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 provided below.

These tablets are classified as a nonsteroidal anti-inflammatory drug (NSAID) and are formulated for oral administration in dosages of 400 mg, 600 mg, and 800 mg. The inactive ingredients include colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, 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

Healthcare professionals should carefully consider the potential benefits and risks of ibuprofen tablets and other treatment options before initiating therapy. It is recommended to use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

After assessing the response to initial therapy with ibuprofen tablets, the dose and frequency should be adjusted to meet the specific needs of the patient. The total daily dose should not exceed 3200 mg. In cases where gastrointestinal complaints arise, ibuprofen tablets should be administered with meals or milk to mitigate these effects.

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 daily (qid) or as 400 mg, 600 mg, or 800 mg three to four times daily (tid or qid). The dosage should be tailored to each patient, with adjustments made based on the severity of symptoms at the initiation of therapy or in response to treatment.

It is noted that patients with rheumatoid arthritis may require higher doses of ibuprofen tablets compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should be utilized.

For the relief of mild to moderate pain, a dose of 400 mg may be taken every 4 to 6 hours as needed. In the case of dysmenorrhea, ibuprofen tablets should be administered at the onset of pain, starting with a dose of 400 mg every 4 hours as necessary for pain relief.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Use is also contraindicated in individuals who have a history of asthma, urticaria, or allergic-type reactions following the administration of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), due to the risk of severe, potentially fatal anaphylactic-like reactions. Additionally, ibuprofen tablets should not be administered in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, are associated with the use of NSAIDs, including ibuprofen tablets. These events can be fatal, and the risk may increase with the duration of use. Ibuprofen tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs are also linked to serious gastrointestinal (GI) adverse events, such as bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events may occur at any time during treatment and can happen without warning symptoms. Elderly patients are particularly at increased risk for serious gastrointestinal complications. Physicians should monitor patients on long-term NSAID therapy for signs or symptoms of GI bleeding.

Anaphylactoid reactions may occur in individuals without prior exposure to ibuprofen tablets. In such cases, emergency medical assistance should be sought immediately. Additionally, serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can arise without warning. Patients should discontinue ibuprofen tablets at the first sign of a skin rash or any other indication of hypersensitivity.

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

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

For patients receiving long-term NSAID treatment, it is advisable to periodically check complete blood count (CBC) and chemistry profiles. If any clinical signs or symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued.

In summary, healthcare professionals should remain vigilant for potential adverse events associated with ibuprofen tablets and ensure appropriate monitoring and patient education regarding the signs and symptoms that necessitate immediate medical attention.

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. The risk of these events may arise 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 gastrointestinal reactions reported include nausea, epigastric pain, heartburn, diarrhea, abdominal distress, and constipation. More severe gastrointestinal issues such as gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis have also been observed.

Central nervous system reactions may manifest as dizziness, headache, and nervousness. More serious effects include depression, insomnia, confusion, emotional liability, and somnolence. Rarely, aseptic meningitis with fever and coma, as well as hallucinations and dream abnormalities, have been reported.

Dermatologic reactions can range from mild rashes and pruritis to severe conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and photoallergic skin reactions.

Hematologic adverse reactions include neutropenia, agranulocytosis, aplastic anemia, and hemolytic anemia, with some cases being Coombs positive. Patients may also experience thrombocytopenia and 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, and arrhythmias such as sinus tachycardia and bradycardia.

Allergic reactions may present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, with severe cases leading to anaphylaxis and bronchospasm. Other allergic manifestations include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

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

Miscellaneous reactions may involve dry eyes and mouth, gingival ulcers, and rhinitis.

Healthcare providers should monitor patients for these adverse reactions and weigh the benefits against the risks when prescribing this medication.

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 who are concurrently taking 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 aspirin, 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.

In summary, careful consideration and monitoring are essential when ibuprofen is prescribed alongside these medications to mitigate potential adverse effects and ensure therapeutic efficacy.

Packaging & NDC

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

Pediatric Use

The safety and effectiveness of ibuprofen tablets in pediatric patients have not been established. Therefore, caution should be exercised when considering the use of ibuprofen in this population. Further studies are needed to determine appropriate dosing and outcomes in children.

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 closely monitor this population for potential adverse effects and to consider appropriate dosage adjustments based on individual patient needs and responses.

Pregnancy

Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities; however, it is important to note that animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Therefore, ibuprofen tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, particularly the closure of the ductus arteriosus, use during late pregnancy should be avoided. Additionally, the effects of ibuprofen tablets on labor and delivery in pregnant women are unknown. Healthcare professionals should carefully consider these factors when prescribing ibuprofen to pregnant patients.

Lactation

It is not known whether this drug is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants from ibuprofen tablets, lactating mothers should consider the importance of the drug to their health when making a decision to either discontinue nursing or discontinue the drug.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. 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 studies regarding the use of ibuprofen tablets in patients with advanced renal disease, treatment with ibuprofen is not recommended in this population. If ibuprofen 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. 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 precipitate renal decompensation.

Patients at greatest 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 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 and management strategies 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 between 7 to 10 ibuprofen tablets (400 mg). Approximately 1½ hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli. Despite the severity of the symptoms, this stimulus was sufficient to induce respiration. Upon examination, a greenish-yellow fluid was aspirated from the stomach, 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 apnea lasting 5 to 10 seconds. The child was subsequently admitted to intensive care, where sodium bicarbonate, dextrose, and normal saline were administered. By four hours post-ingestion, the child was more alert, able to sit independently, and responsive to 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 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 after 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 reported dizziness, and nystagmus was observed. Following hospitalization, the patient received parenteral hydration and was placed on bed rest for three days, after which he recovered without any reported sequelae.

Management Strategies

In instances of acute ibuprofen overdosage, it is recommended to empty the stomach through vomiting or gastric lavage; however, it is important to note that little drug may be recovered 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 implemented, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant in monitoring patients for potential complications and ensure appropriate supportive care is provided throughout the management of ibuprofen overdosage.

Nonclinical Toxicology

Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, it is important to note that animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Therefore, ibuprofen tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, specifically the closure of the ductus arteriosus, the use of ibuprofen during late pregnancy should be avoided.

Postmarketing Experience

In two postmarketing clinical studies, a greater incidence of decreased hemoglobin levels was observed compared to previous reports. Specifically, a decrease in hemoglobin of 1 gram or more occurred 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 reported in patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, potentially due to fluid retention, occult or gross gastrointestinal blood loss, or an incompletely described effect on erythropoiesis. NSAIDs are known to inhibit platelet aggregation and may prolong bleeding time in some patients; however, their effect on platelet function is quantitatively less, of shorter duration, and reversible compared to aspirin. Patients who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or those receiving anticoagulants, should be monitored closely.

Aseptic meningitis, accompanied by fever and coma, has been reported on rare occasions in patients undergoing ibuprofen therapy. This condition appears to be more likely in patients with systemic lupus erythematosus and related connective tissue diseases, although cases have also been documented in individuals without underlying chronic diseases.

Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, have been reported. These events may occur without prior warning.

Reports indicate that NSAIDs may reduce the antihypertensive effect of ACE inhibitors, warranting consideration in patients taking both medications concurrently. While several short-term controlled studies have not demonstrated a significant effect of ibuprofen tablets on prothrombin times or other clotting factors in individuals on coumarin-type anticoagulants, caution is advised due to reports of bleeding associated with the use of ibuprofen and other NSAIDs in these patients.

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. They should be encouraged 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, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately.

Patients should be made aware 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. Although serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should seek medical advice upon observing any indicative signs or symptoms.

It is important for patients to understand the necessity of follow-up care. Healthcare providers should inform patients that ibuprofen tablets can also cause serious skin side effects, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Patients should be alert for signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity, such as itching, and should be instructed to stop the medication immediately if any type of rash develops and to contact their physician as soon as possible.

Patients should be advised to monitor for symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms occur. They should also be informed 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 discontinue therapy and seek immediate medical attention.

Patients should be made aware of the signs of an anaphylactoid reaction, including difficulty breathing and swelling of the face or throat, and should be instructed to seek immediate emergency help if these symptoms arise. In late pregnancy, as with other NSAIDs, 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 bleeding, as serious gastrointestinal 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 occur (e.g., eosinophilia, rash), or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Physicians are advised to monitor patients for any signs or symptoms indicative of gastrointestinal (GI) bleeding. For patients undergoing long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that clinicians periodically check complete blood counts (CBC) and chemistry profiles to ensure patient safety.

In cases where patients exhibit clinical signs and symptoms suggestive of liver or renal disease, or if systemic manifestations such as eosinophilia or rash occur, ibuprofen tablets should be discontinued. Additionally, if abnormal liver tests persist or worsen, immediate cessation of the medication is warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)