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

The suggested dosage for the management of rheumatoid arthritis and osteoarthritis is 1200 mg to 3200 mg daily, administered in divided doses of 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 therapeutic effect at a total daily dose of 3200 mg compared to 2400 mg. Dosing should be tailored to each patient, with adjustments made 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, 400 mg can be administered every 4 hours as necessary for pain relief.

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

Following the initial therapy, healthcare professionals should monitor 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 a few days to a week, with most patients responding by two weeks. After achieving a satisfactory response, it is advisable to review and adjust the patient's dosage 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

Patients receiving Ibuprofen tablets should be aware of several critical warnings and precautions associated with their use.

Cardiovascular Risks Nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen, are associated with 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 for cardiovascular conditions. It is essential for healthcare professionals to evaluate the cardiovascular status of patients prior to initiating therapy.

Contraindications 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 (GI) complications, 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 during treatment, with or without prior warning symptoms. Healthcare providers should monitor patients closely for signs of GI bleeding.

Hypertension Monitoring The use of NSAIDs, including Ibuprofen, may result in the onset of new hypertension or exacerbate preexisting hypertension, potentially increasing the risk of cardiovascular events. Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the treatment duration.

Fluid Retention and Edema Fluid retention and edema have been reported in some patients taking NSAIDs. Caution is advised when prescribing Ibuprofen tablets to patients with a history of 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 heightened risk include those with impaired renal function, heart failure, liver dysfunction, those on diuretics or ACE inhibitors, and the elderly. Regular monitoring of renal function is recommended for these patients.

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

Serious Skin Reactions NSAIDs, including Ibuprofen, can cause severe skin reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Discontinuation of the drug is warranted at the first sign of a skin rash or any indication of hypersensitivity.

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

General Precautions 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; therefore, patients on long-term corticosteroid therapy should have their medication tapered gradually if discontinuation is necessary. Additionally, 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.

Laboratory Monitoring Healthcare professionals should monitor patients for signs or symptoms of GI bleeding. For those on long-term NSAID therapy, periodic complete blood count (CBC) and chemistry profile assessments are recommended. If clinical signs indicative of 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.

Emergency Situations Emergency medical help should be sought immediately in cases of anaphylactoid reactions. Furthermore, the use of Ibuprofen should be stopped and a healthcare provider contacted at the first appearance of a skin rash or any other sign of hypersensitivity.

Side Effects

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

Serious adverse reactions include an increased risk of 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 events, such as bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal complications can occur at any time during treatment and may present without warning symptoms. Elderly patients are particularly susceptible to these serious gastrointestinal events.

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 and pruritus, while tinnitus is a common auditory complaint. Patients may also experience decreased appetite as a metabolic/endocrine reaction, and cardiovascular issues such as edema and fluid retention have been reported.

Less common adverse reactions, with a precise incidence of less than 1%, include gastrointestinal complications such as gastric or duodenal ulcers with bleeding 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 severe conditions like Stevens-Johnson syndrome. Special senses may be affected by hearing loss and amblyopia. Hematologic reactions such as neutropenia, agranulocytosis, and thrombocytopenia have also been observed.

Other adverse reactions with unknown causal relationships include renal issues like acute renal failure and renal papillary necrosis, as well as allergic reactions such as anaphylaxis and angioedema. Patients may also report miscellaneous symptoms like dry eyes and mouth, gingival ulcers, and rhinitis.

It is essential 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

Reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive efficacy of angiotensin-converting enzyme (ACE) inhibitors. This interaction warrants careful consideration in patients who are receiving both NSAIDs and ACE inhibitors concurrently.

Healthcare professionals should monitor blood pressure closely in patients taking these medications together. If a significant reduction in the antihypertensive effect is observed, dosage adjustments of the ACE inhibitor may be necessary to achieve the desired therapeutic outcome.

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. 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 during late pregnancy should be avoided.

In animal studies, NSAIDs have been associated with an increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of ibuprofen on labor and delivery in pregnant women are unknown. Healthcare professionals should carefully consider the risks and benefits 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 critical role in maintaining renal perfusion. In patients with compromised liver function, the administration of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate renal decompensation.

Patients at 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 patient's age and weight.

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 1.5 hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli. Despite this, the painful stimulus was sufficient to induce respiration. Initial management included the administration of oxygen and parenteral fluids, along with gastric aspiration, which revealed a greenish-yellow fluid with no evidence of ibuprofen. 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, dextrose, and normal saline infusions 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 8.5 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.

A separate case involved a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours. He reported dizziness, and nystagmus was observed. After hospitalization, he received parenteral hydration and underwent three days of bed rest, 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 is important to note 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 the absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant for potential symptoms and manage each case based on the individual patient's presentation and clinical status.

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 compared to previous reports. Specifically, a decrease in hemoglobin of 1 gram or more occurred in 17.1% of 193 patients taking 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients receiving 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. This may be attributed to factors such as 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 generally less pronounced, of shorter duration, and reversible compared to aspirin. Patients who may be adversely affected by changes in platelet function, such as those with coagulation disorders or those receiving anticoagulants, should be monitored closely.

Rare cases of aseptic meningitis, accompanied by fever and coma, have been reported in patients undergoing ibuprofen therapy. While this condition is more likely to occur in individuals with systemic lupus erythematosus and related connective tissue diseases, it has also been documented in patients without underlying chronic conditions.

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 unexpectedly. Furthermore, there are reports indicating that NSAIDs may reduce the antihypertensive effect of ACE inhibitors. Clinical studies and postmarketing observations have also demonstrated that ibuprofen tablets can diminish the natriuretic effect of furosemide and thiazides in some patients. The concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as ibuprofen, and periodically during the course of ongoing therapy. They should be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should discuss the potential for serious cardiovascular (CV) side effects associated with ibuprofen tablets, including myocardial infarction (MI) and stroke, which may result in hospitalization or death. Patients should be made aware that serious CV events can occur without warning symptoms. They should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, and slurring of speech, and should seek medical advice if they observe any indicative signs or symptoms. The importance of follow-up in these cases should be emphasized.

It is also crucial to inform patients that ibuprofen tablets can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects, including ulcers and bleeding, which may lead to hospitalization or death. Patients should be advised to be vigilant for signs and symptoms of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis. They should seek medical advice if they experience any of these symptoms, and the importance of follow-up should be highlighted.

Patients should be made aware of the risk of serious skin side effects associated with ibuprofen tablets, 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 alert for signs and symptoms such as skin rash, blisters, fever, or other signs of hypersensitivity like itching. They 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 promptly report any signs or symptoms of unexplained weight gain or edema to their physicians. Additionally, 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 occur, patients should be instructed to discontinue therapy and seek immediate medical attention.

Healthcare providers should also educate patients on the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. Patients should be advised to seek immediate emergency help if these symptoms occur.

Finally, it should be communicated that ibuprofen tablets should be avoided in late pregnancy, as with other NSAIDs, due to the risk of causing premature closure of the ductus arteriosus.

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 to maintain its integrity and efficacy. Additionally, the product must be protected from light to prevent degradation. Proper handling and storage conditions are crucial to ensure the product remains effective throughout its shelf life.

Additional Clinical Information

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as serious ulcerations and bleeding may occur without warning. For patients undergoing long-term treatment with nonsteroidal anti-inflammatory drugs (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 develop, it is crucial to discontinue the use of Ibuprofen tablets. Additionally, if abnormal liver tests persist or worsen, cessation 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)