Ibuprofen

Description

Ibuprofen Tablets, USP contain the active ingredient Ibuprofen, USP, which is (±) -2 - (p-isobutylphenyl) propionic acid. Ibuprofen appears as a white powder with a melting point of 74° C to 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 include inactive ingredients such as carnauba wax, colloidal silicon dioxide, croscarmellose sodium, microcrystalline cellulose, polysorbate 80, povidone, pregelatinized starch, sodium starch glycolate, stearic acid, hypromellose, polyethylene glycol, and propylene glycol. Ibuprofen is available in tablet strengths of 400 mg, 600 mg, and 800 mg for oral administration.

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

Healthcare professionals should carefully evaluate the potential benefits and risks associated with Ibuprofen tablets, considering alternative treatment options before initiating therapy. It is recommended to use the lowest effective dose for the shortest duration that aligns with individual patient treatment goals.

Following the initial therapy with Ibuprofen tablets, the dose and frequency should be tailored to meet the specific needs of the patient. The total daily dose should not exceed 3,200 mg. In cases where gastrointestinal complaints arise, it is advisable to administer Ibuprofen tablets 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 1,200 mg to 3,200 mg daily, which can be administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). The smallest effective dose that provides acceptable control should be utilized.

In the treatment of mild to moderate pain, Ibuprofen tablets may be given at a dosage of 400 mg every 4 to 6 hours as needed for pain relief.

For dysmenorrhea, treatment should commence at the earliest onset of pain, with Ibuprofen tablets administered at a dose of 400 mg every 4 hours as necessary for effective pain relief.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of ibuprofen tablets 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 and stroke, has been associated with the use of Ibuprofen. This risk may manifest early in treatment and is likely to escalate with prolonged use. It is crucial to note that Ibuprofen is contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen, carries the potential for serious gastrointestinal (GI) adverse events. These may include inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. Such events can occur at any time during treatment and may arise without warning symptoms. Therefore, healthcare professionals should remain vigilant for signs or symptoms of GI bleeding.

Anaphylactoid reactions may occur in patients who have not previously been exposed to Ibuprofen. In the event of such a reaction, immediate emergency medical assistance should be sought. Additionally, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, may occur without prior warning. Patients should be advised to discontinue Ibuprofen at the first sign of a skin rash or any other indication of hypersensitivity. If symptoms consistent with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) are observed, Ibuprofen should be discontinued, and the patient should be evaluated promptly.

Ibuprofen is not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of the underlying disease. Furthermore, the pharmacological effects of Ibuprofen in reducing fever and inflammation may obscure the clinical signs necessary for detecting complications in presumed noninfectious, painful conditions.

For patients on long-term NSAID therapy, it is recommended that physicians periodically monitor complete blood count (CBC) and chemistry profiles. If any clinical signs or symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, Ibuprofen should be discontinued. Regular monitoring for GI bleeding is also advised to ensure patient safety.

Side Effects

Adverse reactions associated with the use of this medication have been observed across various systems, with some reactions categorized by their incidence and seriousness.

Gastrointestinal adverse reactions occurring in more than 1% but less than 3% of patients include nausea, epigastric pain, heartburn, diarrhea, abdominal distress, vomiting, indigestion, constipation, abdominal cramps or pain, and fullness of the gastrointestinal tract (bloating and flatulence). Serious gastrointestinal events, although with a precise incidence unknown but estimated to be less than 1%, may include gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage (melena), gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis.

Central nervous system reactions reported in more than 1% but less than 3% of participants include dizziness, headache, and nervousness. Serious reactions with a probable causal relationship, but with a precise incidence unknown, include depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Other central nervous system effects, such as paresthesias, hallucinations, dream abnormalities, and pseudotumor cerebri, have been reported, but their causal relationship remains uncertain.

Dermatologic reactions occurring in more than 1% but less than 3% of patients include rash (including maculopapular types) and pruritus. Serious skin reactions with a probable causal relationship, but with a precise incidence unknown, may include vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia. Additionally, toxic epidermal necrolysis and photoallergic skin reactions have been reported, although their causal relationship is uncertain.

In the realm of special senses, tinnitus has been reported with a probable causal relationship, while other effects such as hearing loss, amblyopia, conjunctivitis, diplopia, optic neuritis, and cataracts have been noted, but their causal relationships remain uncertain.

Hematologic adverse reactions with a probable causal relationship, but with a precise incidence unknown, include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, and decreases in hemoglobin and hematocrit. Bleeding episodes, such as epistaxis and menorrhagia, have also been reported, but their causal relationship is uncertain.

Metabolic and endocrine reactions, including gynecomastia, hypoglycemic reactions, acidosis, and decreased appetite, have been reported, but their causal relationships remain uncertain.

Cardiovascular reactions with a probable causal relationship, but with a precise incidence unknown, include congestive heart failure in patients with marginal cardiac function, elevated blood pressure, and palpitations. Other cardiovascular events, such as arrhythmias (sinus tachycardia and sinus bradycardia), edema, and fluid retention, have been noted, but their causal relationships are uncertain.

Allergic reactions with a probable causal relationship, but with a precise incidence unknown, include a syndrome characterized by abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Other allergic reactions, such as serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema, have been reported, but their causal relationships remain uncertain.

Renal adverse reactions with a probable causal relationship, but with a precise incidence unknown, include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, and hematuria. Renal papillary necrosis has also been reported, but its causal relationship is uncertain.

Miscellaneous reactions with a probable causal relationship, but with a precise incidence unknown, include dry eyes and mouth, gingival ulcer, and rhinitis.

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

It is important to note that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with the duration of use. Furthermore, NSAIDs are associated with an increased risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These events can occur at any time during use and without warning symptoms, with elderly patients being at greater risk for serious gastrointestinal events.

Drug Interactions

ACE inhibitors may exhibit reduced antihypertensive efficacy when administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs). Clinicians should consider this interaction when prescribing these medications together, particularly in patients who are using both classes concurrently. Monitoring of blood pressure and renal function may be warranted in such cases to ensure therapeutic effectiveness and patient safety.

No information regarding drug and laboratory test interactions is available.

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 this medication in children. Further studies are needed to determine appropriate dosing and outcomes in this population.

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 specific risks that healthcare professionals should consider. The use of NSAIDs around 30 weeks of gestation or later is particularly concerning, as it can lead to premature closure of the fetal ductus arteriosus. Additionally, the use of NSAIDs at approximately 20 weeks of gestation or later has been linked to fetal renal dysfunction, which may result in oligohydramnios and, in some instances, neonatal renal impairment.

To mitigate these risks, it is recommended that the use of Ibuprofen tablets be limited to the lowest effective dose and the shortest duration possible if necessary after 20 weeks of gestation. If treatment extends beyond 48 hours, monitoring with ultrasound for oligohydramnios should be considered. In cases where oligohydramnios is detected, discontinuation of Ibuprofen tablets is advised, followed by appropriate clinical follow-up.

Data from observational studies regarding other potential embryofetal risks associated with NSAID use during the first and second trimesters remain inconclusive. While reproductive studies in rats and rabbits have not shown evidence of developmental abnormalities, animal reproduction studies are not always predictive of human outcomes. Prostaglandins play a crucial role in various reproductive processes, and animal studies have indicated that the administration of prostaglandin synthesis inhibitors, such as ibuprofen, may lead to increased pre- and post-implantation loss and impair kidney development at clinically relevant doses.

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

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

Due to methodological limitations in postmarketing studies, including the absence of control groups and limited data on dosage and duration of exposure, establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use remains challenging. Consequently, 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 administration of an NSAID 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 discontinued, recovery to the pretreatment state is typically observed.

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 for these patients. If initiation of Ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's renal function is advised.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when administered 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 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, 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.

It is advisable to assess liver function prior to initiating NSAID therapy and to consider dose adjustments or alternative treatments in patients with significant hepatic impairment. Regular monitoring of renal parameters is also recommended to mitigate the risk of renal complications in this population.

Overdosage

In cases of ibuprofen overdose, significant symptoms and management strategies must be understood to ensure appropriate care.

Symptoms of Overdosage Severe overdose can manifest within approximately 1.5 hours post-ingestion. For instance, a child who ingested 7 to 10 ibuprofen tablets (400 mg) exhibited apneic and cyanotic symptoms, indicating a critical state. Additionally, a 19-year-old male who consumed 8,000 mg of ibuprofen experienced dizziness and nystagmus, further suggesting significant toxicity.

Management Procedures In instances of acute overdose, it is imperative to empty the stomach through vomiting or gastric lavage within one hour of ingestion to facilitate effective decontamination. The administration of oral activated charcoal may also be beneficial, as it can help reduce both the absorption and reabsorption of ibuprofen in overdose scenarios.

Given the acidic nature of ibuprofen, administering alkali and inducing diuresis may provide additional therapeutic benefits. Blood levels of ibuprofen can escalate to 700 µg/mL during an overdose, which is approximately ten times the peak levels observed in normal absorption-excretion studies.

Supportive Care Supportive measures are essential for recovery in cases of ibuprofen overdose. This includes ensuring adequate hydration and continuous monitoring of the patient’s condition. These interventions are crucial to mitigate the effects of the overdose and promote patient safety.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, during pregnancy has been associated with teratogenic effects, particularly when administered around 30 weeks of gestation and later. The use of these medications can lead to premature closure of the fetal ductus arteriosus and fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment. Adverse outcomes related to fetal renal dysfunction may 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 interventions like exchange transfusion or dialysis were necessary.

Data from observational studies regarding other potential embryofetal risks associated with NSAID use during the first or second trimesters of pregnancy remain inconclusive. Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, animal reproduction studies do not always predict human responses. Prostaglandins play a crucial role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has resulted in 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.

Long-term administration of NSAIDs has been linked to renal papillary necrosis and other forms of renal injury. Renal toxicity has also been observed in patients where renal prostaglandins are vital for 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. Individuals at heightened risk for this reaction include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Typically, discontinuation of NSAID therapy results in recovery to the pretreatment state.

In studies involving rats, the administration of NSAIDs, similar to other drugs that inhibit prostaglandin synthesis, has been associated with an increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of Ibuprofen tablets on labor and delivery in pregnant women remain unknown.

Postmarketing Experience

During post-approval use of ibuprofen, the following 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.

Skin and Appendages: Reports 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 and periodically throughout the course of ongoing therapy. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be advised to be alert for symptoms of cardiovascular thrombotic events, which may include chest pain, shortness of breath, weakness, or slurring of speech. They should be instructed to report any of these symptoms to their healthcare provider immediately.

It is important to inform patients 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. Patients should be made aware that serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms. They 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 observe any indicative signs or symptoms.

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

Healthcare providers should inform patients to 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 arise.

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

Finally, healthcare providers should inform pregnant women 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.

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). Temporary excursions are permissible between 15º to 30ºC (59º to 86ºF), as defined by USP Controlled Room Temperature guidelines. It is essential to avoid exposure to excessive heat, specifically temperatures exceeding 40ºC (104ºF). Proper storage conditions are critical to maintaining the integrity and efficacy of the product.

Additional Clinical Information

Physicians are advised to monitor patients for signs or symptoms of gastrointestinal (GI) bleeding, as serious ulcerations and bleeding can occur without warning. For patients undergoing long-term treatment with NSAIDs, it is recommended that clinicians periodically check complete blood counts (CBC) and chemistry profiles. If any clinical signs or symptoms indicative of liver or renal disease arise, or if systemic manifestations such as eosinophilia or rash develop, or if abnormal liver tests persist or worsen, discontinuation of ibuprofen tablets is warranted.

In the postmarketing experience, several adverse reactions have been reported following the approval of ibuprofen, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

FDA Insert (PDF)

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

View full prescribing information (PDF)