of ibuprofen is also contraindicated in patients with severe heart failure unless the benefits outweigh the risks, and signs of worsening heart failure should be monitored.

NSAIDs, including ibuprofen, can cause serious gastrointestinal adverse events such as inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, which can be fatal. These events may occur at any time, with or without warning symptoms. Patients with a history of peptic ulcer disease or gastrointestinal bleeding are at more than a tenfold increased risk for developing a GI bleed. To minimize this risk, it is recommended to use the lowest effective dose for the shortest duration possible and to remain vigilant for signs and symptoms of gastrointestinal ulcerations and bleeding.

Long-term administration of NSAIDs can result in renal injury, particularly in patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. The use of ibuprofen is not recommended in patients with advanced renal disease; if treatment is deemed necessary, close monitoring of renal function is advised.

Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen. In the event of such a reaction, emergency medical assistance should be sought immediately.

Serious skin adverse reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported. Discontinuation of ibuprofen should occur at the first appearance of a skin rash or any sign of hypersensitivity.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has also been reported in patients taking NSAIDs. If signs or symptoms such as fever or lymphadenopathy are present, ibuprofen should be discontinued, and the patient should be evaluated immediately.

In pregnant women, the use of NSAIDs should be avoided around 30 weeks of gestation and later due to the risk of premature closure of the fetal ductus arteriosus. Additionally, the use of NSAIDs around 20 weeks of gestation or later may lead to fetal renal dysfunction, resulting in oligohydramnios and neonatal renal impairment. If oligohydramnios occurs, ibuprofen should be discontinued.

Healthcare professionals should instruct patients to seek emergency medical help if an anaphylactoid reaction occurs. Furthermore, patients should be advised to stop taking ibuprofen and contact their healthcare provider if they experience signs of serious cardiovascular events, gastrointestinal bleeding, serious skin reactions, or symptoms indicative of DRESS.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication, categorized by seriousness and frequency.

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 events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal complications can occur at any time during treatment and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Other serious adverse reactions reported include anaphylaxis, serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), all of which can be life-threatening. Patients may also experience drug reaction with eosinophilia and systemic symptoms (DRESS), which has been reported as potentially fatal.

Common adverse reactions observed in clinical trials and postmarketing experiences encompass a variety of systems:

Gastrointestinal: Nausea, epigastric pain, heartburn, diarrhea, abdominal distress, and constipation are frequently reported. More severe gastrointestinal issues such as gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis have also been noted.

Central Nervous System: Patients may report dizziness, headache, nervousness, depression, insomnia, confusion, emotional liability, somnolence, and paresthesias. Rarely, severe reactions such as aseptic meningitis with fever and coma, hallucinations, dream abnormalities, and pseudotumor cerebri have been documented.

Dermatologic: Reactions may include rash (including maculopapular types), pruritus, vesiculobullous eruptions, urticaria, erythema multiforme, alopecia, and photoallergic skin reactions.

Special Senses: Adverse effects may involve tinnitus, hearing loss, amblyopia, conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic: Patients may experience neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia, eosinophilia, and bleeding episodes.

Metabolic/Endocrine: Common reactions include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

Cardiovascular: Patients may experience edema, fluid retention, congestive heart failure (especially in those with marginal cardiac function), elevated blood pressure, palpitations, and arrhythmias.

Allergic: Reactions may include abdominal pain, fever, chills, nausea, vomiting, bronchospasm, serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal: Adverse reactions may involve acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria, and renal papillary necrosis.

Miscellaneous: Patients may report dry eyes and mouth, gingival ulcer, and rhinitis.

It is important to note that patients with asthma may have aspirin-sensitive asthma and should not be administered ibuprofen tablets.

Drug Interactions

Concomitant use of non-steroidal 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 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 before aspirin. To mitigate this interaction, it is recommended that immediate-release low-dose aspirin be taken at least 2 hours prior to ibuprofen. Due to the potential for increased adverse effects, concomitant administration of ibuprofen and aspirin is generally not recommended.

Diuretics Ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics. Patients should be closely observed for signs of renal failure when these medications are used together.

Lithium The use of ibuprofen can elevate plasma lithium levels and reduce renal clearance of lithium, thereby increasing the risk of lithium toxicity. Monitoring of lithium levels is recommended in patients receiving this combination.

Methotrexate Caution is advised when administering NSAIDs with methotrexate, as there is a potential for enhanced toxicity of methotrexate. Close monitoring of patients is warranted.

Anticoagulants The risk of bleeding is increased when ibuprofen is used in conjunction with warfarin-type anticoagulants. Caution should be exercised in patients on this combination, and appropriate monitoring for signs of bleeding 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 and adolescents.

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 significant risks, particularly when used after approximately 20 weeks of gestation. The administration of NSAIDs at around 30 weeks of gestation or later can lead to premature closure of the fetal ductus arteriosus, which may result in serious fetal complications. Additionally, NSAID use during this period has been linked to fetal renal dysfunction, leading to oligohydramnios and, in some cases, neonatal renal impairment.

Due to these risks, it is recommended that the use of ibuprofen tablets be limited to the lowest effective dose and shortest duration possible if necessary after 20 weeks of gestation. Furthermore, ibuprofen tablets should be avoided entirely after 30 weeks of gestation. If treatment with ibuprofen extends beyond 48 hours, healthcare providers should consider monitoring the pregnancy with ultrasound for signs of oligohydramnios. Should oligohydramnios be detected, discontinuation of ibuprofen tablets is advised, followed by appropriate clinical follow-up.

While reproductive studies in rats and rabbits have not shown evidence of developmental abnormalities, the predictive value of animal studies for human outcomes is limited. Prostaglandins play a crucial role in various aspects of pregnancy, including endometrial vascular permeability and fetal kidney development. Animal studies have indicated that the use of prostaglandin synthesis inhibitors like ibuprofen can impair kidney development and increase the risk of pre- and post-implantation loss.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2-4% and 15-20%, respectively. However, the specific background risk associated with ibuprofen tablets remains unknown. There are no adequate, well-controlled studies in pregnant women, and ibuprofen should only be used during pregnancy if the potential benefits outweigh the risks to the fetus.

Published literature indicates that adverse outcomes related to maternal NSAID use, such as fetal renal dysfunction and oligohydramnios, may occur after days to weeks of treatment, although some cases of oligohydramnios have 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 have been limited case reports of irreversible neonatal renal dysfunction requiring invasive interventions.

Given the methodological limitations of existing studies, including the lack of control groups and insufficient data on dosage and timing, a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use cannot be established. Additionally, the effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown. Therefore, healthcare professionals should exercise caution and consider these factors when prescribing ibuprofen tablets to pregnant patients.

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. Renal toxicity may occur in patients where renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs can lead to a dose-dependent reduction in prostaglandin formation, which may subsequently decrease renal blood flow and precipitate overt renal decompensation.

Patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly are at the greatest risk for these adverse reactions. 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.

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 instances, neonatal renal impairment. Oligohydramnios may be reversible upon discontinuation of treatment. If NSAID treatment is deemed necessary between 20 and 30 weeks of gestation, it is recommended 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 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 compensatory 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 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. Therefore, careful monitoring of renal function is recommended in patients with hepatic impairment who are prescribed NSAIDs. Should any signs of renal toxicity arise, discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state. Adjustments to dosage or alternative therapeutic strategies may be necessary based on the patient's overall clinical status and liver function.

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 consumed 8,000 mg of ibuprofen over several hours. He experienced dizziness but ultimately recovered following parenteral hydration and bed rest, highlighting the importance of supportive care in managing ibuprofen overdose.

For the management of acute overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage within one hour of ingestion, as little drug is likely to 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 critical 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, during pregnancy has been associated with teratogenic effects. Specifically, administration of NSAIDs around 30 weeks gestation or later increases the risk of premature closure of the fetal ductus arteriosus. Additionally, the use of these medications from approximately 20 weeks gestation onward 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.

Oligohydramnios, a condition that may arise from the use of NSAIDs, 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 have been necessary.

Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities. Nonetheless, it is important to note that animal reproduction studies do not always predict human responses. Data from observational studies regarding other potential embryofetal risks associated with NSAID use during the first or second trimesters of pregnancy remain inconclusive.

Postmarketing Experience

During postapproval use of ibuprofen, several adverse reactions have been identified. These reactions have been reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Among the reported adverse reactions, skin and appendage-related events include exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as ibuprofen tablets, 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 tablets, 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. Although serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should seek medical advice upon observing any indicative signs or symptoms and understand the importance of follow-up.

Additionally, patients should be informed that ibuprofen tablets can cause serious skin side effects, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may also result in hospitalization or death. Patients should be alert for signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity, such as itching, and should seek medical advice if they observe any indicative signs or symptoms. They should be advised to stop taking ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

Patients should also be advised to be alert for symptoms of congestive heart failure, including 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 symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

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

Pregnant women should be informed 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 advised that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

Finally, healthcare providers should monitor patients for signs or symptoms of gastrointestinal bleeding, as serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms. Patients on long-term treatment with NSAIDs should have their complete blood count (CBC) and chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash), or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued.

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 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, may experience borderline elevations in liver tests, occurring in up to 15% of cases. Notable elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) have been reported in approximately 1% of patients in clinical trials. Long-term NSAID users should have their hemoglobin or hematocrit monitored if they show signs of anemia. Additionally, postmarketing studies have indicated occurrences of positive stool occult blood tests and elevated serum creatinine levels.

Clinicians should counsel patients on the potential risks associated with NSAID therapy, advising them to read the accompanying NSAID Medication Guide. Patients should be vigilant for symptoms indicative of cardiovascular thrombotic events, such as chest pain, shortness of breath, weakness, or slurred speech, and report these symptoms to their healthcare provider immediately. Furthermore, postmarketing clinical studies have revealed a higher incidence of decreased hemoglobin levels than previously documented, with significant decreases observed in a notable percentage of patients on high doses of ibuprofen for osteoarthritis and rheumatoid arthritis. Rare cases of aseptic meningitis with fever and coma have also been reported in patients undergoing ibuprofen therapy.

FDA Insert (PDF)

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

View full prescribing information (PDF)