Ibuprofen

Description

Ibuprofen Tablets, USP 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 its very slight solubility in water (less than 1 mg/mL) and its ready solubility in organic solvents such as ethanol and acetone. These tablets are classified as a nonsteroidal anti-inflammatory drug (NSAID) and are available in dosages of 400 mg, 600 mg, and 800 mg for oral administration.

The formulation includes several inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, talc, stearic acid, and titanium dioxide.

Uses and Indications

Ibuprofen Tablets, USP are indicated for the relief of the signs and symptoms associated with rheumatoid arthritis and osteoarthritis. This medication is also 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, USP in pediatric populations have not been conducted. Therefore, the use of this medication in children is not recommended until further data is available.

Dosage and Administration

For the management of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage ranges from 1200 mg to 3200 mg daily. This can be administered as 300 mg four times a day (qid) or as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). It is imperative that the total daily dose does not exceed 3200 mg.

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.

To minimize gastrointestinal complaints, it is advised to administer Ibuprofen Tablets, USP with meals or milk.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of ibuprofen is not recommended 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). Furthermore, ibuprofen tablets are contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Clinical trials have demonstrated an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). This risk is particularly pronounced in patients with existing CV disease or risk factors. It is recommended that the lowest effective dose of NSAIDs be utilized for the shortest duration necessary. Healthcare professionals should educate patients on recognizing the signs and symptoms of serious CV events and advise them on the appropriate actions to take should these occur. Notably, there is no consistent evidence that the concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events linked to NSAID use; in fact, combining aspirin with an NSAID may elevate the risk of serious gastrointestinal (GI) events. Additionally, two large clinical trials have indicated a heightened incidence of myocardial infarction and stroke in patients treated with a COX-2 selective NSAID following coronary artery bypass graft (CABG) surgery.

NSAIDs may also induce new hypertension or exacerbate preexisting hypertension, which can lead to an increased incidence of CV events. Therefore, it is essential to monitor blood pressure closely during NSAID therapy.

Patients with a history of fluid retention or heart failure should be treated with caution, as NSAIDs have been associated with fluid retention and edema.

The use of NSAIDs carries a significant risk of serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation, which can be fatal. These events may occur unexpectedly, with or without warning symptoms. Patients with a prior history of ulcer disease or GI bleeding are at more than a tenfold increased risk for developing a GI bleed. Special vigilance is warranted for elderly or debilitated patients. Both patients and healthcare providers should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and should initiate prompt evaluation and treatment if a serious GI event is suspected.

Long-term use of NSAIDs can lead to renal injury, particularly in patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy typically results in recovery of renal function. Treatment with ibuprofen tablets is contraindicated in patients with advanced renal disease; if therapy is deemed necessary, close monitoring of renal function is advised.

Anaphylactoid reactions may occur in individuals without prior exposure to ibuprofen. It is contraindicated in patients with the aspirin triad, and emergency medical assistance should be sought immediately in the event of an anaphylactoid reaction.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported with NSAID use. Discontinuation of the drug is advised at the first sign of a skin rash or any other indication of hypersensitivity.

In late pregnancy, ibuprofen should be avoided due to the risk of premature closure of the ductus arteriosus.

Healthcare professionals should ensure that patients are aware of the need to seek emergency medical help in the event of an anaphylactoid reaction and to discontinue use and contact their physician 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, categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular events such as myocardial infarction, stroke, and other thrombotic events, which can be fatal. The risk of these events may increase with prolonged use, particularly in patients with existing cardiovascular disease or risk factors. Gastrointestinal complications, including bleeding, ulceration, and perforation of the stomach or intestines, are also serious and can occur without warning. Elderly patients are at a heightened risk for these gastrointestinal events. Additionally, renal effects such as acute renal failure and renal papillary necrosis have been reported, particularly with long-term use.

Common adverse reactions reported in clinical trials and postmarketing experiences include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, and constipation. Central nervous system effects such as dizziness, headache, and nervousness are also frequently observed. Dermatologic reactions, including rash and pruritus, have been noted, along with more severe skin reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis.

Other notable adverse reactions include hematologic issues such as neutropenia and thrombocytopenia, as well as metabolic/endocrine effects like decreased appetite and gynecomastia. Cardiovascular symptoms may manifest as edema and fluid retention, while patients may also experience tinnitus and various visual disturbances affecting the special senses.

Patients should be aware of the potential for allergic reactions, including anaphylaxis and angioedema, as well as miscellaneous effects such as dry eyes and mouth. It is essential for patients to monitor for these adverse reactions and consult healthcare providers as necessary.

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 in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of NSAIDs and anticoagulants may lead to a synergistic effect on 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 is 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 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 minimal interaction in this context.

In summary, careful consideration and monitoring are advised when ibuprofen is used in conjunction with 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

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, specifically those aged 65 years and older. Due to the potential for altered pharmacokinetics and increased sensitivity to medications in this population, careful consideration of dosage adjustments and monitoring is essential. Healthcare providers are advised to assess the individual health status and comorbidities of geriatric patients to ensure safe and effective treatment.

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 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. In rat studies involving NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, there was an increased incidence of dystocia, delayed parturition, and decreased pup survival. 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 individuals 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 the highest risk for these adverse effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. 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 in this population. If therapy with ibuprofen tablets is deemed necessary, close monitoring of the patient's renal function is advised.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this drug. Consequently, there are no dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the prescribing information.

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. This stimulus was sufficient to induce respiration. Upon examination, oxygen and parenteral fluids were administered, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen. 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, along with dextrose and normal saline infusions, were provided. 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 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 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. Following 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 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 beneficial. Supportive measures are essential, and the use of oral activated charcoal can be considered to reduce both absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant in monitoring patients for potential complications and provide appropriate supportive care as needed.

Nonclinical Toxicology

Pregnancy Category C indicates that 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 during 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 studies conducted with rats, the administration of NSAIDs, including ibuprofen, has been associated with an increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown.

No specific details regarding animal pharmacology and toxicology beyond the effects noted in the nonclinical toxicology section are available.

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, potentially due to factors such as fluid retention, occult or gross gastrointestinal blood loss, or an incompletely described 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 present with any signs or symptoms of anemia.

Reports indicate that NSAIDs may reduce the antihypertensive effect of ACE inhibitors, warranting consideration in patients who are concurrently taking these medications. While several short-term controlled studies did not demonstrate a significant effect of ibuprofen tablets on prothrombin times or various clotting factors in individuals on coumarin-type anticoagulants, caution is advised. Bleeding events have been reported in patients receiving ibuprofen tablets alongside anticoagulants, and the combined use of warfarin and NSAIDs has been associated with an increased risk of serious gastrointestinal bleeding compared to the use of either drug alone.

Patient Counseling

Patients should be informed of essential information before initiating therapy with ibuprofen tablets 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 discuss the potential for serious cardiovascular (CV) side effects associated with ibuprofen, including myocardial infarction (MI) and stroke, which may lead to hospitalization or death. Patients should be made aware that serious CV events can occur without warning symptoms. They should be instructed to remain vigilant for signs and symptoms such as chest pain, shortness of breath, weakness, or slurring of speech, and to seek medical advice if they observe any of these indicative signs.

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

Healthcare providers should make patients aware of the risk of serious skin side effects associated with ibuprofen, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may also lead to hospitalization or death. Patients should be instructed to monitor for signs and symptoms such as skin rash, blisters, fever, or other hypersensitivity reactions like itching. They should be advised to discontinue the medication immediately and contact their physician if any rash develops.

Patients should be encouraged to promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider. Additionally, they should be informed about the warning signs of hepatotoxicity, including nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms. If these occur, patients should be instructed to stop 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 they experience these symptoms.

Finally, it is crucial to inform patients 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 various package configurations, with specific NDC numbers available for identification. It is essential to store the product at a controlled room temperature, maintaining a range of 20° to 25°C (68° to 77°F), in accordance with USP guidelines. Proper storage conditions are crucial to ensure the integrity and efficacy of the product.

Additional Clinical Information

Patients on long-term treatment with ibuprofen should have their complete blood count (CBC) and chemistry profile monitored periodically. If any clinical signs or symptoms indicative of liver or renal disease arise, or if systemic manifestations such as eosinophilia or rash occur, ibuprofen should be discontinued, especially if abnormal liver tests persist or worsen.

Before initiating therapy with ibuprofen, patients should be counseled on potential serious cardiovascular risks, including myocardial infarction (MI) and stroke, and advised to recognize symptoms such as chest pain and shortness of breath. They should also be aware of gastrointestinal risks, including ulcers and bleeding, and report any signs of these conditions, such as epigastric pain or melena. Additionally, patients should be informed about the risk of serious skin reactions, including exfoliative dermatitis and Stevens-Johnson syndrome (SJS), and should discontinue the medication and seek medical attention if a rash develops. Other important counseling points include reporting unexplained weight gain or edema, recognizing signs of hepatotoxicity, and being aware of anaphylactoid reactions. Finally, ibuprofen should be avoided in late pregnancy due to the risk of premature closure of the ductus arteriosus.

FDA Insert (PDF)

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

View full prescribing information (PDF)