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. The tablets include inactive ingredients such as carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, polysorbate, and titanium dioxide. Ibuprofen is available in 400 mg, 600 mg, and 800 mg tablets 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

The lowest effective dose of Ibuprofen should be utilized for the shortest duration that aligns with individual patient treatment goals. Following the initial therapy, healthcare professionals should observe the patient's response and adjust the dose and frequency accordingly to meet the specific needs of the patient. The total daily dose must not exceed 3200 mg.

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, administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). The dosage should be individualized, with adjustments made based on the severity of symptoms. It is important to note that patients with rheumatoid arthritis may require higher doses compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should be employed.

In cases of mild to moderate pain, a dose of 400 mg may be administered every 4 to 6 hours as needed for pain relief. Clinical trials have indicated that doses exceeding 400 mg do not provide additional efficacy compared to this dose.

For the treatment of dysmenorrhea, a dosage of 400 mg every 4 hours may be given as necessary for pain relief. If gastrointestinal complaints arise, it is recommended to administer Ibuprofen tablets with meals or milk to mitigate these effects.

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 reported in these patients.

Furthermore, ibuprofen tablets are contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

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

The use of NSAIDs is also linked to serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events may occur at any time during treatment and often without warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal complications. Therefore, it is crucial to avoid Ibuprofen in patients with a recent myocardial infarction unless the anticipated benefits outweigh the risks of recurrent cardiovascular thrombotic events. If Ibuprofen is administered in such cases, patients should be closely monitored for signs of cardiac ischemia.

Additionally, NSAIDs, including Ibuprofen, may lead to the onset of new hypertension or exacerbate preexisting hypertension. Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the treatment duration. It is important to note that Ibuprofen may diminish the cardiovascular effects of certain therapeutic agents used in the management of heart failure.

Serious skin adverse reactions, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported with NSAID use, which can be fatal. Ibuprofen should be discontinued at the first sign of a skin rash or any other indication of hypersensitivity. Furthermore, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been observed in patients taking NSAIDs like Ibuprofen. If any signs or symptoms of DRESS occur, Ibuprofen should be discontinued immediately, and the patient should be evaluated without delay.

Ibuprofen tablets are not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids can lead to exacerbation of the underlying disease. For patients on prolonged corticosteroid therapy, a gradual tapering of corticosteroids is recommended if discontinuation is necessary.

The pharmacological effects of Ibuprofen in reducing fever and inflammation may obscure diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions.

Physicians should remain vigilant for signs or symptoms of gastrointestinal bleeding in patients on long-term NSAID treatment. Regular monitoring of complete blood count (CBC) and chemistry profiles is advised. 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.

In cases of an anaphylactoid reaction, emergency medical assistance should be sought immediately. If signs or symptoms of DRESS are present, Ibuprofen must be stopped, and the patient should be evaluated promptly.

Side Effects

Patients receiving treatment with this medication may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. The risk of these events may increase with the duration of use and can occur early in treatment. Additionally, there is a significant risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal events may occur at any time during treatment and without warning symptoms, with elderly patients being at greater risk.

Gastrointestinal reactions are common and may include nausea, epigastric pain, heartburn, diarrhea, abdominal distress, vomiting, indigestion, constipation, and abdominal cramps or pain. More severe gastrointestinal issues such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, jaundice, abnormal liver function tests, and pancreatitis have also been reported.

Central nervous system effects may manifest as dizziness, headache, and nervousness, with more serious conditions such as depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma noted in some patients.

Dermatologic reactions can range from common rashes and pruritus to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Postmarketing experiences have also reported exfoliative dermatitis and fixed drug eruptions.

Patients may experience auditory and visual disturbances, including tinnitus, hearing loss, amblyopia, conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic reactions include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia, and eosinophilia, along with bleeding episodes such as epistaxis and menorrhagia.

Metabolic and endocrine reactions may involve decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

Cardiovascular reactions can include edema, fluid retention, congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias.

Allergic reactions may present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis, bronchospasm, serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal adverse reactions may include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria, and renal papillary necrosis.

Miscellaneous reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

It is important for healthcare providers to monitor patients for these adverse reactions and to weigh the benefits and risks of treatment, particularly in populations at higher risk for serious events.

Drug Interactions

The concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents, particularly angiotensin-converting enzyme (ACE) inhibitors, may result in a diminished antihypertensive effect. Clinicians should monitor blood pressure and consider dosage adjustments of the antihypertensive medication as necessary.

In the context of antiplatelet therapy, ibuprofen at a dose of 400 mg has been shown to 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. For patients requiring low-dose aspirin for cardiovascular protection, healthcare providers should consider the use of NSAIDs that do not affect aspirin's antiplatelet efficacy or explore non-NSAID analgesic alternatives.

Additionally, when ibuprofen is taken alongside aspirin, there is a reduction in the protein binding of ibuprofen; however, this does not affect the clearance of free ibuprofen. Monitoring for potential changes in therapeutic effects is advised in patients receiving both medications.

Packaging & NDC

The table below lists all NDC Code configurations of Ibuprofen, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness of Ibuprofen tablets in pediatric patients have not been established. Therefore, caution should be exercised when considering the use of 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, 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

The use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen, in pregnant patients, particularly after approximately 20 weeks of gestation, is associated with significant fetal risks. Administration of NSAIDs during this period may lead to fetal renal dysfunction, resulting in oligohydramnios, which can occur as early as 48 hours after initiation of treatment. Oligohydramnios is often reversible upon discontinuation of the NSAID; however, prolonged cases may lead to serious complications such as limb contractures and delayed lung maturation.

Furthermore, the use of NSAIDs, including Ibuprofen, around 30 weeks of gestation and later is contraindicated due to the increased risk of premature closure of the fetal ductus arteriosus. In instances where NSAID treatment is deemed necessary between 20 and 30 weeks of gestation, it is recommended to limit the use of Ibuprofen to the lowest effective dose for the shortest duration possible. Healthcare providers should consider ultrasound monitoring of amniotic fluid if Ibuprofen is administered for more than 48 hours. Should oligohydramnios develop, Ibuprofen should be discontinued, and appropriate follow-up should be conducted in accordance with clinical practice guidelines.

In summary, the potential for adverse fetal outcomes necessitates careful consideration and monitoring when prescribing NSAIDs to pregnant patients, particularly during the later stages of pregnancy.

Lactation

There are no specific statements regarding the use of this medication in nursing mothers or lactation. Therefore, healthcare professionals should exercise caution when prescribing this medication to lactating mothers, as the effects on breastfed infants and the excretion of the drug in breast milk have not been established.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. In patients where renal prostaglandins play a compensatory role in maintaining renal perfusion, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow. This reduction can precipitate overt renal decompensation, particularly in patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.

Due to the lack of controlled clinical study data regarding the use of Ibuprofen tablets in patients with advanced renal disease, 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. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs, including Ibuprofen tablets. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a compensatory role in maintaining renal perfusion. In patients with compromised liver function, the administration of 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. Due to the lack of controlled clinical study data regarding the use of Ibuprofen tablets in patients with advanced renal disease, treatment with Ibuprofen is not recommended for these patients. 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.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the age and weight of the patient.

Clinical Presentation A notable case involved a 19-month-old child weighing 12 kg who ingested 7 to 10 ibuprofen tablets (400 mg). Approximately 1.5 hours post-ingestion, the child exhibited apneic and cyanotic symptoms, responding only to painful stimuli. Blood analysis conducted 8.5 hours after ingestion revealed an ibuprofen concentration of 102.9 mcg/mL. Conversely, in two separate instances involving children weighing around 10 kg who ingested approximately 120 mg/kg of ibuprofen, no acute intoxication or subsequent complications were observed.

In an adult case, a 19-year-old male ingested 8,000 mg of ibuprofen over a few hours, presenting with dizziness and nystagmus. He was hospitalized and subsequently recovered following bed rest.

Management of Overdosage In the event of acute ibuprofen overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage. However, it is important to note that if more than one hour has passed since ingestion, the likelihood of recovering significant amounts of the drug is minimal.

The administration of oral activated charcoal may be beneficial in reducing both the absorption and reabsorption of ibuprofen. Additionally, due to the acidic nature of ibuprofen, administering alkali and inducing diuresis may enhance urinary excretion of the drug.

Healthcare professionals should remain vigilant for symptoms of overdosage and implement appropriate management strategies promptly to mitigate potential complications.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen, during pregnancy has been associated with teratogenic effects, particularly when administered around 20 weeks gestation or later. Specifically, NSAID use at approximately 30 weeks gestation or later increases the risk of premature closure of the fetal ductus arteriosus. Additionally, administration of NSAIDs during this period may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment. Oligohydramnios may be reversible upon discontinuation of treatment; however, prolonged oligohydramnios can lead to complications such as limb contractures and delayed lung maturation. If NSAID treatment is deemed necessary between 20 and 30 weeks gestation, it is advised to limit Ibuprofen use to the lowest effective dose for the shortest duration possible, with consideration for ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours. In cases where oligohydramnios occurs, Ibuprofen should be discontinued, and follow-up should be conducted in accordance with clinical practice guidelines.

In terms of non-teratogenic effects, animal studies have indicated that the administration of prostaglandin synthesis inhibitors, including Ibuprofen, is associated with increased pre- and post-implantation loss. Prostaglandins play a crucial role in fetal kidney development, and published animal studies have reported that prostaglandin synthesis inhibitors can impair kidney development when given at clinically relevant doses.

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, it is important to note that animal reproduction studies do not always predict human responses.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown, as all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is reported to be between 2 to 4% and 15 to 20%, respectively.

Postmarketing Experience

During postapproval 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, such as ibuprofen, and periodically throughout the course of treatment. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be advised 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.

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 alert 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. The importance of follow-up in this regard should be emphasized.

Patients should also be made aware that ibuprofen tablets can cause serious skin side effects, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Although serious skin reactions may occur without warning, patients should be alert for signs and symptoms of skin reactions, blisters, fever, or other signs of hypersensitivity such as itching. They should be instructed to stop the medication immediately if any type of reaction occurs and to contact their healthcare provider as soon as possible.

Patients should be advised to be aware of symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms arise.

It is crucial 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 symptoms occur, patients should be instructed to discontinue 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 such cases, patients should be instructed to seek immediate emergency help.

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

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product at room temperature, ensuring that it is kept away from excessive heat, defined as temperatures exceeding 40°C (104°F). Proper storage conditions are crucial 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 occur, it is advised that Ibuprofen tablets be discontinued. Additionally, if abnormal liver tests persist or worsen, discontinuation of the medication is warranted.

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)