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 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 is represented below.

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 inactive ingredients such as 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

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

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

For the management of rheumatoid arthritis and osteoarthritis, 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). The dosage should be tailored to each patient, with adjustments made based on the severity of symptoms at the initiation of therapy or in response to treatment.

It is noted that patients with rheumatoid arthritis may require higher doses of ibuprofen tablets compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should be utilized, as a linear blood level dose-response relationship exists with single doses up to 800 mg.

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

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of ibuprofen tablets 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). 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 may be fatal and is particularly pronounced in patients with existing CV disease or risk factors. It is imperative to use the lowest effective dose 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 concurrent use of aspirin reduces the risk of serious CV thrombotic events linked to NSAID use.

NSAIDs have the potential to induce new hypertension or exacerbate preexisting hypertension. Therefore, it is essential to monitor blood pressure closely during NSAID therapy.

Patients taking NSAIDs may experience fluid retention and edema, necessitating caution in those with a history of fluid retention or congestive heart failure.

The gastrointestinal (GI) effects of NSAIDs warrant significant attention, as they can lead to serious adverse events such as inflammation, bleeding, ulceration, and perforation, which may be fatal. These events can occur unexpectedly, with or without warning symptoms. Patients with a history of ulcer disease or gastrointestinal bleeding are at more than a tenfold increased risk for developing GI bleeding. Both patients and healthcare providers should remain vigilant for signs and symptoms of GI ulcerations and bleeding during NSAID treatment, and prompt evaluation and intervention should be initiated if a serious GI event is suspected.

Long-term use of NSAIDs has been associated with renal injury, particularly in patients with impaired renal function, heart failure, liver dysfunction, those on diuretics or ACE inhibitors, and the elderly. Discontinuation of NSAID therapy typically leads to recovery of renal function. In patients with advanced renal disease, the use of ibuprofen tablets is not recommended; if treatment is deemed necessary, close monitoring of renal function is advised.

Anaphylactoid reactions may occur in patients without prior exposure to NSAIDs. In such cases, immediate emergency medical assistance should be sought. Additionally, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can occur. The use of the drug should be discontinued at the first sign of a skin rash or any indication of hypersensitivity.

During late pregnancy, the use of ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus. Patients should be instructed to discontinue use and contact their healthcare provider at the first appearance of a skin rash or any other sign of hypersensitivity. Emergency medical help should be sought in cases of anaphylactoid reactions.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication, categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular events such as myocardial infarction, stroke, and other thrombotic events, which can be fatal. The risk of these events may increase with the duration of use, particularly in patients with pre-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 symptoms. Elderly patients are at a heightened risk for these gastrointestinal events. Additionally, renal effects such as acute renal failure and renal papillary necrosis may arise from long-term administration.

Common gastrointestinal adverse reactions reported include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal symptoms may include vomiting, indigestion, constipation, and bloating. More severe gastrointestinal issues, such as gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis, have also been observed.

Central nervous system reactions may manifest as dizziness, headache, and nervousness. More serious effects can include depression, insomnia, confusion, and emotional liability. Rarely, aseptic meningitis, hallucinations, and pseudo-tumor cerebri have been reported.

Dermatologic reactions range from common rashes and pruritus to more severe conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and alopecia. Patients may also experience vesiculobullous eruptions and photoallergic skin reactions.

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

Hematologic adverse reactions may include neutropenia, agranulocytosis, and thrombocytopenia, with some patients experiencing bleeding episodes. Metabolic and endocrine reactions can involve decreased appetite, gynecomastia, and hypoglycemic reactions.

Cardiovascular effects may present as edema, fluid retention, elevated blood pressure, and arrhythmias. Allergic reactions can range from mild symptoms to anaphylaxis, bronchospasm, and serum sickness.

Renal adverse reactions include decreased creatinine clearance, polyuria, and hematuria. Miscellaneous reactions may involve dry eyes and mouth, gingival ulcers, and rhinitis.

It is important to note that anaphylactoid reactions can occur in patients without prior exposure to the medication, and serious skin reactions such as exfoliative dermatitis and toxic epidermal necrolysis may arise unexpectedly.

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 already receiving ACE-inhibitors.

• Diuretics: Ibuprofen may diminish the natriuretic effect of diuretics such as furosemide and thiazides, likely due to the inhibition of renal prostaglandin synthesis. Patients on concomitant therapy should be closely monitored for signs of renal failure and to ensure the efficacy of diuretics.

• Warfarin-type Anticoagulants: While short-term studies have not shown significant effects of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of ibuprofen and anticoagulants may lead to a higher risk of serious gastrointestinal bleeding. Caution is advised when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

• Aspirin: Co-administration of ibuprofen with aspirin may reduce the protein binding of aspirin, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction remains unclear, but the concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

• Lithium: Ibuprofen has been shown to elevate plasma lithium levels and decrease renal clearance of lithium. In a study, the mean minimum lithium concentration increased by 15%, and renal clearance decreased by 19% during concurrent administration. Patients receiving both ibuprofen and lithium should be monitored closely for signs of lithium toxicity.

• Methotrexate: NSAIDs, including ibuprofen, may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is warranted when administering NSAIDs alongside methotrexate.

H-2 Antagonists: Studies indicate that the co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine does not significantly affect ibuprofen serum concentrations, suggesting 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

Safety and effectiveness of ibuprofen tablets in pediatric patients have not been established. Therefore, healthcare professionals should exercise caution 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. In cases where NSAID therapy is necessary, close monitoring of renal function is advisable. 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 for these patients.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no established 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

Approximately 1 ½ hours following the ingestion of 7 to 10 ibuprofen tablets (400 mg), a 19-month-old child weighing 12 kg 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 stabilized, although 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 dextrose and normal saline infusions, was administered. By four hours after 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 ½ hours post-ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional 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 reported dizziness, with nystagmus noted during examination. Following hospitalization, the patient received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

In instances of acute ibuprofen overdosage, it is recommended that the stomach be emptied 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 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. Ibuprofen tablets are classified as Pregnancy Category C, indicating that there are no adequate and well-controlled studies in pregnant women. Therefore, ibuprofen 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 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.

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 understood effect on erythropoiesis. It is recommended that patients on long-term NSAID treatment, including ibuprofen tablets, have their hemoglobin or hematocrit levels monitored if they exhibit any signs or symptoms of anemia.

NSAIDs are known to inhibit platelet aggregation and may prolong bleeding time in some patients. While their effect on platelet function is quantitatively less, of shorter duration, and reversible compared to aspirin, patients receiving ibuprofen tablets who may be adversely affected by changes in platelet function—such as those with coagulation disorders or those on anticoagulants—should be closely monitored.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been associated with NSAIDs, including ibuprofen tablets. These serious events can occur without warning. Patients should be informed of the signs and symptoms of serious skin reactions, and the use of ibuprofen should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity.

Aseptic meningitis, accompanied by fever and coma, has been observed on rare occasions in patients undergoing ibuprofen therapy. Although 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. If signs or symptoms of meningitis develop in a patient taking ibuprofen tablets, the potential association with the medication should be considered.

Patient Counseling

Patients should be informed of essential information before initiating therapy with ibuprofen tablets 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 tablets, 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 such as chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to seek medical advice immediately upon noticing any of these symptoms and understand the importance of follow-up regarding cardiovascular health.

Additionally, patients should be informed that ibuprofen tablets 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 complications can occur without warning symptoms; therefore, patients should be alert for signs of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should be instructed to seek medical advice if they experience any of these symptoms and understand the significance of monitoring for GI-related issues.

Patients should also be made aware of the potential for serious skin side effects associated with ibuprofen tablets, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Although serious skin reactions can 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.

It is important for patients to promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider. They should also be informed about the warning signs 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 be educated on the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat, and should be instructed to seek emergency help if these symptoms arise.

Finally, patients should be advised that ibuprofen tablets should be avoided during late pregnancy, as with other NSAIDs, due to the risk of 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 controlled room temperature of 20° to 25°C (68° to 77°F) to maintain its efficacy and stability. Care should be taken to ensure that the product is kept in a suitable container that protects it from environmental factors. Special handling requirements should be observed to prevent exposure to extreme temperatures or conditions that may compromise the product's integrity.

Additional Clinical Information

Patients undergoing long-term treatment with NSAIDs, including Ibuprofen Tablets, USP, should have their complete blood count (CBC) and chemistry profile monitored periodically. If any clinical signs indicative of liver or renal disease arise, or if systemic manifestations such as eosinophilia or rash occur, or if abnormal liver tests persist or worsen, discontinuation of the medication is advised.

Before initiating therapy with an NSAID, patients should be counseled on potential serious cardiovascular risks, including myocardial infarction and stroke, and should be vigilant for symptoms such as chest pain and shortness of breath. Additionally, patients should be aware of gastrointestinal risks, including ulcers and bleeding, and report any signs of these conditions, such as epigastric pain or melena. Serious skin reactions, including exfoliative dermatitis and Stevens-Johnson syndrome, warrant immediate medical attention if symptoms like rash or blisters develop. Patients should also report any unexplained weight gain or edema, and be informed about hepatotoxicity signs, such as jaundice or fatigue, which require prompt cessation of therapy. Anaphylactoid reactions, characterized by difficulty breathing or facial swelling, necessitate immediate emergency assistance. Furthermore, 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 Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)