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. 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 evaluate the potential benefits and risks of ibuprofen tablets alongside other treatment options prior to prescribing. It is recommended to use the lowest effective dose for the shortest duration that aligns with individual patient treatment goals.

After assessing the patient's response to initial therapy with ibuprofen tablets, the dosage 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 discomfort.

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 regimens, 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 individualized, with adjustments made based on the severity of symptoms at the initiation of therapy or in response to treatment outcomes. It is noted that patients with rheumatoid arthritis may require higher doses compared to those with osteoarthritis. The smallest effective dose that provides adequate symptom control should be utilized.

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 commence 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 may be fatal. This risk can manifest early in treatment and may 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 may occur at any time during treatment and often without warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal complications. Therefore, healthcare professionals should exercise caution and monitor patients closely.

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 Ibuprofen Tablets are administered in such cases, it is imperative to monitor for signs of cardiac ischemia.

NSAIDs, including Ibuprofen Tablets, may lead to the onset of new hypertension or exacerbate preexisting hypertension. Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the treatment duration. Additionally, the use of Ibuprofen Tablets in patients with severe heart failure should be approached with caution, as the benefits must outweigh the risks of worsening heart failure. Patients should be monitored for signs of deterioration in heart failure status.

Serious skin adverse events, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported with NSAID use and can be fatal. Patients should be informed of the signs and symptoms of serious skin reactions, and Ibuprofen Tablets should be discontinued at the first appearance of a rash or any other hypersensitivity signs. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has also been reported; if any signs or symptoms of DRESS occur, Ibuprofen Tablets should be discontinued immediately, and the patient should be evaluated.

The use of NSAIDs, including Ibuprofen Tablets, is contraindicated in pregnant women at approximately 30 weeks gestation and later due to the risk of premature closure of the fetal ductus arteriosus.

Patients on prolonged corticosteroid therapy should have their corticosteroids tapered slowly if discontinuation is necessary. Those exhibiting symptoms or signs of liver dysfunction, or 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.

For patients on long-term NSAID therapy, including Ibuprofen Tablets, it is recommended to periodically check hemoglobin or hematocrit levels, especially if any signs or symptoms of anemia are present. Additionally, patients who may be adversely affected by changes in platelet function should be closely monitored.

Healthcare professionals should monitor for signs or symptoms of gastrointestinal bleeding in patients receiving long-term NSAID treatment. Regular checks of complete blood count (CBC) and chemistry profiles are advised for these patients. If any clinical signs consistent with liver or renal disease develop, Ibuprofen Tablets should be discontinued.

Emergency medical assistance should be sought immediately in the event of an anaphylactoid reaction. Patients should be instructed to discontinue Ibuprofen Tablets and contact their healthcare provider if they experience clinical signs and symptoms indicative of liver disease or systemic manifestations such as eosinophilia or rash. The medication should also be stopped at the first sign of a skin rash or any other indication of hypersensitivity.

Side Effects

Patients may experience a range of adverse reactions while using the medication, categorized by seriousness and frequency.

Gastrointestinal adverse reactions are common and may 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 less frequent, can include gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis.

Central nervous system effects are also noted, with dizziness, headache, and nervousness being common. More serious reactions may include depression, insomnia, confusion, emotional liability, somnolence, and rare occurrences of aseptic meningitis, which can present with fever and coma. Other reported central nervous system effects include paresthesias, hallucinations, dream abnormalities, and pseudo-tumor cerebri.

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

Hematologic adverse reactions may include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), and thrombocytopenia with or without purpura. Patients may also experience eosinophilia and decreases in hemoglobin and hematocrit, along with bleeding episodes such as epistaxis and menorrhagia.

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

Cardiovascular reactions may include edema and fluid retention, which generally respond promptly to drug discontinuation. Other cardiovascular effects can include congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias such as sinus tachycardia and sinus bradycardia.

Allergic reactions may present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Additional allergic reactions can 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 ulcers, and rhinitis.

It is important to note that aseptic meningitis with fever and coma has been observed on rare occasions in patients undergoing ibuprofen therapy. Borderline elevations of liver tests may occur in up to 15% of patients taking NSAIDs, including ibuprofen tablets, with notable elevations of ALT or AST reported in approximately 1% of patients in clinical trials. Rare cases of severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some of which have resulted in fatal outcomes, have also been documented. Anaphylactoid reactions may occur in patients without known prior exposure to ibuprofen tablets, and these tablets should not be administered to patients with the aspirin triad.

Drug Interactions

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

Antihypertensive Agents NSAIDs, including ibuprofen, may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors. It is advisable to monitor blood pressure closely in patients receiving this combination.

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 for patients on low-dose aspirin therapy.

Diuretics The use of ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics. Close observation for signs of renal failure is recommended during concomitant therapy.

Lithium Ibuprofen has been shown to elevate plasma lithium levels and reduce renal clearance of lithium, which increases the risk of lithium toxicity. Monitoring of lithium levels is advised when these agents are used together.

Methotrexate NSAIDs may enhance the toxicity of methotrexate by competitively inhibiting its accumulation. Caution is warranted with concurrent use, and monitoring for signs of toxicity is recommended.

Anticoagulants Caution is also advised when administering ibuprofen to patients on warfarin-type anticoagulants due to an 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 appear to have a substantive effect on ibuprofen serum concentrations, indicating that no dosage adjustment is necessary for these agents.

Packaging & NDC

The table below lists all NDC Code configurations of Ibuprofen, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of ibuprofen tablets in pediatric patients have not been established. Therefore, caution should be exercised when considering the use of ibuprofen in this population. Further studies are needed to determine appropriate dosing and outcomes in children.

Geriatric Use

Caution should be exercised when treating elderly patients (65 years and older) with this medication, as with any nonsteroidal anti-inflammatory drugs (NSAIDs). It is important for healthcare providers to consider the increased risk of adverse effects in this population. Monitoring for potential side effects and adjusting dosages as necessary may be warranted to ensure the safety and efficacy of treatment in geriatric patients.

Pregnancy

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 many cases of decreased amniotic fluid were transient and reversible upon discontinuation of the drug, there have been reports of irreversible neonatal renal dysfunction requiring invasive interventions, such as exchange transfusion or dialysis.

At around 30 weeks of gestation or later, the use of NSAIDs significantly increases the risk of premature closure of the fetal ductus arteriosus. Therefore, it is recommended that ibuprofen tablets be avoided during this period. If NSAID treatment is deemed necessary after 20 weeks of gestation, it should be limited to the lowest effective dose for the shortest duration possible. Should treatment extend beyond 48 hours, monitoring with ultrasound for oligohydramnios is advised. If oligohydramnios is detected, ibuprofen tablets should be discontinued, and follow-up should be conducted according to clinical practice guidelines.

Data from observational studies regarding the risks of NSAID use during the first and second trimesters remain inconclusive. In the general U.S. population, the background rate of major malformations in clinically recognized pregnancies is 2-4%, with a pregnancy loss rate of 15-20%, regardless of drug exposure. Animal studies have not demonstrated developmental abnormalities with ibuprofen; however, these studies are not always predictive of human outcomes. There are no adequate and well-controlled studies in pregnant women, and ibuprofen should only be used during pregnancy if the potential benefits justify the potential risks to the fetus.

Prostaglandins play a crucial role in various reproductive processes, including endometrial vascular permeability and fetal kidney development. Animal studies have shown that the administration of prostaglandin synthesis inhibitors, such as ibuprofen, can lead to increased pre- and post-implantation loss and may impair kidney development at clinically relevant doses.

Given the potential risks associated with NSAID use during pregnancy, healthcare professionals should carefully evaluate the necessity of ibuprofen tablets and consider alternative therapies when appropriate.

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 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 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 available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease; therefore, treatment with ibuprofen tablets is not recommended in this population. If initiation of 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 NSAID initiation. If NSAID treatment is required between approximately 20 weeks and 30 weeks gestation, it is recommended to limit ibuprofen tablet use 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 require dosage adjustments to ensure safety and efficacy. It is essential to monitor liver function tests in these patients regularly to assess their liver status. Caution should be exercised when administering ibuprofen to individuals with compromised liver function. If there is any deterioration in liver function during treatment, ibuprofen should be discontinued immediately to prevent further complications.

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 signs of acute intoxication. Notably, one of these children had a blood level of 700 mcg/mL measured 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 several hours. He experienced dizziness but ultimately recovered following parenteral hydration and three days of bed rest.

For the management of acute ibuprofen overdosage, it is critical to empty the stomach by inducing vomiting or performing gastric lavage within one hour of ingestion, as little drug will likely be recovered after this period. 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.

Healthcare professionals should remain vigilant for symptoms of overdosage and implement appropriate management strategies promptly to mitigate potential complications.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy, particularly after approximately 30 weeks of gestation, has been associated with an increased risk of premature closure of the fetal ductus arteriosus. Observational studies regarding other potential embryo-fetal risks associated with NSAID use in women during the first or second trimesters of pregnancy have yielded inconclusive results. In the general U.S. population, the background rate of major malformations in clinically recognized pregnancies, irrespective of drug exposure, is estimated to be between 2-4%, with a pregnancy loss rate of 15-20%.

Animal reproductive studies conducted in rats and rabbits have not provided evidence of developmental abnormalities; however, it is important to note that animal reproduction studies may not always predict human responses. Prostaglandins play a critical role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has been linked to increased pre- and post-implantation loss.

The use of NSAIDs, including ibuprofen tablets, after approximately 20 weeks of gestation may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment. These adverse effects typically manifest after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours following the initiation of NSAID therapy. While oligohydramnios is often reversible upon discontinuation of treatment, prolonged oligohydramnios may lead to complications such as limb contractures and delayed lung maturation. In certain postmarketing cases of impaired neonatal renal function, invasive interventions, including exchange transfusion or dialysis, have been necessary.

Currently, there is no information available from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Consequently, the use of ibuprofen tablets is not recommended for these patients. If therapy with ibuprofen tablets is deemed necessary, close monitoring of the patient's renal function is advised.

In animal studies, the administration of prostaglandin synthesis inhibitors, including ibuprofen, has been associated with increased pre- and post-implantation loss. Prostaglandins are also recognized for their significant role in fetal kidney development, and published animal studies have indicated that prostaglandin synthesis inhibitors can impair kidney development when administered at clinically relevant doses.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with ibuprofen tablets, reported voluntarily or through surveillance programs. Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen, necessitating immediate medical attention in such cases. Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported and can be fatal, often occurring without warning.

Additionally, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been documented in patients using NSAIDs, including ibuprofen, with some cases resulting in fatal or life-threatening outcomes. In two postmarketing clinical studies, a higher incidence of decreased hemoglobin levels was observed than previously reported, with a decrease of 1 gram or more noted in 17.1% of 193 patients taking 1600 mg daily for osteoarthritis and in 22.8% of 189 patients taking 2400 mg daily for rheumatoid arthritis. Positive stool occult blood tests and elevated serum creatinine levels were also 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 within the first week of treatment. The incidence of death in the first year post-MI was reported at 20 per 100 person-years for NSAID-treated patients, compared to 12 per 100 person-years for those not exposed to NSAIDs. Some studies suggested that the heightened risk of serious cardiovascular thrombotic events may begin as early as the first weeks of treatment, particularly at higher doses.

Furthermore, reports indicate that NSAIDs may reduce the antihypertensive effect of ACE inhibitors. Clinical studies and postmarketing observations have also shown that ibuprofen tablets can diminish the natriuretic effect of furosemide and thiazides in certain patients.

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.

Healthcare providers should communicate that ibuprofen tablets may lead to serious cardiovascular side effects, such as myocardial infarction (MI) or stroke, potentially resulting in hospitalization or death. Patients must be vigilant for signs and symptoms of these events and seek medical advice if they experience any indicative symptoms.

It is important to inform patients that ibuprofen tablets can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, including ulcers and bleeding, which may also lead to hospitalization or death. Patients should be alert for signs of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis, and should contact their healthcare provider if they observe 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.

Healthcare providers should ensure that patients are aware of the symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and instruct them to contact their healthcare provider if such symptoms occur.

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

It is crucial to inform patients about the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. Patients should be instructed to seek immediate emergency help if these symptoms arise.

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 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 are advised to monitor patients for signs or symptoms of gastrointestinal (GI) bleeding during treatment. For patients undergoing long-term therapy 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 warranted.

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)