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.

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 associated with rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in pediatric populations have not been conducted. Therefore, healthcare professionals should exercise caution when considering the use of ibuprofen in children.

Dosage and Administration

For the management of rheumatoid arthritis and osteoarthritis, 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 potentially benefiting from a higher dose of 3200 mg daily compared to 2400 mg. It is essential to tailor the dosage to each patient, adjusting 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. In cases of dysmenorrhea, the recommended dosage is 400 mg every 4 hours as necessary for pain relief.

The maximum total daily dose should not exceed 3200 mg. If gastrointestinal complaints arise, it is advised to administer Ibuprofen tablets with meals or milk to mitigate these effects.

Following the initial therapy, healthcare professionals should observe the patient's response and adjust the dose and frequency accordingly to meet individual needs. In chronic conditions, a therapeutic response is typically observed within two weeks, at which point the patient's dosage should be reviewed and modified 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, potentially fatal, anaphylactic-like reactions have been reported in these patients. Furthermore, ibuprofen tablets are contraindicated for the management of perioperative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

NSAIDs, including Ibuprofen tablets, are associated with significant risks that healthcare professionals must consider when prescribing and monitoring treatment.

Cardiovascular Risks The use of NSAIDs may elevate the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk is particularly heightened with prolonged use and in patients with existing cardiovascular disease or risk factors. Ibuprofen tablets are contraindicated for the treatment of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Gastrointestinal Adverse Events NSAIDs can lead to severe gastrointestinal complications, such as inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, which may be fatal. These adverse events can occur at any time during treatment, with or without prior warning symptoms. Physicians should monitor patients for signs or symptoms of gastrointestinal bleeding, especially those on long-term NSAID therapy.

Hypertension and Fluid Retention The initiation of NSAID treatment may result in new hypertension or exacerbate preexisting hypertension, potentially increasing the risk of cardiovascular events. Blood pressure should be closely monitored during the initiation and throughout the course of NSAID therapy. Additionally, fluid retention and edema have been reported in some patients; therefore, Ibuprofen tablets should be used cautiously in individuals with fluid retention or heart failure.

Renal Injury Long-term use of NSAIDs has been linked to renal papillary necrosis and other forms of renal injury. Patients at higher risk include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Regular monitoring of renal function is advised for these populations.

Anaphylactoid Reactions Anaphylactoid reactions may occur in patients without prior exposure to Ibuprofen tablets. In such cases, immediate emergency medical assistance should be sought.

Skin Reactions Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can occur with NSAID use. Discontinuation of Ibuprofen tablets is warranted at the first sign of a skin rash or any indication of hypersensitivity.

Pregnancy Considerations In late pregnancy, the use of Ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus.

Corticosteroid Considerations Ibuprofen tablets are not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids can lead to exacerbation of the underlying condition; therefore, patients on long-term corticosteroid therapy should have their medication tapered gradually if discontinuation is necessary.

Laboratory Monitoring Patients on long-term NSAID therapy should have their complete blood count (CBC) and chemistry profile monitored periodically. 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.

Healthcare professionals are advised to remain vigilant for these potential risks and to educate patients on the importance of reporting any concerning symptoms promptly.

Side Effects

Patients may experience a range of adverse reactions while using this medication, categorized by seriousness and frequency.

Serious adverse reactions include an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may escalate with prolonged use, particularly in patients with existing cardiovascular disease or risk factors. 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 may occur at any time during treatment and without warning symptoms, with elderly patients being at greater risk.

Common adverse reactions, occurring in more than 1% but less than 3% of patients, include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, abdominal distress, and constipation. Central nervous system effects such as dizziness, headache, and nervousness are also noted. Dermatologic reactions may manifest as rash (including maculopapular types) and pruritus. Patients may also experience tinnitus as a common adverse reaction.

Other adverse reactions with a precise incidence unknown but occurring in less than 1% of patients include gastrointestinal complications such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, and pancreatitis. Central nervous system effects may include depression, insomnia, confusion, and somnolence. Dermatologic reactions may extend to vesiculobullous eruptions, urticaria, and Stevens-Johnson syndrome.

Hematologic reactions such as neutropenia, agranulocytosis, and thrombocytopenia have been reported, although their precise incidence is unknown. Metabolic and endocrine effects may include decreased appetite and potential gynecomastia. Cardiovascular concerns may arise, including congestive heart failure in patients with marginal cardiac function and elevated blood pressure.

Allergic reactions, while rare, may include anaphylaxis and bronchospasm. Renal complications such as acute renal failure and decreased creatinine clearance have also been observed. Miscellaneous reactions may include dry eyes and mouth, gingival ulcer, and rhinitis.

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

Drug Interactions

Concomitant use of ACE-inhibitors and NSAIDs may lead to a reduction in the antihypertensive effect of the ACE-inhibitors. This interaction warrants careful consideration in patients who are prescribed both classes of medications. Monitoring of blood pressure is advised in these patients to ensure therapeutic efficacy and to make any necessary dosage adjustments.

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 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, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Therefore, ibuprofen 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 of ibuprofen during late pregnancy should be avoided. The effects of ibuprofen tablets on labor and delivery in pregnant women are currently 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 study data regarding the use of Ibuprofen tablets in patients with advanced renal disease, treatment with Ibuprofen is not recommended in this population. If initiation of Ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's renal function is advised. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs, including Ibuprofen tablets. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a compensatory role in maintaining renal perfusion. In patients with compromised liver function, the administration of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate overt renal decompensation.

Patients at greatest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. Due to the lack of controlled clinical study data regarding the use of Ibuprofen tablets in patients with advanced renal disease, treatment with Ibuprofen is not recommended for these individuals. If therapy with Ibuprofen tablets is deemed necessary, close monitoring of renal function is advised to mitigate the risk of renal toxicity. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

Overdosage

Approximately 1.5 hours following the ingestion of 7 to 10 ibuprofen tablets (400 mg) by a 19-month-old child weighing 12 kg, the child presented to the hospital emergency room in a state of apnea and cyanosis, responding only to painful stimuli. This stimulus was sufficient to induce respiration. Upon admission, the child received oxygen and parenteral fluids, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen. Two hours post-ingestion, the child's condition appeared stable; however, she continued to respond solely to painful stimuli and experienced intermittent apnea lasting 5 to 10 seconds. The child was subsequently admitted to intensive care, where sodium bicarbonate, along with infusions of dextrose and normal saline, was administered. By four hours after ingestion, the child could be easily aroused, sit independently, and respond to verbal commands. A blood level of ibuprofen measured 102.9 µg/mL approximately 8.5 hours post-ingestion, and by 12 hours, the child showed complete recovery.

In two additional reported cases involving children, each weighing approximately 10 kg, accidental acute ingestion of approximately 120 mg/kg of ibuprofen resulted in no signs of acute intoxication or late sequelae. Notably, one child's blood level was recorded at 700 µg/mL 90 minutes after ingestion, which is about ten times the peak levels observed in absorption-excretion studies.

A case involving a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours presented with dizziness, and nystagmus was noted. Following hospitalization, the patient received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

In instances of acute overdosage, it is recommended that the stomach be emptied 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 theoretically 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.

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 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 than previously reported. 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.

Anaphylactoid reactions have been reported in patients without known prior exposure to ibuprofen tablets. It is advised that ibuprofen tablets not be administered to patients with the aspirin triad, a symptom complex typically seen in asthmatic patients who may experience rhinitis with or without nasal polyps, or who may exhibit severe bronchospasm after taking aspirin or other NSAIDs.

Aseptic meningitis, accompanied by fever and coma, has been observed on rare occasions in patients undergoing ibuprofen therapy. While this condition is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has also been reported in individuals without underlying chronic diseases.

Reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of ACE inhibitors. This potential interaction should be considered in patients taking NSAIDs concurrently with ACE inhibitors.

Clinical studies and postmarketing observations have demonstrated that ibuprofen tablets can diminish the natriuretic effect of furosemide and thiazides in some patients, likely due to the inhibition of renal prostaglandin synthesis. Patients receiving concomitant therapy with NSAIDs should be closely monitored for signs of renal failure and to ensure the efficacy of diuretics.

Several short-term controlled studies have not shown significant effects of ibuprofen tablets on prothrombin times or various other clotting factors in individuals on coumarin-type anticoagulants. However, bleeding has been reported in patients taking ibuprofen tablets alongside other NSAIDs and anticoagulants, necessitating caution when prescribing ibuprofen tablets to patients on anticoagulant therapy.

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as ibuprofen, and periodically throughout the course of treatment. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be made aware that ibuprofen, like other NSAIDs, may lead to serious cardiovascular (CV) side effects, including myocardial infarction (MI) or stroke, which could result in hospitalization or even death. Although serious CV events can occur without warning symptoms, patients should be vigilant for signs and symptoms such as chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to seek medical advice if they observe any of these indicative signs or symptoms and understand the importance of follow-up.

Additionally, patients should be informed that ibuprofen can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may also lead to hospitalization or death. Serious GI tract ulcerations and bleeding can occur without warning symptoms; therefore, patients should be alert for signs such as epigastric pain, dyspepsia, melena, or hematemesis. They should be instructed to seek medical advice if they experience any of these symptoms and to recognize the importance of follow-up.

Patients should also be made aware of the potential for serious skin side effects associated with ibuprofen, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Although serious skin reactions may occur without warning, patients should be vigilant for signs such as skin rash, blisters, fever, or other hypersensitivity symptoms like itching. They should be advised to discontinue the medication immediately if any rash develops and to contact their physician as soon as possible.

Patients should promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider. Furthermore, they should be informed about the warning signs and symptoms of hepatotoxicity, including 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, they should be instructed to seek immediate emergency help.

Finally, patients should be advised that ibuprofen should be avoided in late pregnancy, as it may cause premature closure of the ductus arteriosus.

Storage and Handling

The product is supplied in a tightly closed container to ensure stability and integrity. It should be stored at room temperature, specifically within the range of 20°C to 25°C (68°F to 77°F). Additionally, it is essential to protect the product from light exposure to maintain its efficacy.

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, discontinuation of the medication is advised.

FDA Insert (PDF)

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

View full prescribing information (PDF)