Ibuprofen

Description

Ibuprofen tablets 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 tablets are available in strengths of 400 mg, 600 mg, and 800 mg for oral administration. Inactive ingredients include silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycols, polyvinyl alcohol, pregelatinized starch, talc, and titanium dioxide.

Uses and Indications

Ibuprofen tablets are indicated for the relief of the signs and symptoms associated with rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in pediatric populations have not been conducted. Therefore, caution is advised when considering the use of this medication in children.

Dosage and Administration

The lowest effective dose of ibuprofen tablets should be utilized for the shortest duration consistent with individual patient treatment goals. After assessing the response to initial therapy, healthcare professionals should adjust the dose and frequency to meet the specific needs of each patient.

The total daily dose must not exceed 3200 mg. In cases where gastrointestinal complaints arise, it is advisable to administer ibuprofen tablets with meals or milk to mitigate these effects.

For the management of rheumatoid arthritis and osteoarthritis, the suggested dosage ranges from 1200 mg to 3200 mg daily, which 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 important to tailor the dose to each patient, with adjustments made based on the severity of symptoms. Generally, patients with rheumatoid arthritis may require higher doses compared to those with osteoarthritis.

For mild to moderate pain, a dosage of 400 mg may be given every 4 to 6 hours as needed for pain relief. In the case of dysmenorrhea, a dosage of 400 mg every 4 hours may be administered as necessary for pain relief. The smallest effective dose that provides acceptable control should always be employed.

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), as severe and potentially fatal anaphylactic-like reactions have been reported in these patients. Furthermore, ibuprofen tablets are contraindicated in the context of 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 ibuprofen use. These events can be fatal and may occur early in treatment, with the risk potentially increasing with prolonged use. Ibuprofen is contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

There is also an elevated risk of serious gastrointestinal adverse events, such as bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These gastrointestinal events may occur at any time during treatment and often without warning symptoms. Elderly patients are particularly at greater risk for these serious gastrointestinal complications.

Anaphylactoid reactions may occur in patients who have not previously been exposed to ibuprofen. In such cases, it is imperative to seek emergency medical assistance immediately. Additionally, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can occur and may be fatal. Patients should discontinue ibuprofen at the first sign of a skin rash or any other indication of hypersensitivity. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has also been reported and can be life-threatening; ibuprofen should be discontinued if any signs or symptoms of DRESS are present.

Ibuprofen is not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of the underlying disease. Furthermore, the pharmacological effects of ibuprofen in reducing fever and inflammation may mask diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions.

Monitoring for signs or symptoms of gastrointestinal bleeding is essential, as serious gastrointestinal tract ulcerations and bleeding can occur without warning. Patients on long-term NSAID therapy should have their complete blood count (CBC) and chemistry profile assessed periodically. If any clinical signs or symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, ibuprofen should be discontinued.

In cases of anaphylactoid reactions, immediate emergency medical help is necessary. Patients should also discontinue ibuprofen tablets if they experience any signs or symptoms of DRESS and seek immediate evaluation. Furthermore, ibuprofen should be stopped at the first appearance of a skin rash or any other sign of hypersensitivity.

Side Effects

Patients receiving treatment with this medication 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. The risk of these events may increase with the duration of use and can occur early in treatment. Additionally, there is an increased risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal events can occur at any time during use and without warning symptoms, with elderly patients being at greater risk.

Gastrointestinal reactions are common and may include nausea, epigastric pain, heartburn, diarrhea, abdominal distress, vomiting, indigestion, constipation, and abdominal cramps or pain. More severe gastrointestinal issues such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis have also been reported.

Central nervous system effects may manifest as dizziness, headache, and nervousness, with more serious reactions including depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Other reported symptoms include paresthesias, hallucinations, dream abnormalities, and pseudo-tumor cerebri.

Dermatologic reactions can range from common rashes, including maculopapular types and pruritis, to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, and photoallergic skin reactions.

Adverse reactions affecting special senses include tinnitus, hearing loss, amblyopia (blurred and/or diminished vision), conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic reactions may include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, and decreases in hemoglobin and hematocrit. Bleeding episodes, such as epistaxis and menorrhagia, have also been reported.

Metabolic and endocrine reactions can include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

Cardiovascular reactions may involve edema, fluid retention (which generally responds promptly to drug discontinuation), congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (including sinus tachycardia and sinus bradycardia).

Allergic reactions can present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Other allergic conditions reported include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal adverse reactions may include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria, and renal papillary necrosis.

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

Postmarketing experience has revealed additional serious skin and appendage reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and fixed drug eruption.

Drug Interactions

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and various other medications may lead to significant drug interactions that require careful consideration.

Antihypertensive Agents NSAIDs may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors when used together. Clinicians should monitor blood pressure and consider dosage adjustments of the antihypertensive agent as necessary.

Antiplatelet Agents Ibuprofen can interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered prior to aspirin. For patients taking low-dose aspirin for cardiovascular protection, it is advisable to select NSAIDs that do not affect aspirin's efficacy or to consider non-NSAID analgesics. The concomitant use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

Diuretics Ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics, which necessitates close monitoring for signs of renal failure in patients receiving these combinations.

Lithium The use of 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 receiving this combination.

Methotrexate NSAIDs may enhance the toxicity of methotrexate by competitively inhibiting its renal accumulation. Caution is advised when these agents are used together, and monitoring for signs of methotrexate toxicity should be implemented.

Anticoagulants Caution is warranted when administering ibuprofen to patients on warfarin-type anticoagulants due to the increased risk of serious gastrointestinal bleeding. Regular monitoring of coagulation parameters is recommended.

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

Overall, healthcare providers should remain vigilant for potential interactions and adjust treatment regimens accordingly to ensure patient safety.

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 closely monitor this population for potential adverse effects and to consider appropriate dosage adjustments based on individual patient needs and responses.

Pregnancy

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy is associated with significant risks, particularly when used after approximately 20 weeks of gestation. The use of NSAIDs at about 30 weeks gestation or later increases the risk of premature closure of the fetal ductus arteriosus, which can lead to serious fetal complications. Additionally, NSAID use during this period has been linked to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment.

Healthcare professionals are advised to limit the dose and duration of ibuprofen tablets use between approximately 20 and 30 weeks of gestation. If NSAID treatment is deemed necessary after 20 weeks, it should be restricted to the lowest effective dose for the shortest duration possible. If treatment extends beyond 48 hours, monitoring with ultrasound for oligohydramnios is recommended. Should oligohydramnios be detected, ibuprofen tablets should be discontinued, and follow-up should be conducted according to clinical practice guidelines.

Data from observational studies regarding the potential embryofetal risks of NSAID use in the first and second trimesters are inconclusive. While reproductive studies in rats and rabbits have not shown evidence of developmental abnormalities, animal reproduction studies are not always predictive of human outcomes. Furthermore, animal data suggest that prostaglandins play a crucial role in endometrial vascular permeability, blastocyst implantation, and fetal kidney development. Inhibition of prostaglandin synthesis by NSAIDs like ibuprofen has been associated with increased pre- and post-implantation loss and impaired kidney development at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2-4% and 15-20%, respectively. However, the specific background risk associated with ibuprofen tablets remains unknown. There are no adequate, well-controlled studies in pregnant women, and ibuprofen tablets should only be used during pregnancy if the potential benefits justify the potential risks to the fetus.

Published literature indicates that adverse outcomes, such as fetal renal dysfunction leading to oligohydramnios, may occur after days to weeks of NSAID treatment, although some cases of oligohydramnios have been reported as soon as 48 hours after initiation. In many instances, the decrease in amniotic fluid was transient and reversible upon cessation 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.

It is important to note that methodological limitations in postmarketing studies, including the lack of control groups and limited information on dose, duration, and timing of drug exposure, hinder the establishment of a reliable estimate of the risk of adverse fetal and neonatal outcomes associated with maternal NSAID use. Additionally, the safety data primarily involve preterm infants, raising uncertainty about the generalizability of reported risks to full-term infants exposed to NSAIDs through maternal use.

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; therefore, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, subsequently, renal blood flow. This can precipitate overt renal decompensation, particularly in patients at greatest risk, including 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. However, there is no information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease, and 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.

Additionally, the use of NSAIDs, including ibuprofen tablets, during pregnancy, particularly around 20 weeks gestation or later, may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes can occur after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after initiation. If NSAID treatment is required between 20 and 30 weeks of gestation, it is recommended to limit ibuprofen tablets to the lowest effective dose and shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if treatment extends beyond 48 hours, and ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up according to clinical practice.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a critical role in maintaining renal perfusion. In patients with compromised liver function, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate renal decompensation.

Patients at the highest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. Therefore, it is crucial to exercise caution when considering NSAID therapy in this population.

Currently, there is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Consequently, treatment with ibuprofen tablets is not recommended for these patients. If the initiation of ibuprofen tablet therapy is deemed necessary, close monitoring of renal function is advised to mitigate potential risks. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of careful patient management.

Overdosage

In cases of ibuprofen overdosage, symptoms can vary significantly based on the amount ingested and the age and weight of the individual.

Clinical Presentation Severe overdose symptoms have been observed in a 19-month-old child who ingested 7 to 10 ibuprofen tablets (400 mg), resulting in apneic and cyanotic episodes approximately 1½ hours post-ingestion. Blood levels of ibuprofen in this case were measured at 102.9 µg/mL approximately 8½ hours after ingestion. Conversely, in two separate cases involving children weighing around 10 kg who ingested approximately 120 mg/kg of ibuprofen, no acute intoxication symptoms were noted.

In adults, a 19-year-old male who consumed 8,000 mg of ibuprofen over a few hours experienced dizziness but ultimately recovered following hospitalization and supportive care.

Management of Overdosage For effective management of acute ibuprofen overdosage, it is crucial to empty the stomach by inducing vomiting or performing gastric lavage within 1 hour of ingestion. This intervention is most effective when administered promptly after the overdose.

Additionally, the administration of oral activated charcoal may be beneficial in reducing both the absorption and reabsorption of ibuprofen tablets in overdose situations. Given the acidic nature of ibuprofen, administering alkali and inducing diuresis may also provide therapeutic advantages.

Healthcare professionals should remain vigilant for the potential symptoms of ibuprofen overdosage and implement appropriate management strategies to mitigate risks and support patient 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 increases the risk of premature closure of the fetal ductus arteriosus. Additionally, the use of these medications from approximately 20 weeks gestation onward 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 shown that the administration of prostaglandin synthesis inhibitors, such as ibuprofen, can result in increased pre- and post-implantation loss. 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.

Due to the risk of premature closure of the fetal ductus arteriosus, the use of NSAIDs, including ibuprofen tablets, is advised against in pregnant women at approximately 30 weeks gestation and later. If NSAID treatment is deemed necessary between 20 and 30 weeks gestation, it is recommended to limit the use of ibuprofen tablets to the lowest effective dose for the shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if treatment with ibuprofen tablets extends beyond 48 hours. In cases of oligohydramnios, discontinuation of ibuprofen tablets is advised, with follow-up according to clinical practice.

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. In rat studies involving NSAIDs, similar to other drugs that 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 remain unknown.

Postmarketing Experience

During postapproval use of ibuprofen, the following adverse reactions have been identified through voluntary reports and surveillance programs: exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE). These events were reported in the context of pharmacovigilance and are included for informational purposes.

Patient Counseling

Patients should be informed of the symptoms associated with cardiovascular thrombotic events, which include chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to report any of these symptoms to their healthcare provider immediately.

It is important to communicate that ibuprofen tablets 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 alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should seek medical advice upon observing any indicative signs or symptoms.

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

Additionally, patients should be vigilant for symptoms of congestive heart failure, which may include shortness of breath, unexplained weight gain, or edema. They should be instructed to contact their healthcare provider if such symptoms occur.

It is essential to inform patients 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.

Patients should also be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. In the event of these symptoms, patients should be instructed to seek immediate emergency help.

Pregnant women should be advised to avoid the use of ibuprofen tablets and other NSAIDs starting at 30 weeks 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 gestation, she should be informed that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

Storage and Handling

The product is supplied in well-closed containers to ensure integrity and stability. It should be stored at a temperature range of 20 ° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the quality and efficacy of the product.

Additional Clinical Information

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as there is a risk of serious GI tract ulcerations and bleeding associated with the use of ibuprofen. For patients undergoing long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that complete blood counts (CBC) and chemistry profiles be checked periodically to assess for potential adverse effects.

In cases where patients exhibit clinical signs and symptoms indicative of liver or renal disease, or if systemic manifestations such as eosinophilia or rash occur, ibuprofen tablets should be discontinued. Additionally, if abnormal liver tests persist or worsen, immediate cessation of the medication is advised.

FDA Insert (PDF)

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

View full prescribing information (PDF)