Ibuprofen

Description

Ibuprofen tablets contain the active ingredient ibuprofen, chemically designated as (±)-2-(p-isobutylphenyl) propionic acid. Ibuprofen is a white powder with a melting point of 74-77°C, exhibiting very slight solubility in water (less than 1 mg/mL) while being 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 colloidal silicon dioxide, croscarmellose sodium, hypromellose 2910, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, pregelatinized starch, povidone k-90, sodium lauryl sulfate, 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 each 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, including flare-ups of chronic disease, the suggested dosage ranges from 1200 mg to 3200 mg daily. This can be achieved through various dosing schedules, such as 300 mg four times a day or 400 mg, 600 mg, or 800 mg three to four times a day. 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 always be employed.

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

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. They should not be administered to individuals who have experienced asthma, urticarial, or allergic-type reactions following the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been reported in these patients. Additionally, the use of ibuprofen tablets is contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Caution is advised when considering ibuprofen for patients with preexisting asthma, particularly those with aspirin-sensitive asthma.

Warnings and Precautions

Non-steroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen Tablets, are associated with an increased risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is likely to escalate with prolonged use. Ibuprofen Tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs can also lead to significant gastrointestinal (GI) adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which may be fatal. These events can occur at any time during treatment and may present without warning symptoms. Elderly patients are particularly vulnerable to serious GI complications. Therefore, it is essential to monitor patients for signs of GI bleeding, especially those on long-term NSAID therapy.

Clinical trials indicate that the risk of serious cardiovascular thrombotic events is consistent across all NSAIDs; however, patients with pre-existing cardiovascular disease or risk factors exhibit a higher absolute incidence of these events. Caution is advised when prescribing Ibuprofen Tablets to patients with a recent myocardial infarction, as the benefits must be weighed against the risk of recurrent cardiovascular thrombotic events. Continuous monitoring for signs of cardiac ischemia is recommended.

NSAIDs may also induce new hypertension or exacerbate existing hypertension. Blood pressure should be closely monitored during the initiation of NSAID treatment and throughout the duration of therapy. Additionally, the use of Ibuprofen Tablets in patients with severe heart failure should be approached with caution, as the potential for worsening heart failure must be considered. Patients should be monitored for signs of heart failure deterioration.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported with NSAID use. Discontinuation of Ibuprofen Tablets is warranted at the first sign of a skin rash or any indication of hypersensitivity. In late pregnancy, the use of Ibuprofen Tablets should be avoided due to the risk of premature closure of the ductus arteriosus.

Ibuprofen Tablets are not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. For patients on prolonged corticosteroid therapy, a gradual tapering of corticosteroids is recommended if discontinuation is necessary. Patients receiving long-term NSAID treatment should have their hemoglobin or hematocrit levels monitored if they exhibit any signs or symptoms of anemia. Additionally, those who may be adversely affected by changes in platelet function should be closely observed.

Patients with asthma who have aspirin-sensitive asthma should not be administered Ibuprofen Tablets due to the risk of exacerbating their condition.

Regular laboratory tests are advised for patients on long-term NSAID therapy. Physicians should monitor for signs or symptoms of GI bleeding and 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 the event of an anaphylactoid reaction, emergency medical assistance should be sought immediately. Patients should also discontinue Ibuprofen Tablets and contact their healthcare provider if they experience clinical signs and symptoms consistent with liver disease or systemic manifestations such as eosinophilia or rash.

Side Effects

Patients receiving treatment with non-steroidal anti-inflammatory drugs (NSAIDs) may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is known to increase with prolonged use. Additionally, NSAIDs are associated with a heightened risk of serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal complications can occur at any time during therapy and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Common gastrointestinal adverse reactions reported in clinical trials include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal issues such as constipation, abdominal cramps, and bloating have also been noted. Serious gastrointestinal complications, including gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis, have been observed.

Central nervous system reactions may include dizziness, headache, and nervousness, with more serious effects such as depression, insomnia, confusion, and somnolence reported. Rarely, aseptic meningitis with fever and coma has been documented. Patients may also experience paresthesias, hallucinations, and dream abnormalities.

Dermatologic reactions can range from mild rashes and pruritus to severe conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Other skin reactions include vesiculobullous eruptions and photoallergic skin reactions.

Adverse reactions affecting special senses include tinnitus, hearing loss, and amblyopia, with potential for more serious conditions such as optic neuritis and cataracts.

Hematologic adverse reactions may involve neutropenia, agranulocytosis, and thrombocytopenia, with bleeding episodes such as epistaxis and menorrhagia also reported.

Metabolic and endocrine reactions include decreased appetite, gynecomastia, and hypoglycemic reactions. Cardiovascular effects may manifest as edema, fluid retention, congestive heart failure in patients with marginal cardiac function, elevated blood pressure, and arrhythmias.

Allergic reactions can present as a syndrome of abdominal pain, fever, chills, and anaphylaxis, along with conditions such as serum sickness and angioedema. Renal adverse reactions include acute renal failure, decreased creatinine clearance, and hematuria.

Miscellaneous reactions reported include dry eyes and mouth, gingival ulcers, and rhinitis.

In clinical trials, the incidence of reported side effects was higher at doses of 3200 mg/day compared to doses of 2400 mg or less, although the increases were slight and remained within the ranges previously documented. Reactions occurring in 3% to 9% of patients treated with ibuprofen are marked, while those occurring in less than 3% are unmarked. Adverse reactions are classified under “Probable Causal Relationship (PCR)” if there has been a positive rechallenge or if three or more cases occur that might be causally related. Conversely, reactions are classified as having a “Causal Relationship Unknown” if seven or more events have been reported but do not meet the criteria for PCR.

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 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 should be monitored closely for signs of lithium toxicity when these medications are used together.

• 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 no clinically relevant interaction.

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

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 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

Pregnant patients should be aware that this medication is classified as 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, this medication should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is important to note that nonsteroidal anti-inflammatory drugs (NSAIDs) have known effects on the fetal cardiovascular system, particularly concerning the closure of the ductus arteriosus. Consequently, the use of this medication during late pregnancy should be avoided to minimize potential risks to fetal outcomes. Healthcare professionals are advised to carefully consider the risks and benefits when prescribing this medication to women of childbearing potential and 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 with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion. The administration of an NSAID in these individuals may lead to a dose-dependent reduction in prostaglandin formation, subsequently decreasing renal blood flow and potentially precipitating overt renal decompensation.

Patients at greatest risk for these adverse effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. 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 ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's renal function is advised.

Hepatic Impairment

Patients with hepatic impairment may experience altered drug metabolism and clearance, necessitating caution when using ibuprofen tablets. It is recommended that liver function tests be monitored periodically in this patient population to assess any changes in liver status.

In cases of significant liver impairment, a reduced dose of ibuprofen tablets should be considered to minimize the risk of adverse effects. If liver function tests indicate significant deterioration, it is advised to discontinue the use of ibuprofen tablets to ensure patient safety.

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 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. Initial management included the administration of oxygen and parenteral fluids, alongside 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 mcg/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 mcg/mL 90 minutes post-ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

Management of Overdosage For acute ibuprofen overdosage, it is recommended to empty the stomach through vomiting or gastric lavage; however, this is most effective if performed within one hour of ingestion, as little drug is likely to be recovered thereafter. 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 can be considered to reduce both absorption and reabsorption of the drug.

A case involving a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours reported dizziness and exhibited nystagmus. After hospitalization, he received parenteral hydration and was placed on bed rest for three days, ultimately recovering without any reported sequelae.

In summary, while ibuprofen overdosage can lead to significant clinical symptoms, prompt medical intervention and supportive care can result in favorable outcomes.

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.

In studies involving rats, the administration of NSAIDs 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.

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.

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 that typically occurs in asthmatic patients who may experience rhinitis with or without nasal polyps, or who may exhibit severe, potentially fatal bronchospasm after taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, have been associated with NSAIDs, including ibuprofen tablets. These serious events may occur without warning.

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

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 advised to remain vigilant for symptoms of cardiovascular thrombotic events, which may include chest pain, shortness of breath, weakness, or slurring of speech. They should be instructed to report any of these symptoms to their healthcare provider immediately.

It is important to inform patients that ibuprofen tablets, like other NSAIDs, can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects such as ulcers and bleeding. These complications may lead to hospitalization and even death. Patients should be made aware that serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms. They should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they observe any indicative signs or symptoms.

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

Healthcare providers should counsel patients to be alert 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.

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

Additionally, patients should be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. They should be instructed to seek immediate emergency help if these symptoms arise.

Finally, it is crucial to inform patients 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 upon request. It should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), in accordance with USP Controlled Room Temperature guidelines. Care should be taken to avoid exposure to excessive heat, specifically temperatures exceeding 40ºC (104ºF). Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Physicians are advised to monitor patients on long-term treatment with NSAIDs for any signs or symptoms indicative of gastrointestinal bleeding. Additionally, it is recommended that these patients undergo periodic evaluations of their complete blood count (CBC) and chemistry profile to ensure ongoing safety and efficacy of the treatment.

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. Furthermore, 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 PharmPak, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)