Ibuprofen

Description

Ibuprofen tablets USP contain the active ingredient ibuprofen, which is chemically defined as (±) - 2 - (p - isobutylphenyl) propionic acid. Ibuprofen appears as a white to off-white crystalline powder with a melting point ranging from 74 to 77°C. It exhibits high solubility in alcohol, methanol, acetone, and chloroform, while being slightly soluble in ethyl acetate and practically insoluble in water. The structural formula of ibuprofen is provided below.

These tablets are classified as a nonsteroidal anti-inflammatory drug (NSAID) and are available in dosages of 400 mg, 600 mg, and 800 mg for oral administration. The formulation includes several inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol-partially hydrolyzed, povidone, stearic acid, talc, and 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

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

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

For the management of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage ranges from 1200 mg to 3200 mg daily. This can be administered as 300 mg four times a day (qid) or as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). It is important to tailor the dose to each patient, adjusting it based on the severity of symptoms at the initiation of therapy or in response to treatment outcomes. Generally, patients with rheumatoid arthritis may require higher doses compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should always be employed.

For the treatment of mild to moderate pain, ibuprofen tablets may be given 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 administered 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. Additionally, the use of ibuprofen is not recommended for individuals who have a history of asthma, urticaria, or other 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 documented in these patients. Furthermore, ibuprofen tablets are contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Nonsteroidal 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.

NSAIDs can also lead to severe gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which may be fatal. These serious adverse events can occur at any time, with or without warning symptoms. Patients with a history of peptic ulcer disease and/or gastrointestinal bleeding are at more than a tenfold increased risk of developing a GI bleed when using NSAIDs compared to those without these risk factors.

Anaphylactoid reactions may occur in individuals without prior exposure to ibuprofen tablets. In such cases, emergency medical assistance should be sought immediately. Additionally, NSAIDs, including ibuprofen, can cause serious skin adverse reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs and symptoms of serious skin reactions and advised to discontinue ibuprofen tablets at the first appearance of a skin rash or any other indication of hypersensitivity.

The use of NSAIDs, including ibuprofen tablets, is not recommended for pregnant women at approximately 30 weeks gestation and later 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 disease. For patients on prolonged corticosteroid therapy, a gradual tapering of the corticosteroid dosage is advised if discontinuation is necessary.

The pharmacological effects of ibuprofen tablets in reducing fever and inflammation may obscure diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions.

For patients undergoing long-term treatment with NSAIDs, including ibuprofen tablets, it is recommended to monitor hemoglobin or hematocrit levels if any signs or symptoms of anemia are present. Additionally, patients who may be adversely affected by changes in platelet function, such as those with coagulation disorders or those receiving anticoagulants, should be closely monitored.

Emergency medical help should be sought in cases of anaphylactoid reactions. Patients are advised to discontinue ibuprofen tablets at the first sign of a skin rash or any other indication of hypersensitivity. If serious gastrointestinal events are suspected, the NSAID should be discontinued until a serious GI adverse event is ruled out.

Side Effects

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

Serious adverse reactions include cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. The risk of these events may arise early in treatment and is known to increase with prolonged use. Additionally, there is a significant 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 treatment and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Common gastrointestinal reactions reported include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal issues may involve nausea and vomiting, indigestion, constipation, abdominal cramps or pain, and a sensation of fullness in the gastrointestinal tract, such as bloating and flatulence. More severe gastrointestinal complications, 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 observed.

Central nervous system reactions may include dizziness, headache, and nervousness, with more serious effects such as 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 rash (including maculopapular types) and pruritus to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, and photoallergic skin reactions.

In the realm of special senses, tinnitus, hearing loss, amblyopia (blurred and/or diminished vision), conjunctivitis, diplopia, optic neuritis, and cataracts have been reported.

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

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

Cardiovascular reactions can include edema and fluid retention, which generally respond promptly to drug discontinuation. Other cardiovascular issues may involve congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (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 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 reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and fixed drug eruption.

Drug Interactions

Patients with asthma may exhibit aspirin-sensitive asthma, a condition where the administration of aspirin can lead to severe bronchospasm, potentially resulting in fatal outcomes. Consequently, the use of aspirin in these patients is contraindicated.

In addition, there is a noted cross-reactivity between aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen. Therefore, ibuprofen tablets should not be administered to patients with aspirin-sensitive asthma. Caution is advised when prescribing ibuprofen to patients with preexisting asthma, as bronchospasm may occur.

Patients receiving ibuprofen tablets should be monitored for visual disturbances, including blurred vision, diminished vision, scotomata, and changes in color vision. Should any of these symptoms arise, ibuprofen should be discontinued immediately, and an ophthalmologic examination is recommended. This examination should include assessments of central visual fields and color vision to evaluate any potential ocular effects.

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

There is no pediatric use information available for this medication, including recommended ages, dosing differences, safety concerns, or special precautions for children. Healthcare professionals should exercise caution when considering the use of this medication in pediatric patients due to the absence of relevant data.

Geriatric Use

Elderly patients may not have specific information regarding the use of this medication, including dosage adjustments, safety concerns, or special precautions. Therefore, healthcare providers should exercise caution when prescribing this medication to geriatric patients. It is advisable to monitor these patients closely for any potential adverse effects or changes in efficacy, given the lack of targeted data for this population.

Pregnancy

Pregnant women are advised to avoid the use of ibuprofen tablets and other nonsteroidal anti-inflammatory drugs (NSAIDs) starting at 30 weeks of gestation due to the risk of premature closure of the fetal ductus arteriosus, which can lead to significant fetal complications.

If treatment with ibuprofen tablets is deemed necessary for a pregnant woman between approximately 20 to 30 weeks of gestation, it is recommended that she be monitored for oligohydramnios if the treatment extends beyond 48 hours. This precaution is essential to ensure fetal well-being and to mitigate potential adverse outcomes associated with prolonged NSAID use during this critical period of pregnancy.

Lactation

There is no specific information available regarding the use of this medication in lactating mothers or its effects on breastfed infants. Healthcare professionals should consider the absence of data when advising lactating mothers about the use of this medication.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. In patients with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow, potentially precipitating overt renal decompensation. Patients at the highest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Typically, discontinuation of NSAID therapy results in recovery to the pretreatment state.

There is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease; therefore, treatment with ibuprofen tablets is not recommended in this population. If therapy with ibuprofen tablets is deemed necessary, close monitoring of 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 reported as early as 48 hours after initiation of NSAID therapy. While oligohydramnios is often reversible upon discontinuation of treatment, prolonged oligohydramnios can lead to complications such as limb contractures and delayed lung maturation.

If NSAID treatment is necessary between approximately 20 weeks 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 extends beyond 48 hours, and ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up conducted 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 with compromised renal function. In patients with hepatic dysfunction, the administration of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate renal decompensation.

Due to the lack of controlled clinical studies evaluating the use of ibuprofen tablets in patients with advanced renal disease, treatment with ibuprofen is not recommended for these individuals. If therapy with ibuprofen tablets is deemed necessary, it is essential to closely monitor renal function throughout the treatment period.

Patients with hepatic impairment should be assessed for their overall health status, including renal function, as those at greatest risk for adverse reactions include individuals 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, underscoring the importance of careful monitoring and consideration of alternative therapies in this patient population.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the time elapsed since ingestion.

Clinical Presentation

A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg each). Approximately 1½ hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli. Despite this, the painful stimulus was sufficient to induce respiration. Initial management included the administration of oxygen and parenteral fluids, with a greenish-yellow fluid aspirated from the stomach showing no evidence of ibuprofen. Two hours after ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced apnea lasting 5 to 10 seconds. Following admission to intensive care, sodium bicarbonate, dextrose, and normal saline infusions were administered. By four hours post-ingestion, the child was more alert, able to sit independently, and responsive to verbal commands. A blood level of ibuprofen measured 102.9 mcg/mL approximately 8½ hours after ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional cases involving children weighing approximately 10 kg who accidentally ingested about 120 mg/kg of ibuprofen, no signs of acute intoxication or late sequelae were observed. One child had a blood level of 700 mcg/mL 90 minutes after ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

A separate case involved a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours. He reported dizziness, and nystagmus was observed. After hospitalization, he received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

Management Recommendations

In instances of acute ibuprofen overdosage, it is recommended to empty the stomach through vomiting or gastric lavage; however, it should be noted that minimal drug recovery is expected if more than one hour has passed since ingestion. Given the acidic nature of ibuprofen and its urinary excretion, administering alkali and inducing diuresis may be beneficial. Supportive measures should be prioritized, and the use of oral activated charcoal may assist in reducing both absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant for potential symptoms and manage accordingly to ensure patient safety and recovery.

Nonclinical Toxicology

Taking nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy, particularly after approximately 20 weeks, may pose risks to the developing fetus. It is advised that NSAIDs not be used after around 30 weeks of gestation due to potential harm to the unborn child.

In rare instances, patients undergoing ibuprofen therapy have experienced aseptic meningitis, accompanied by fever and coma. This adverse effect highlights the need for careful monitoring during treatment.

No additional specific data regarding nonclinical toxicology or animal pharmacology and toxicology is available.

Postmarketing Experience

During postapproval use of ibuprofen, the following adverse reactions have been identified. These reactions have been reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and appendages-related adverse reactions include exfoliative dermatitis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID and periodically throughout the course of ongoing therapy. It is important to encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients to be alert for symptoms of cardiovascular thrombotic events, which may include 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.

Patients should be made aware that ibuprofen tablets, like other NSAIDs, can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects such as ulcers and bleeding, which may lead to hospitalization or even death. Although serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms, patients should be vigilant for signs and symptoms of ulcerations and bleeding. They should seek medical advice if they experience any indicative signs, including epigastric pain, dyspepsia, melena, or hematemesis.

Patients should be advised to stop taking ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible. Additionally, they should be alert for symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and should 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 symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should also be informed of the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat. In such cases, 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 various package configurations, with specific NDC numbers available for identification. 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. Care should be taken to avoid exposure to excessive heat, specifically temperatures exceeding 40°C (104°F). Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Anemia may occur in patients receiving NSAIDs, including ibuprofen tablets, potentially due to fluid retention, gastrointestinal blood loss, or effects on erythropoiesis. Clinicians should monitor hemoglobin or hematocrit levels in patients on long-term NSAID therapy who exhibit signs of anemia. In postmarketing studies, a decrease in hemoglobin of 1 gram or more was noted in 17.1% of patients taking 1600 mg daily for osteoarthritis and in 22.8% of those taking 2400 mg daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were reported.

NSAIDs, including ibuprofen, inhibit platelet aggregation and may prolong bleeding time, although their effect is less significant and reversible compared to aspirin. Patients with coagulation disorders or those on anticoagulants should be closely monitored for any adverse effects related to alterations in platelet function.

FDA Insert (PDF)

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

View full prescribing information (PDF)