Ibuprofen

Description

Ibuprofen tablets USP contain the active ingredient ibuprofen, which is (±) - 2 - (p - isobutylphenyl) propionic acid. Ibuprofen appears as a white to off-white, crystalline powder with a melting point of 74 to 77°C. It is very soluble in alcohol, methanol, acetone, and chloroform, slightly soluble in ethyl acetate, and practically insoluble in water. Ibuprofen tablets USP are available in strengths of 400 mg, 600 mg, and 800 mg for oral administration. The inactive ingredients include colloidal silicon dioxide, croscarmellose sodium, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol-partially hydrolyzed, povidone, stearic acid, talc, 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

For the management of rheumatoid arthritis and osteoarthritis, the suggested dosage ranges from 1200 mg to 3200 mg daily. This can be administered as 300 mg four times a day (qid) or as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). Individual patient response may vary, and some patients may benefit from a total daily dose of 3200 mg compared to 2400 mg; however, careful monitoring for clinical benefits versus risks is essential. Dosing should be tailored to each patient and may be adjusted based on the severity of symptoms.

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

In cases of dysmenorrhea, the recommended dosage is 400 mg every 4 hours as necessary, initiated at the earliest onset of pain.

General administration guidelines stipulate that the total daily dose should not exceed 3200 mg. In instances of gastrointestinal complaints, it is advisable to administer ibuprofen tablets with meals or milk to mitigate discomfort. The smallest effective dose should be utilized for the shortest duration that aligns with the individual treatment goals of the patient.

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 and 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

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

NSAIDs, including ibuprofen tablets, can lead to severe gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which may be fatal. These serious adverse events can occur at any time, with or without warning symptoms. Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen tablets; therefore, ibuprofen should not be administered to patients with the aspirin triad. Additionally, NSAIDs can cause serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can also be fatal.

The use of NSAIDs, including ibuprofen tablets, in pregnant women at approximately 30 weeks gestation and later should be avoided due to the risk of premature closure of the fetal ductus arteriosus.

Ibuprofen tablets are not intended to replace corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may result in exacerbation of the underlying disease. Furthermore, the pharmacological effects of ibuprofen tablets in reducing fever and inflammation may obscure diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions.

For patients on long-term NSAID therapy, including ibuprofen tablets, it is recommended to monitor hemoglobin or hematocrit levels if any signs or symptoms of anemia are present. Patients who may be adversely affected by changes in platelet function, such as those with coagulation disorders or those receiving anticoagulants, should be closely monitored while on ibuprofen tablets.

In the event of an anaphylactoid reaction, emergency medical assistance should be sought immediately. Patients should be educated on the signs and symptoms of serious skin reactions and instructed to discontinue ibuprofen tablets at the first appearance of a skin rash or any other indication of hypersensitivity. If such signs or symptoms occur, the use of ibuprofen tablets should be stopped, and the patient should be evaluated without delay.

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 cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. These events may occur early in treatment and the risk may increase with prolonged use. Additionally, 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. Such events can occur at any time during treatment and may present without warning symptoms, particularly in elderly patients who are 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, hepatitis, 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 including depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis, which can lead to fever and coma. Other neurological symptoms may include paresthesias, hallucinations, dream abnormalities, and pseudo-tumor cerebri.

Dermatologic reactions can range from common rashes, including maculopapular types and pruritus, to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, and photoallergic skin reactions.

Adverse reactions affecting the special senses include tinnitus, hearing loss, amblyopia (blurred and/or diminished vision), conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic adverse reactions may include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, and decreases in hemoglobin and hematocrit. Patients may also experience bleeding episodes such as epistaxis and menorrhagia.

Metabolic and endocrine reactions can involve decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis. Cardiovascular reactions may include edema, fluid retention (which generally responds promptly to drug discontinuation), congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (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. Other allergic conditions reported include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal adverse reactions can include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria, and renal papillary necrosis. Miscellaneous reactions may involve dry eyes and mouth, gingival ulcer, and rhinitis.

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

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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

There is no pediatric use information available for this medication. Therefore, its safety and efficacy in pediatric patients, including infants, children, and adolescents, have not been established. Healthcare professionals should exercise caution when considering this medication for use in the pediatric population.

Geriatric Use

No information relevant to geriatric use is provided in the text. Therefore, healthcare providers should exercise caution when prescribing this medication to elderly patients, as the absence of specific data may indicate a lack of established safety and efficacy in this population. It is advisable to monitor geriatric patients closely for any adverse effects and to consider individual patient factors when determining treatment plans.

Pregnancy

Pregnant women are advised to avoid the use of ibuprofen tablets 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, which can lead to significant fetal complications.

If treatment with ibuprofen tablets is deemed necessary for a pregnant woman between approximately 20 to 30 weeks of gestation, it is recommended that she be monitored for oligohydramnios if the treatment extends beyond 48 hours. This precaution is essential to ensure fetal well-being and to mitigate potential adverse outcomes associated with prolonged NSAID use during this critical period of pregnancy.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers or its effects on lactation. Consequently, the potential for excretion in breast milk and the impact on breastfed infants remain undetermined. Healthcare professionals should exercise caution when considering this medication for lactating mothers, as the absence of data necessitates careful evaluation of the benefits and risks.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. In patients with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow, which can precipitate overt renal decompensation. Patients at the highest risk for these adverse effects 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.

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. If therapy with ibuprofen tablets is deemed necessary, close monitoring of renal function is advised.

The use of NSAIDs, including ibuprofen tablets, during pregnancy, particularly around 20 weeks gestation or later, may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes may occur after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours after initiation of NSAID therapy. While oligohydramnios is often reversible upon discontinuation of treatment, 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 like exchange transfusion or dialysis were required.

If NSAID treatment is necessary between approximately 20 weeks and 30 weeks gestation, it is recommended to limit the use of ibuprofen tablets to the lowest effective dose and the shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if treatment extends beyond 48 hours. Ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up conducted according to clinical practice guidelines.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a 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 renal decompensation.

Patients at the highest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Therefore, it is crucial to exercise caution when considering NSAID therapy in this population.

Currently, there is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Consequently, treatment with ibuprofen tablets is not recommended for these patients. If the initiation of ibuprofen tablet therapy is deemed necessary, close monitoring of renal function is advised to mitigate potential risks. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of careful patient management.

Overdosage

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

Clinical Presentation For instance, a 19-month-old child weighing 12 kg exhibited severe symptoms approximately 1½ hours after ingesting 7 to 10 ibuprofen tablets (400 mg). The child became apneic and cyanotic, responding only to painful stimuli. Blood levels of ibuprofen measured at 102.9 mcg/mL approximately 8½ hours post-ingestion indicate a significant exposure. Conversely, in two separate cases involving children weighing around 10 kg who ingested approximately 120 mg/kg, there were no signs of acute intoxication or subsequent complications.

In adults, a 19-year-old male who consumed 8,000 mg of ibuprofen over a few hours experienced dizziness and nystagmus but ultimately recovered following hospitalization.

Management Recommendations In instances of acute overdosage, it is critical to initiate decontamination measures promptly. The stomach should be emptied through vomiting or gastric lavage within 1 hour of ingestion to maximize effectiveness. The administration of oral activated charcoal may also be beneficial, as it can help reduce both the absorption and reabsorption of ibuprofen.

Additionally, due to the acidic nature of ibuprofen and its urinary excretion, administering alkali and inducing diuresis may provide further therapeutic advantages.

Healthcare professionals should remain vigilant for potential symptoms and manage each case based on the severity of the overdosage and the clinical presentation of the patient.

Nonclinical Toxicology

Taking nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy, particularly after approximately 20 weeks, may pose risks to the developing fetus. It is advised that NSAIDs not be used after around 30 weeks of gestation due to potential harm to the unborn child.

In rare instances, patients undergoing ibuprofen therapy have experienced aseptic meningitis, accompanied by symptoms such as fever and coma.

No additional specific data regarding nonclinical toxicology or animal pharmacology and toxicology is available.

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-related adverse reactions include exfoliative dermatitis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Patient Counseling

Patients should be informed of the symptoms associated with cardiovascular thrombotic events, which include chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to report any of these symptoms to their healthcare provider immediately.

It is important to communicate that ibuprofen tablets can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects such as ulcers and bleeding. These complications may lead to hospitalization and 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 these occur.

Patients should be advised to discontinue ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

Additionally, patients should be made aware of the symptoms of congestive heart failure, which include shortness of breath, unexplained weight gain, or edema. They should be instructed to contact their healthcare provider if such symptoms arise.

It is essential to inform patients about the warning signs and symptoms of hepatotoxicity, which may include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms. If these 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.

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

Storage and Handling

The product is supplied in accordance with the following specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), adhering to the guidelines set forth by USP Controlled Room Temperature. It is essential to avoid exposure to excessive heat, specifically temperatures exceeding 40°C (104°F), to maintain product integrity. Proper storage conditions are crucial for ensuring the efficacy and safety of the product.

Additional Clinical Information

Anemia may occur in patients receiving NSAIDs, including ibuprofen tablets, potentially due to fluid retention, gastrointestinal blood loss, or effects on erythropoiesis. Clinicians should monitor hemoglobin or hematocrit levels in patients on long-term NSAID therapy who exhibit signs of anemia. In postmarketing studies, a decrease in hemoglobin of 1 gram or more was noted in 17.1% of patients taking 1600 mg daily for osteoarthritis and in 22.8% of those taking 2400 mg daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were reported.

NSAIDs, including ibuprofen, inhibit platelet aggregation and may prolong bleeding time, although their effect is less significant and shorter in duration compared to aspirin. Patients with coagulation disorders or those on anticoagulants should be closely monitored for potential alterations in platelet function.

FDA Insert (PDF)

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

View full prescribing information (PDF)