Ibuprofen

Description

Ibuprofen tablets contain the active ingredient ibuprofen, which is (±) -2 - (p-isobutylphenyl) propionic acid. Ibuprofen is a white powder with a melting point of 74-77° C. It is very slightly soluble in water (<1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone. Ibuprofen is available in 400 mg, 600 mg, and 800 mg tablets for oral administration. Inactive ingredients include carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, and polysorbate, as well as 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

For the treatment of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage ranges from 1,200 mg to 3,200 mg daily, administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). The total daily dose should not exceed 3,200 mg. Dosing should be individualized based on the severity of the patient's symptoms, allowing for adjustments as necessary.

For the management of mild to moderate pain, a dosage of 400 mg may be taken every 4 to 6 hours as needed for pain relief.

In cases of dysmenorrhea, a dosage of 400 mg is recommended every 4 hours as necessary for pain relief.

To minimize gastrointestinal discomfort, it is advised to administer ibuprofen tablets with meals or milk.

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

Pregnant women should be advised to avoid the use of Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) starting at 30 weeks of gestation due to the risk of premature closure of the fetal ductus arteriosus. Clinical trials have indicated an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which may be fatal. To minimize the potential risk of adverse cardiovascular events, it is recommended to use the lowest effective dose for the shortest duration possible.

NSAIDs are contraindicated in the context of coronary artery bypass graft (CABG) surgery. Additionally, patients treated with NSAIDs during the post-MI period have shown an increased risk of reinfarction, cardiovascular-related death, and all-cause mortality. Therefore, the use of Ibuprofen in patients with a recent MI should be approached with caution, weighing the benefits against the risks.

It is important to note that NSAIDs can lead to the onset of new hypertension or exacerbate preexisting hypertension. Serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation, which can be fatal, have also been associated with NSAID use. Long-term administration of NSAIDs has been linked to renal papillary necrosis and other forms of renal injury. Anaphylactoid reactions may occur even in patients without prior exposure to ibuprofen. Furthermore, NSAIDs can cause severe skin reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has also been reported in patients taking NSAIDs, including Ibuprofen.

Ibuprofen tablets are not intended to replace corticosteroids or to treat corticosteroid insufficiency. The pharmacological effects of Ibuprofen in reducing fever and inflammation may diminish the utility of these diagnostic signs in identifying complications of presumed noninfectious, painful conditions.

For patients on long-term NSAID treatment, it is essential to monitor for signs or symptoms of gastrointestinal bleeding. Regular checks of complete blood count (CBC) and chemistry profiles are recommended. If any clinical signs or symptoms indicative of liver or renal disease develop, Ibuprofen should be discontinued immediately.

In cases of an anaphylactoid reaction, emergency medical assistance should be sought without delay. Patients should be instructed to discontinue Ibuprofen and seek immediate evaluation if signs or symptoms of DRESS occur. Additionally, patients must be informed to stop using Ibuprofen tablets at the first appearance of a skin rash or any other indication of hypersensitivity.

Side Effects

Patients receiving treatment with this medication may experience a range of adverse reactions. 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 adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal events can occur at any time during treatment and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Common adverse reactions, occurring in greater than 1% but less than 3% of patients, include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, abdominal distress, vomiting, indigestion, constipation, abdominal cramps, and bloating. Central nervous system effects may include dizziness, headache, and nervousness. Dermatologic reactions such as rash (including maculopapular types) and pruritus have also been reported. Other common reactions include tinnitus, decreased appetite, edema, and fluid retention, which generally respond promptly to discontinuation of the drug.

Adverse reactions with a precise incidence unknown but occurring in less than 1% of patients include more serious gastrointestinal issues such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, jaundice, abnormal liver function tests, and pancreatitis. Central nervous system effects may include depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Dermatologic reactions may involve vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia.

Hematologic reactions such as neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, and eosinophilia have been noted. Cardiovascular issues may include congestive heart failure in patients with marginal cardiac function, elevated blood pressure, and palpitations. Renal adverse reactions can manifest as acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, and hematuria. Miscellaneous reactions include dry eyes and mouth, gingival ulcer, and rhinitis.

Reactions with a precise incidence unknown and a causal relationship that is also unknown include central nervous system effects such as paresthesias, hallucinations, dream abnormalities, and pseudotumor cerebri. Dermatologic reactions may include toxic epidermal necrolysis and photoallergic skin reactions. Special senses may be affected by conjunctivitis, diplopia, optic neuritis, and cataracts. Hematologic issues may present as bleeding episodes, including epistaxis and menorrhagia. Metabolic and endocrine reactions may include gynecomastia, hypoglycemic reactions, and acidosis. Cardiovascular reactions may involve arrhythmias, such as sinus tachycardia and sinus bradycardia. Allergic reactions may present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Renal reactions may include renal papillary necrosis.

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

Drug Interactions

The concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents, particularly ACE inhibitors, may result in a diminished antihypertensive effect. Clinicians should monitor blood pressure closely in patients receiving both classes of medications and consider dosage adjustments of the antihypertensive agent if necessary.

In the context of antiplatelet therapy, ibuprofen has been shown to interfere with the antiplatelet activity of aspirin. Specifically, when ibuprofen is administered at a dose of 400 mg prior to aspirin, this interaction is particularly pronounced. To mitigate this effect, it is advisable for patients to take immediate-release low-dose aspirin at least 2 hours before ibuprofen administration.

Due to the potential for increased adverse effects, the concomitant use of ibuprofen and aspirin is generally not recommended. Healthcare providers should exercise caution and consider alternative pain management strategies in patients who require 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 NSAIDs, including Ibuprofen, during pregnancy is associated with specific fetal risks, particularly when administered during the later stages of gestation. Pregnant patients should be advised to avoid NSAID use around 30 weeks of gestation and later due to the increased risk of premature closure of the fetal ductus arteriosus.

Additionally, the use of NSAIDs, including Ibuprofen, after approximately 20 weeks of gestation may lead to fetal renal dysfunction, which can result in oligohydramnios and, in some instances, neonatal renal impairment. These adverse effects may manifest after days to weeks of treatment; however, oligohydramnios has been reported as early as 48 hours following the initiation of NSAID therapy. While oligohydramnios is often reversible upon discontinuation of the medication, prolonged cases may lead to complications such as limb contractures and delayed lung maturation. In certain postmarketing reports, impaired neonatal renal function necessitated invasive interventions, including exchange transfusion or dialysis.

If Ibuprofen treatment is deemed necessary between 20 and 30 weeks of gestation, it is recommended to limit the dosage to the lowest effective amount for the shortest duration possible. Healthcare providers should consider ultrasound monitoring of amniotic fluid levels if Ibuprofen is used 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.

Lactation

There are no specific statements regarding the use of this medication in lactating mothers or its effects on breastfed infants. Healthcare professionals should consider the absence of data when advising lactating mothers about the use of this medication.

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 therapy with Ibuprofen tablets 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 critical 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 renal decompensation.

Patients at heightened 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 this population. If therapy with Ibuprofen tablets is deemed necessary, it is essential to closely monitor the patient's renal function throughout the treatment period. 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 patient's age and weight.

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. This highlights the potential severity of ibuprofen overdosage in young children.

Conversely, in two separate instances involving children weighing around 10 kg who ingested approximately 120 mg/kg of ibuprofen, no acute intoxication symptoms or late sequelae were observed. This suggests that while significant overdosage can lead to severe outcomes, certain levels of ingestion may not result in immediate adverse effects.

In adults, a case involving a 19-year-old male who consumed 8,000 mg of ibuprofen over several hours reported dizziness and nystagmus but ultimately recovered following hospitalization. This indicates that while high doses can lead to concerning symptoms, recovery is possible with appropriate medical intervention.

Management of ibuprofen overdosage should include the following recommended actions:

• Gastric Decontamination: In cases of acute overdosage, it is advisable to empty the stomach 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 low.

• Activated Charcoal: The administration of oral activated charcoal may be beneficial in reducing both the absorption and reabsorption of ibuprofen, particularly if given shortly after ingestion.

• Alkali Administration and Diuresis: Due to the acidic nature of ibuprofen, administering alkali and inducing diuresis may aid in the elimination of the drug from the body.

Healthcare professionals should remain vigilant for symptoms of overdosage and initiate 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 several teratogenic effects. 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. In animal studies, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, resulted in increased pre- and post-implantation loss. Prostaglandins play a crucial role in fetal kidney development, and published animal studies have indicated 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, prolonged oligohydramnios can lead to complications such as limb contractures and delayed lung maturation. In certain postmarketing cases of impaired neonatal renal function, invasive interventions, including 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, it is important to note that animal reproduction studies do not always predict human responses.

In summary, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, in animal studies has demonstrated increased pre- and post-implantation loss and potential impairment of kidney development, underscoring the need for caution in their use during pregnancy.

Postmarketing Experience

During postapproval use of ibuprofen, the following adverse reactions have been identified through voluntary reports and surveillance programs: exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE). These events were reported in the context of pharmacovigilance and are included for informational purposes.

Patient Counseling

Patients should be advised to remain vigilant for symptoms indicative of cardiovascular thrombotic events, such as 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 may cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, including ulcers and bleeding, which could lead to hospitalization or even death. Patients should be made aware of the signs and symptoms of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they observe any of these indicative signs or symptoms.

Patients should also be alerted to the potential for serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN). They should be instructed to discontinue ibuprofen tablets immediately if they develop any type of skin reaction or fever and to contact their healthcare provider as soon as possible.

Additionally, patients should be informed about the symptoms of congestive heart failure, which may include shortness of breath, unexplained weight gain, or edema. They should be advised to contact their healthcare provider if they experience any of these symptoms.

Patients must be made aware of the warning signs and symptoms of hepatotoxicity, such as 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.

It is crucial to inform patients about the signs of an anaphylactoid reaction, including difficulty breathing and swelling of the face or throat. They should be instructed to seek immediate emergency help if these symptoms arise.

In the context of pregnancy, patients should be advised to avoid ibuprofen tablets during late pregnancy due to the risk of premature closure of the ductus arteriosus. Pregnant women should be cautioned against 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 are advised to monitor 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, Ibuprofen tablets should 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 Cardinal Health 107, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)