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 is available in 400 mg, 600 mg, and 800 mg tablets for oral administration. The inactive ingredients include colloidal silicon dioxide, croscarmellose sodium, hypromellose 2910, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, pregelatinized starch, povidone k-90, sodium lauryl sulphate, 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, healthcare professionals should exercise caution when considering the use of ibuprofen in children.

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 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 be utilized. In chronic conditions, a therapeutic response is often observed within a few days to a week, but is most commonly seen by two weeks. Once a satisfactory response is achieved, the patient's dosage should be reviewed and adjusted as necessary.

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 needed 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 necessary 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, urticaria, 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.

The use of NSAIDs is also linked to a heightened risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during treatment, often without warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal complications. Therefore, healthcare professionals should exercise caution and monitor patients closely for signs of gastrointestinal bleeding, especially in those on long-term NSAID therapy.

In patients with a recent myocardial infarction (MI), the use of Ibuprofen Tablets should be avoided unless the anticipated benefits outweigh the risks of recurrent cardiovascular thrombotic events. If treatment is deemed necessary, patients should be monitored for signs of cardiac ischemia. Additionally, NSAIDs can lead to new-onset hypertension or exacerbate preexisting hypertension; thus, blood pressure should be closely monitored during the initiation and throughout the course of NSAID therapy.

Patients with severe heart failure should avoid Ibuprofen Tablets unless the benefits are expected to outweigh the risks of worsening heart failure. If used, these patients should be monitored for signs of heart failure deterioration.

Anaphylactoid reactions may occur in patients without prior exposure to Ibuprofen Tablets, necessitating immediate emergency medical assistance in such cases. Furthermore, serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported and can be fatal. Patients should be informed to discontinue the medication at the first sign of a skin rash or any other hypersensitivity reaction.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has also been reported in patients taking NSAIDs like Ibuprofen Tablets. If any signs or symptoms indicative of DRESS occur, the medication should be discontinued, and the patient should be evaluated immediately.

Pregnant women at approximately 30 weeks gestation and later should avoid NSAIDs, including Ibuprofen Tablets, due to the risk of premature closure of the fetal ductus arteriosus.

Ibuprofen Tablets are 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 condition, and patients on prolonged corticosteroid therapy should have their medication tapered slowly if discontinuation is necessary.

Patients exhibiting symptoms or signs of liver dysfunction, or those with abnormal liver test results, should be evaluated for potential severe hepatic reactions while on Ibuprofen Tablets. If clinical signs consistent with liver disease develop, the medication should be discontinued. Additionally, patients who may be adversely affected by changes in platelet function, such as those with coagulation disorders or those receiving anticoagulants, should be monitored closely.

Healthcare professionals should routinely monitor patients on long-term NSAID therapy for signs or symptoms of gastrointestinal bleeding and periodically check complete blood count (CBC) and chemistry profiles. If any clinical signs or 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.

Patients should be educated on the signs and symptoms of serious cardiovascular events and instructed to seek immediate medical attention if they occur. Emergency medical help should also 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 an increased risk of 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, serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, can occur at any time during therapy and without warning symptoms. Elderly patients are particularly at heightened risk for these gastrointestinal complications. Renal effects, such as acute renal failure and renal papillary necrosis, have also been reported, particularly with long-term administration.

Other serious reactions may include anaphylactoid reactions, which can occur in patients without prior exposure to the medication, as well as severe skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, all of which can be fatal. Fetal toxicity is a concern, particularly in pregnant women at approximately 30 weeks gestation and later, due to the risk of premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios.

Common adverse reactions reported in clinical trials and postmarketing experiences include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Central nervous system effects may manifest as dizziness, headache, and nervousness, with more severe symptoms including depression, insomnia, and confusion. Dermatologic reactions can range from rash and pruritus to more severe conditions like urticaria and erythema multiforme.

Hematologic reactions such as neutropenia, agranulocytosis, and thrombocytopenia have been observed, alongside metabolic/endocrine effects like decreased appetite and gynecomastia. Cardiovascular reactions may include edema, fluid retention, and arrhythmias. Renal adverse reactions can involve decreased creatinine clearance and hematuria.

Miscellaneous reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis. It is essential for patients to be aware of these potential adverse reactions and to consult healthcare professionals if they experience any concerning symptoms.

Drug Interactions

The co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with various medications may lead to significant drug interactions that warrant careful consideration.

Antihypertensive Agents NSAIDs have the potential to diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors. Clinicians should monitor blood pressure closely when these agents are used concurrently.

Antiplatelet Agents Ibuprofen can interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered prior to aspirin. This interaction may increase the risk of cardiovascular events; therefore, alternative analgesics should be considered in patients requiring antiplatelet therapy.

Diuretics The use of ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics. Close monitoring for renal function is advised in patients receiving these combinations to prevent renal failure.

Lithium Ibuprofen has been shown to elevate plasma lithium levels and reduce its renal clearance, which increases the risk of lithium toxicity. Regular monitoring of lithium levels is recommended for patients taking both medications.

Methotrexate NSAIDs may enhance the toxicity of methotrexate. Caution is advised when these drugs are used together, and patients should be monitored for signs of toxicity.

Anticoagulants Co-administration of ibuprofen with warfarin-type anticoagulants may increase the risk of serious gastrointestinal bleeding. Clinicians should assess the need for dosage adjustments and monitor for signs of bleeding.

H2-Receptor Antagonists The co-administration of cimetidine or ranitidine with ibuprofen does not significantly affect ibuprofen serum concentrations, indicating that 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 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

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy is associated with specific risks that healthcare professionals should consider. The use of NSAIDs, particularly after approximately 20 weeks of gestation, has been linked to fetal renal dysfunction, which can lead to oligohydramnios and, in some instances, neonatal renal impairment. These adverse outcomes may occur after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours following NSAID initiation. While the decrease in amniotic fluid is often transient and reversible upon discontinuation of the drug, there are cases where neonatal renal dysfunction occurred without oligohydramnios, some of which were irreversible and required invasive interventions such as exchange transfusion or dialysis.

Healthcare professionals are advised to limit the use of ibuprofen tablets between approximately 20 and 30 weeks of gestation to the lowest effective dose for the shortest duration necessary. If treatment with ibuprofen tablets 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.

The use of NSAIDs at or after approximately 30 weeks of gestation is particularly concerning due to the increased risk of premature closure of the fetal ductus arteriosus. Therefore, NSAIDs should be avoided during this period.

Data from observational studies regarding the risks of NSAID use during the first and second trimesters of pregnancy remain inconclusive. In the general U.S. population, the background rate of major malformations is 2-4%, and the rate of pregnancy loss is 15-20%, regardless of drug exposure. Animal studies have not demonstrated developmental abnormalities with ibuprofen; however, animal reproduction studies are not always predictive of human outcomes. Prostaglandins play a crucial role in various aspects of pregnancy, including endometrial vascular permeability and fetal kidney development, and their inhibition by NSAIDs has been shown to impair kidney development in animal studies.

In summary, ibuprofen should only be used during pregnancy if the potential benefits outweigh the risks to the fetus, and careful consideration should be given to the timing and duration of 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 may 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 administration of an NSAID 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 therapy with ibuprofen tablets is deemed necessary, close monitoring of renal function is advised to mitigate the risk of renal complications. 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, clinical manifestations can vary significantly based on the amount ingested and the timing of intervention.

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 mcg/mL.

Conversely, two separate cases involving children weighing around 10 kg who ingested approximately 120 mg/kg of ibuprofen showed no acute signs of intoxication. Notably, one child's blood level was measured at 700 mcg/mL just 90 minutes after ingestion, indicating variability in individual responses to ibuprofen overdose.

In an adult case, a 19-year-old male consumed 8,000 mg of ibuprofen over several hours. He experienced dizziness but ultimately recovered following parenteral hydration and bed rest, with no lasting effects.

For the management of acute ibuprofen overdosage, it is critical to empty the stomach through vomiting or gastric lavage within one hour of ingestion, as little drug will likely be recovered after this period. The administration of alkali and the induction of diuresis may be advantageous due to the acidic nature of ibuprofen and its urinary excretion. Additionally, oral activated charcoal can be utilized to reduce further absorption of the drug.

Supportive measures are paramount in the management of ibuprofen overdose. Continuous monitoring for signs of toxicity is essential, and healthcare professionals should provide appropriate care based on the clinical presentation of the patient.

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 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 embryo-fetal risks associated with NSAID use during the first or second trimesters of pregnancy have yielded inconclusive results. In animal reproductive studies conducted in rats and rabbits, no evidence of developmental abnormalities was observed; however, it is important to note that animal reproduction studies may not always predict human responses.

Oligohydramnios, a condition that may arise from NSAID use, is often reversible upon discontinuation of treatment, although 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 were necessary.

There are no adequate and well-controlled studies in pregnant women regarding the use of ibuprofen. Therefore, it should be administered during pregnancy only if the potential benefits outweigh the potential risks to the fetus. Animal data indicate that prostaglandins play a crucial role in endometrial vascular permeability, blastocyst implantation, and decidualization. In studies involving animals, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has resulted in increased pre- and post-implantation loss. Furthermore, prostaglandins are essential for fetal kidney development, and published animal studies have reported that prostaglandin synthesis inhibitors can impair kidney development when given at clinically relevant doses.

In studies conducted with rats, NSAIDs, similar to other drugs that inhibit prostaglandin synthesis, have 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

Anaphylactoid reactions have been reported in patients without known prior exposure to ibuprofen tablets, necessitating emergency assistance in such cases. Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, have also been documented. These serious events may occur without warning.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been observed in patients taking NSAIDs, including ibuprofen tablets, with some cases being fatal or life-threatening. In two postmarketing clinical studies, a greater incidence of decreased hemoglobin levels was noted than previously reported, with a decrease of 1 gram or more observed in 17.1% of 193 patients on 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.

Observational studies from the Danish National Registry indicated that patients treated with NSAIDs in the post-myocardial infarction (MI) period faced an increased risk of reinfarction, cardiovascular-related death, and all-cause mortality, beginning in the first week of treatment. The incidence of death in the first year post-MI was reported at 20 per 100 person-years in NSAID-treated patients, compared to 12 per 100 person-years in those not exposed to NSAIDs. Some studies suggested that the increased risk of serious cardiovascular thrombotic events may begin as early as the first weeks of treatment, with this risk being most consistently observed at higher doses.

Reports indicate that NSAIDs may reduce the antihypertensive effect of ACE inhibitors. Clinical studies and postmarketing observations have shown that ibuprofen tablets can diminish the natriuretic effect of furosemide and thiazides in certain patients. Furthermore, the use of NSAIDs around 20 weeks of gestation or later in pregnancy has been associated with fetal renal dysfunction leading to oligohydramnios, and in some instances, neonatal renal impairment. Published studies and postmarketing reports corroborate these findings regarding maternal NSAID use during this period.

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, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately. It is important to communicate that ibuprofen tablets, like other NSAIDs, may cause serious cardiovascular side effects, such as myocardial infarction or stroke, which could lead to hospitalization or even death. Although serious cardiovascular events can occur without warning, patients should be alert for the aforementioned signs and symptoms and seek medical advice if they observe any indicative signs.

Additionally, patients should be made aware of the potential for gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, such as ulcers and bleeding, which may also result in hospitalization or death. Patients should be instructed to be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and to seek medical advice if they experience any of these 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. They should also be informed about the symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and instructed to contact their healthcare provider if such symptoms occur.

It is crucial 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 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 or swelling of the face or throat, and should be instructed to seek immediate emergency help if these symptoms arise.

Finally, healthcare providers should inform pregnant women 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 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 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

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)