Ibuprofen

Description

Ibuprofen tablets contain the active ingredient ibuprofen, which is chemically defined as (±) - 2 - (p - isobutylphenyl) propionic acid. Ibuprofen appears as a white powder with a melting point of 74-77°C. It is characterized by very slight solubility in water (less than 1 mg/mL) and is readily soluble in organic solvents such as ethanol and acetone. The structural formula of ibuprofen is represented below.

This nonsteroidal anti-inflammatory drug (NSAID) is formulated for oral administration and is available in tablet strengths of 400 mg, 600 mg, and 800 mg. The tablets also contain several inactive ingredients, including carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, polysorbate, 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 treatment 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). Individual patient responses may vary, with some patients demonstrating a better response to a total daily dose of 3200 mg compared to 2400 mg. It is essential to tailor the dose to each patient, adjusting based on the severity of symptoms.

General dosage guidelines indicate that the total daily dose should not exceed 3200 mg. To minimize gastrointestinal complaints, the medication should be administered with meals or milk. The smallest effective dose should always be employed.

For mild to moderate pain, a dosage of 400 mg may be taken every 4 to 6 hours as necessary for pain relief. In cases of dysmenorrhea, a dosage of 400 mg every 4 hours may be used as needed for pain relief.

Administration of the medication is facilitated by the availability of three tablet strengths, allowing for appropriate dosage adjustments. A therapeutic response is typically observed within a few days to a week, with most patients experiencing relief by two weeks. Following the achievement of a satisfactory response, it is recommended that the patient's dose be reviewed and adjusted as necessary.

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 for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Patients receiving Ibuprofen tablets should be aware of several critical warnings and precautions to ensure safe use and minimize potential risks.

Cardiovascular Risks Clinical trials have demonstrated that both COX-2 selective and nonselective NSAIDs, including Ibuprofen, are associated with an increased risk of serious cardiovascular (CV) thrombotic events, such as myocardial infarction (MI) and stroke, which may be fatal. This risk is particularly pronounced in patients with existing CV disease or risk factors, who exhibit a higher absolute incidence of serious CV events. The likelihood of CV thrombotic events increases with higher doses of NSAIDs. Therefore, it is advised to avoid the use of Ibuprofen in patients with a recent MI unless the anticipated benefits outweigh the risks of recurrent CV thrombotic events.

Gastrointestinal Risks NSAIDs, including Ibuprofen, can lead to severe gastrointestinal (GI) adverse events, such as inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, which can be fatal. Patients and healthcare providers should remain vigilant for signs and symptoms of GI ulcerations and bleeding during treatment. Special care is warranted for elderly or debilitated patients due to their heightened risk of GI complications.

Renal and Hypertensive Concerns The use of NSAIDs may result in 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 course. Long-term administration of NSAIDs has been linked to renal papillary necrosis and other forms of renal injury. Physicians should periodically check the complete blood count (CBC) and chemistry profile of patients on long-term NSAID therapy.

Anaphylactoid and Skin Reactions Anaphylactoid reactions can occur in patients without prior exposure to Ibuprofen, necessitating immediate emergency medical assistance in such cases. Additionally, NSAIDs have been associated with serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. The use of Ibuprofen should be discontinued at the first sign of a skin rash or any other indication of hypersensitivity.

Monitoring and Laboratory Tests Healthcare professionals should monitor patients for signs or symptoms of GI bleeding and assess liver and renal function. If clinical signs consistent with liver or renal disease develop, Ibuprofen should be discontinued.

General Precautions To minimize potential risks, it is recommended to use the lowest effective dose of Ibuprofen for the shortest duration necessary. Patients should be educated about the symptoms of serious CV events and the appropriate actions to take if they occur.

In summary, careful consideration of these warnings and precautions is essential for the safe administration of Ibuprofen tablets, ensuring that both patients and healthcare providers are adequately informed and vigilant throughout the treatment process.

Side Effects

The most frequent adverse reactions associated with Ibuprofen tablets are gastrointestinal effects, with clinical trials indicating that 4% to 16% of patients reported one or more gastrointestinal complaints. Serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, can occur at any time during treatment with NSAIDs, often without warning symptoms. Approximately 1% of patients treated for 3-6 months and 2-4% of those treated for one year may experience upper GI ulcers, gross bleeding, or perforation. The risk of serious gastrointestinal events increases with longer duration of therapy, and even short-term use carries risks, particularly in patients with a history of ulcer disease or gastrointestinal bleeding, who have over a ten-fold increased risk of GI bleeding. Other risk factors include concomitant use of oral corticosteroids or anticoagulants, smoking, alcohol use, older age, and poor general health status. Most spontaneous reports of fatal GI events occur in elderly or debilitated patients.

Cardiovascular effects are also a significant concern, as clinical trials of various COX-2 selective and nonselective NSAIDs have demonstrated an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. This risk appears to be similar in patients with and without known cardiovascular disease or risk factors, although those with known conditions have a higher absolute incidence of such events. Some observational studies suggest that the increased risk may begin within the first weeks of treatment, particularly at higher doses. Therefore, the use of Ibuprofen tablets in patients with a recent MI should be approached with caution, and monitoring for signs of cardiac ischemia is recommended.

Hypertension may also develop or worsen in patients taking NSAIDs, including Ibuprofen tablets, potentially contributing to an increased incidence of cardiovascular events. Patients on thiazides or loop diuretics may experience impaired responses to these therapies while taking NSAIDs, necessitating close monitoring of blood pressure during treatment.

The risk of heart failure and edema is highlighted by a meta-analysis indicating a two-fold increase in hospitalizations for heart failure among patients treated with COX-2 selective and nonselective NSAIDs compared to placebo. Fluid retention and edema have been reported in some patients, and the use of Ibuprofen tablets in those with severe heart failure should be avoided unless the benefits outweigh the risks.

Renal effects are also notable, as long-term NSAID use can lead to renal papillary necrosis and other forms of renal injury. Patients with compromised renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly are at greater risk for renal toxicity due to the dose-dependent reduction in prostaglandin formation and renal blood flow.

Anaphylactoid reactions may occur in patients without prior exposure to Ibuprofen tablets, and the medication should not be administered to individuals with the aspirin triad. Emergency assistance should be sought if such a reaction occurs.

Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can also arise from NSAID use, including Ibuprofen tablets, often without warning. Patients should be informed of the signs and symptoms of serious skin manifestations and discontinue use at the first indication of a rash or hypersensitivity.

Hematological effects, such as anemia, may occur due to fluid retention, occult or gross gastrointestinal blood loss, or effects on erythropoiesis. Patients on long-term NSAID therapy should have their hemoglobin or hematocrit monitored if they exhibit signs or symptoms of anemia. Additionally, NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients.

Aseptic meningitis, characterized by fever and coma, has been observed rarely in patients undergoing ibuprofen therapy. If symptoms of meningitis develop, the potential relationship to Ibuprofen tablets should be considered.

In clinical trials involving patients with rheumatoid arthritis, reported side effects were higher at doses of 3200 mg/day compared to doses of 2400 mg or less, although the increases in incidence remained within the previously reported ranges.

Drug Interactions

Concomitant use of certain medications with ibuprofen may lead to significant drug interactions, which can affect therapeutic outcomes and safety. The following interactions have been identified:

Pharmacodynamic Interactions

• ACE-Inhibitors: Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may reduce the antihypertensive effect of ACE-inhibitors. Clinicians should consider this interaction when prescribing NSAIDs to patients already receiving ACE-inhibitors.

• Diuretics: Ibuprofen has been shown to diminish the natriuretic effect of diuretics such as furosemide and thiazides in some patients, likely due to the inhibition of renal prostaglandin synthesis. Close monitoring for signs of renal failure and assessment of diuretic efficacy is recommended during concomitant therapy.

• Warfarin-Type Anticoagulants: While short-term studies have not demonstrated a significant effect of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, there is a documented risk of increased bleeding. The combination of ibuprofen and anticoagulants may lead to a higher risk of serious gastrointestinal bleeding. Caution is advised when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

• Aspirin: Co-administration of ibuprofen with aspirin may reduce the protein binding of ibuprofen, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction remains unclear, but the concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

• Lithium: Ibuprofen has been associated with elevated plasma lithium levels and decreased renal clearance of lithium. In a study, the mean minimum lithium concentration increased by 15%, and renal clearance decreased by 19% during concurrent administration. Patients receiving both ibuprofen and lithium should be monitored closely for signs of lithium toxicity.

• Methotrexate: NSAIDs, including ibuprofen, may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is warranted when administering NSAIDs alongside methotrexate.

H-2 Antagonists: Studies indicate that the co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine does not significantly affect ibuprofen serum concentrations, suggesting that no dosage adjustments are necessary in this context.

Healthcare providers should remain vigilant for these interactions and consider appropriate monitoring or dosage adjustments as necessary when prescribing ibuprofen in conjunction with these 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 (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

Pregnancy Category C. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities; however, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Ibuprofen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. The effects of Ibuprofen tablets on labor and delivery in pregnant women are unknown.

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. In patients with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs in these patients 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 effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. In cases where NSAID therapy is necessary, close monitoring of renal function is advisable. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

There is no available information from controlled clinical studies regarding the use of Ibuprofen tablets in patients with advanced renal disease; therefore, treatment with Ibuprofen tablets is not recommended for these patients.

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 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 patients with advanced renal disease. 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, 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 time elapsed since ingestion.

Clinical Presentation

A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg each). Approximately 1½ hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli, which was sufficient to induce respiration. Initial management included the administration of oxygen and parenteral fluids. Gastric aspiration yielded a greenish-yellow fluid, with no evidence of ibuprofen detected. Two hours after ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced intermittent apnea lasting 5 to 10 seconds. Following admission to intensive care, sodium bicarbonate, along with dextrose and normal saline infusions, were administered. By four hours post-ingestion, the child was more responsive, able to sit independently and follow verbal commands. A blood level of ibuprofen measured 102.9 μg/mL approximately 8½ hours after ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional cases involving children weighing approximately 10 kg who accidentally ingested about 120 mg/kg of ibuprofen, no signs of acute intoxication or late sequelae were observed. One child exhibited a blood level of 700 μg/mL 90 minutes post-ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

Another case involved a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours. He presented with dizziness and was noted to have nystagmus. After hospitalization, he received parenteral hydration and was placed on bed rest for three days, ultimately recovering without any reported sequelae.

Management Recommendations

In instances of acute ibuprofen overdosage, it is recommended to empty the stomach through vomiting or gastric lavage; however, it should be noted that minimal drug recovery is expected if more than one hour has passed since ingestion. Given the acidic nature of ibuprofen and its urinary excretion, administering alkali and inducing diuresis may be beneficial. Supportive measures should be prioritized, and the use of oral activated charcoal may assist in reducing both absorption and reabsorption of ibuprofen.

Healthcare professionals should remain vigilant for potential symptoms and manage accordingly, ensuring that supportive care is provided throughout the treatment process.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) during late pregnancy should be avoided due to their known effects on the fetal cardiovascular system, particularly concerning the closure of the ductus arteriosus.

Postmarketing Experience

In two postmarketing clinical studies, a greater incidence of decreased hemoglobin levels was reported than previously documented. Specifically, a decrease in hemoglobin of 1 gram or more was observed in 17.1% of 193 patients receiving 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients taking 2400 mg of ibuprofen daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were noted in these studies.

Anemia has been associated with the use of NSAIDs, including ibuprofen tablets. This may result from fluid retention, occult or gross gastrointestinal blood loss, or an incompletely understood effect on erythropoiesis. It is recommended that patients undergoing long-term treatment with NSAIDs, including ibuprofen tablets, have their hemoglobin or hematocrit levels monitored if they exhibit any signs or symptoms of anemia.

NSAIDs are known to inhibit platelet aggregation and may prolong bleeding time in some patients. While their effect on platelet function is quantitatively less, of shorter duration, and reversible compared to aspirin, patients receiving ibuprofen tablets who may be adversely affected by changes in platelet function—such as those with coagulation disorders or those on anticoagulants—should be closely monitored.

Aseptic meningitis, accompanied by fever and coma, has been reported on rare occasions in patients undergoing ibuprofen therapy. Although this condition is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has also been documented in individuals without underlying chronic conditions. If a patient on ibuprofen tablets develops signs or symptoms of meningitis, the potential association with ibuprofen should be considered.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, have been associated with NSAIDs, including ibuprofen tablets. These serious reactions may occur without prior warning. Patients should be informed of the signs and symptoms of serious skin manifestations, and the use of the drug should be discontinued at the first appearance of a skin rash or any other indication of hypersensitivity.

Patient Counseling

Patients should be informed of essential information before initiating therapy with a nonsteroidal anti-inflammatory drug (NSAID) and periodically throughout the course of treatment. It is important for patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients to be vigilant for symptoms of cardiovascular thrombotic events, which may include chest pain, shortness of breath, weakness, or slurring of speech. Patients should be instructed to report any of these symptoms to their healthcare provider immediately.

Patients should also be made aware of the signs and symptoms of ulcerations and bleeding. They should seek medical advice if they experience any indicative signs, such as epigastric pain, dyspepsia, melena, or hematemesis.

It is crucial to inform patients about the potential for serious skin manifestations. Patients should be advised to discontinue the use of the drug at the first appearance of a skin rash or any other sign of hypersensitivity.

Healthcare providers should encourage patients to be alert for symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema. Patients should be instructed to contact their healthcare provider if such symptoms occur.

Patients must be informed about the warning signs and symptoms of hepatotoxicity, which may include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms. If these symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should also be educated on the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat. In such cases, patients should be advised to seek immediate emergency help.

In late pregnancy, as with other NSAIDs, patients should be informed that Ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus.

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

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product at room temperature, ensuring that the storage environment does not exceed 40°C (104°F) to maintain product integrity. Care should be taken to avoid exposure to excessive heat during storage and handling.

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 or rash occur, it is crucial to discontinue Ibuprofen tablets. Additionally, if abnormal liver tests persist or worsen, the medication should also be stopped to prevent further complications.

FDA Insert (PDF)

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

View full prescribing information (PDF)