Ibuprofen

Description

Ibuprofen tablets, USP contain the active ingredient ibuprofen, which is (±) - 2 - (p - isobutylphenyl) propionic acid. Ibuprofen is a white powder with a melting point of 74-77°C. It is very slightly soluble in water (<1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone. Ibuprofen is available in 400 mg, 600 mg, and 800 mg tablets for oral administration. Inactive ingredients include carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, and polysorbate, as well as 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

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, administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). Individual patient responses may vary, with some patients demonstrating a better response to a total daily dose of 3200 mg compared to 2400 mg. It is essential to tailor the dose to each patient, adjusting based on the severity of symptoms, while employing the smallest effective dose.

For the treatment of mild to moderate pain, a dosage of 400 mg may be administered every 4 to 6 hours as necessary for pain relief. In cases of dysmenorrhea, the recommended dosage is 400 mg every 4 hours as needed for pain relief.

Healthcare professionals should ensure that the total daily dose does not exceed 3200 mg. In instances where gastrointestinal complaints arise, it is advisable to administer ibuprofen tablets with meals or milk to mitigate these effects. After evaluating the patient's response to initial therapy, the dose and frequency should be adjusted to meet individual patient needs effectively.

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), as severe, potentially fatal, anaphylactic-like reactions have been reported in these patients. Furthermore, ibuprofen tablets are contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, has been associated with the use of NSAIDs. These events can be fatal; therefore, it is imperative to use the lowest effective dose for the shortest duration possible. Healthcare professionals should inform patients about the symptoms of serious cardiovascular events and the appropriate actions to take if they occur.

Patients who have undergone coronary artery bypass graft (CABG) surgery are at an increased risk of myocardial infarction and stroke when treated with NSAIDs postoperatively. Consequently, the use of NSAIDs is contraindicated in this patient population.

In the post-MI period, NSAID treatment is linked to an elevated risk of reinfarction, cardiovascular-related death, and all-cause mortality. It is essential to monitor these patients for signs of cardiac ischemia if NSAIDs are prescribed.

NSAIDs may lead to the development of new hypertension or exacerbate preexisting hypertension. Therefore, blood pressure should be monitored closely during NSAID therapy.

Patients with heart failure are at an increased risk of hospitalization and mortality when treated with NSAIDs. Monitoring for signs of worsening heart failure is recommended.

Serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation, can occur with NSAID use and may be fatal. Patients should be vigilant for signs and symptoms of gastrointestinal ulcerations and bleeding.

Long-term use of NSAIDs can result in renal injury, particularly in patients with impaired renal function, heart failure, liver dysfunction, and the elderly. Close monitoring of renal function is advised for these patients.

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

Patients should be advised to discontinue Ibuprofen tablets and contact their healthcare provider if they develop any type of rash or fever.

Hepatotoxicity is a potential risk associated with NSAID use. Patients should be informed of the warning signs and symptoms of hepatotoxicity, such as nausea, fatigue, and jaundice. If these symptoms occur, therapy should be stopped, and immediate medical attention should be sought.

Healthcare professionals should monitor patients for signs or symptoms of gastrointestinal bleeding. For those on long-term NSAID treatment, periodic checks of complete blood count (CBC) and chemistry profiles are recommended. If signs of liver or renal disease develop, Ibuprofen should be discontinued.

In cases of anaphylactoid reactions, such as difficulty breathing or swelling of the face or throat, patients should seek emergency medical help without delay.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication. The following sections categorize these reactions based on their seriousness and frequency.

Gastrointestinal adverse reactions are among the most commonly reported, with an incidence greater than 1% but less than 3%. These include nausea, epigastric pain, heartburn, diarrhea, abdominal distress, vomiting, indigestion, constipation, abdominal cramps or pain, and fullness of the gastrointestinal tract characterized by bloating and flatulence.

Serious gastrointestinal events, although occurring with a precise incidence of less than 1%, may include gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis.

Other adverse reactions with a precise incidence of less than 1% and a probable causal relationship include dizziness, headache, and nervousness affecting the central nervous system; rash (including maculopapular types) and pruritus in dermatologic manifestations; tinnitus in special senses; and hematologic issues such as neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, and eosinophilia. Metabolic and endocrine reactions may present as decreased appetite, while cardiovascular effects can include edema and fluid retention, which generally respond promptly to drug discontinuation. Allergic reactions may manifest as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Renal adverse reactions may include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, and hematuria. Miscellaneous reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

Additional adverse reactions of clinical significance, though with an unknown precise incidence, include central nervous system effects such as depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Dermatologic reactions may also be severe, including vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, and photoallergic skin reactions. Special senses may be affected by hearing loss, amblyopia (blurred and/or diminished vision, scotomata, and/or changes in color vision), conjunctivitis, diplopia, and optic neuritis, with cataracts also reported. Hematologic concerns may include bleeding episodes such as epistaxis and menorrhagia. Metabolic and endocrine reactions can involve gynecomastia, hypoglycemic reactions, and acidosis. Cardiovascular issues may present as congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (including sinus tachycardia and sinus bradycardia). Allergic reactions may also include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema. Renal complications may involve renal papillary necrosis. Miscellaneous severe reactions include anaphylactoid reactions, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).

Healthcare professionals should monitor patients for these adverse reactions and manage them appropriately.

Drug Interactions

Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors may diminish the antihypertensive effect of the latter. Therefore, monitoring of blood pressure is recommended when these medications are used together.

Ibuprofen, a common NSAID, has been shown to interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered prior to aspirin. This interaction may necessitate a review of the timing of administration to ensure optimal therapeutic effects.

When ibuprofen is co-administered with aspirin, there is a reduction in ibuprofen's protein binding; however, its clearance remains unchanged. This interaction should be considered when evaluating the overall pharmacokinetics of ibuprofen in patients taking both medications.

The natriuretic effect of diuretics such as furosemide and thiazides may be reduced by ibuprofen, which could lead to an increased risk of renal failure. Close monitoring of renal function is advised in patients receiving this combination.

Additionally, ibuprofen can elevate plasma lithium levels and decrease renal clearance of lithium, thereby increasing the risk of lithium toxicity. Regular monitoring of lithium levels is recommended for patients on this combination.

NSAIDs, including ibuprofen, may enhance the toxicity of methotrexate due to competitive inhibition of its accumulation. Caution should be exercised when these drugs are used concurrently, and monitoring for signs of methotrexate toxicity is advised.

In patients receiving warfarin-type anticoagulants, caution is warranted when administering ibuprofen due to an increased risk of gastrointestinal bleeding. Regular assessment of coagulation parameters is recommended to mitigate this risk.

Co-administration of cimetidine or ranitidine with ibuprofen does not significantly affect ibuprofen serum concentrations, and no dosage adjustments are necessary in this context.

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, 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

The use of Nonsteroidal Anti-inflammatory Drugs (NSAI Ds) during pregnancy is generally not recommended due to potential risks to the fetus. NSAI Ds are contraindicated in pregnancy, particularly during the third trimester, as their use may lead to fetal harm. Known risks include potential cardiovascular effects and renal impairment in the fetus.

Healthcare providers should be consulted regarding the use of NSAI Ds during pregnancy, as dosage modifications may be necessary based on individual circumstances. Pregnant women should be advised to avoid the use of NSAI Ds unless absolutely necessary and prescribed by a healthcare provider. It is essential to weigh the benefits against the potential risks when considering NSAI D therapy in pregnant patients.

Lactation

Lactating mothers should inform their healthcare provider about all medications they are taking, including prescription and over-the-counter medicines, vitamins, and herbal supplements. It is important to note that non-steroidal anti-inflammatory drugs (NSAIDs) and certain other medications may interact with each other, potentially leading to serious side effects. Therefore, lactating mothers are advised not to initiate any new medication without prior consultation with their healthcare provider.

Renal Impairment

Long-term administration of NSAIDs, including Ibuprofen, has been associated with renal papillary necrosis and other forms of renal injury. In patients with reduced kidney function, 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 can precipitate overt renal decompensation, particularly in patients at higher risk, such as those 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 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 is not recommended in this population. If therapy with Ibuprofen must be initiated, close monitoring of renal function is advised.

Clinical studies and post-marketing observations indicate that Ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients, attributed to the inhibition of renal prostaglandin synthesis. Patients receiving concomitant NSAID therapy should be closely monitored for signs of renal failure and to ensure the efficacy of diuretics.

Additionally, Ibuprofen has been shown to elevate plasma lithium levels and reduce renal lithium clearance. In a study involving normal volunteers, the mean minimum lithium concentration increased by 15%, while renal clearance decreased by 19% during concomitant administration. This effect is also linked to the inhibition of renal prostaglandin synthesis. Therefore, when Ibuprofen and lithium are used together, careful observation for signs of lithium toxicity is warranted.

Due to the potential for serious gastrointestinal tract ulcerations and bleeding, which can occur without warning symptoms, physicians should monitor patients for signs or symptoms of GI bleeding. Patients on long-term NSAID treatment should have their complete blood count (CBC) and chemistry profile checked periodically. If clinical signs and symptoms consistent with 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.

Hepatic Impairment

Patients with hepatic impairment may experience borderline elevations of one or more liver tests, which can occur in up to 15% of individuals taking NSAIDs, including Ibuprofen tablets. These laboratory abnormalities may progress, remain unchanged, or be transient with continued therapy. Notable elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST), defined as approximately three or more times the upper limit of normal, have been reported in about 1% of patients in clinical trials involving NSAIDs.

Severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, have been reported in rare cases, some of which have resulted in fatal outcomes. Therefore, patients presenting with symptoms and/or signs suggestive of liver dysfunction, or those with abnormal liver test values, should be closely evaluated for the potential development of more severe hepatic reactions while undergoing therapy with Ibuprofen tablets.

In the event that clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations such as eosinophilia or rash occur, Ibuprofen tablets should be discontinued immediately. Patients should be educated about the warning signs and symptoms of hepatotoxicity, which include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms. Should any of these symptoms arise, patients are advised to stop therapy and seek immediate medical attention.

If clinical signs and symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, discontinuation of Ibuprofen tablets is warranted. Regular monitoring of liver function is recommended for patients with compromised liver function to ensure timely intervention if abnormalities arise.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the patient's age and weight.

A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg). This child presented with apneic and cyanotic symptoms, necessitating oxygen and fluid administration. Blood analysis approximately 8½ hours post-ingestion revealed a concentration of 102.9 μg/mL.

Conversely, two separate cases involving children weighing approximately 10 kg who ingested about 120 mg/kg of ibuprofen showed no signs of acute intoxication. Notably, one child's blood level was measured at 700 μg/mL just 90 minutes after ingestion, indicating that significant variability in response can occur.

In an adult case, a 19-year-old male ingested 8,000 mg of ibuprofen over a few hours. He experienced dizziness but recovered fully after receiving hydration and bed rest, with no lasting effects.

Management of ibuprofen overdosage should be initiated promptly. In cases of acute overdosage, it is recommended to empty the stomach through vomiting or gastric lavage within one hour of ingestion, as little drug will likely be recovered after this time frame. The administration of oral activated charcoal may also be beneficial in reducing both absorption and reabsorption of ibuprofen.

Additionally, due to the acidic nature of ibuprofen, administering alkali and inducing diuresis may enhance urinary excretion of the drug, potentially mitigating its effects. Healthcare professionals should remain vigilant for symptoms and manage accordingly to ensure patient safety and recovery.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, during pregnancy has been associated with several teratogenic effects. Administration of NSAIDs around 30 weeks gestation or later may increase the risk of premature closure of the fetal ductus arteriosus. Additionally, the use of these medications at approximately 20 weeks gestation or later has been linked to fetal renal dysfunction, which can lead to oligohydramnios and, in some instances, neonatal renal impairment. Observational studies regarding other potential embryofetal risks associated with NSAID use during the first or second trimesters have yielded inconclusive results. Animal studies have demonstrated that the administration of prostaglandin synthesis inhibitors, such as Ibuprofen, can result in increased pre- and post-implantation loss. Furthermore, prostaglandins play a crucial role in fetal kidney development, and published animal studies indicate that prostaglandin synthesis inhibitors may impair kidney development when administered at clinically relevant doses.

Oligohydramnios, a condition that may arise from NSAID use, is often reversible upon discontinuation of treatment; however, complications from prolonged oligohydramnios can include limb contractures and delayed lung maturation. In certain postmarketing cases of impaired neonatal renal function, invasive interventions such as exchange transfusion or dialysis have been necessary.

Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, it is important to note that animal reproduction studies do not always predict human responses. The estimated background risk of major birth defects and miscarriage for the indicated population remains unknown, as all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2-4% and 15-20%, respectively.

In animal pharmacology and toxicology studies involving NSAIDs, including Ibuprofen, there has been an observed increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of Ibuprofen tablets on labor and delivery in pregnant women have not been established.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of Ibuprofen tablets. Reports of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been documented, with some cases resulting in fatal or life-threatening outcomes. DRESS typically presents with symptoms such as fever, rash, lymphadenopathy, and/or facial swelling, and may also involve hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Early signs of hypersensitivity, including fever or lymphadenopathy, may occur even in the absence of a rash; therefore, discontinuation of Ibuprofen tablets and immediate patient evaluation is recommended if such symptoms arise.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have also been reported. These events can occur without warning, and patients should be educated on recognizing the signs and symptoms of serious skin reactions. The use of Ibuprofen tablets should be discontinued at the first appearance of a skin rash or any other indication of hypersensitivity.

In two postmarketing clinical studies, a higher incidence of decreased hemoglobin levels was observed than previously reported. Specifically, a decrease of 1 gram or more in hemoglobin was noted in 17.1% of 193 patients taking 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients taking 2400 mg daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were recorded in these studies.

There are indications that NSAIDs, including Ibuprofen tablets, may reduce the antihypertensive effect of ACE-inhibitors, warranting caution in patients using both medications concurrently. Furthermore, while several short-term controlled studies did not demonstrate significant effects of Ibuprofen tablets on prothrombin times or other clotting factors in patients on coumarin-type anticoagulants, bleeding events have been reported. Physicians should exercise caution when prescribing Ibuprofen tablets to patients on anticoagulants, as the combined use of warfarin and NSAIDs may increase the risk of serious gastrointestinal bleeding.

Published studies and postmarketing reports have associated maternal NSAID use during pregnancy, particularly after 20 weeks gestation, with fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes typically manifest after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after initiation of NSAID therapy. In many instances, the reduction in amniotic fluid was transient and reversible upon discontinuation of the drug. However, there have been limited case reports of neonatal renal dysfunction occurring without oligohydramnios, some of which were irreversible and required invasive treatments such as exchange transfusion or dialysis.

Patient Counseling

Healthcare providers should advise patients to remain vigilant for symptoms indicative of cardiovascular thrombotic events, such as chest pain, shortness of breath, weakness, or slurring of speech. Patients 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 nonsteroidal anti-inflammatory drugs (NSAIDs), may cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, including ulcers and bleeding. These complications can lead to hospitalization and even death. Patients should be made aware of the signs and symptoms of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they experience any of these indicative signs.

Patients should be counseled to discontinue the use of Ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

Additionally, healthcare providers should inform 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 must be educated 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 any of these symptoms arise, patients should be instructed to stop therapy and seek immediate medical attention.

It is also crucial to inform patients about the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. Patients experiencing these symptoms should be advised to seek emergency help without delay.

For pregnant women, healthcare providers should recommend avoiding the use of Ibuprofen tablets and other NSAIDs starting at 30 weeks of gestation due to the risk of premature closure of the fetal ductus arteriosus. If treatment with Ibuprofen tablets is necessary for a pregnant woman between approximately 20 to 30 weeks of gestation, she should be advised that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

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, ensuring that the storage environment does not exceed 40°C (104°F) to maintain product integrity. Care should be taken to avoid exposure to excessive heat during storage and handling.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)