Ibuprofen

Description

Ibuprofen tablets USP contain the active ingredient ibuprofen, which is (±) - 2 - (p - isobutylphenyl) propionic acid. Ibuprofen is characterized 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 is represented 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 inactive ingredients such as 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 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.

For 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 daily (qid) or as 400 mg, 600 mg, or 800 mg three to four times daily (tid or qid). The dose should be tailored to each patient, with adjustments made based on the severity of symptoms at the time of initiating therapy or in response to treatment. It is noted that patients with rheumatoid arthritis may require higher doses compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should be employed.

In cases of mild to moderate pain, ibuprofen tablets may be administered at a dose of 400 mg every 4 to 6 hours as necessary for pain relief. For the treatment of dysmenorrhea, ibuprofen tablets should be given at a dose of 400 mg every 4 hours, starting with the earliest onset of pain.

After observing the response to initial therapy, the dose and frequency should be adjusted to meet individual patient needs. It is important not to exceed a total daily dose of 3200 mg. If gastrointestinal complaints occur, ibuprofen tablets should be administered with meals or milk. A therapeutic response is often observed within a few days to a week, but most commonly by two weeks. Following a satisfactory response, the patient's dose should be reviewed and adjusted as necessary.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Use is also contraindicated in individuals who have a history of asthma, urticaria, or allergic-type reactions following the administration of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been reported in these patients. Additionally, ibuprofen tablets should not be administered 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. It is crucial to note that ibuprofen tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs are also linked to severe gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can 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, it is imperative to seek emergency medical assistance immediately. Additionally, NSAIDs can lead to serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can also be fatal. Patients should discontinue ibuprofen tablets at the first sign of a skin rash or any other indication of hypersensitivity.

Pregnant women, particularly those at approximately 30 weeks gestation and later, should avoid the use of NSAIDs, including ibuprofen tablets, due to the risk of premature closure of the fetal ductus arteriosus.

It is important to recognize that 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 long-term NSAID therapy, including ibuprofen tablets, monitoring of hemoglobin or hematocrit levels is recommended if any signs or symptoms of anemia are present. Furthermore, 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 during treatment.

In the event of an anaphylactoid reaction, emergency medical help should be sought immediately. Patients are advised to discontinue ibuprofen tablets at the first appearance of a skin rash or any other sign of hypersensitivity and to contact their healthcare provider promptly.

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 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 may occur at any time during treatment and without warning symptoms, with elderly patients being at greater risk.

Gastrointestinal adverse 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 reactions may manifest as dizziness, headache, and nervousness. Other reported symptoms include depression, insomnia, confusion, emotional liability, somnolence, and in rare cases, aseptic meningitis with fever and coma. Patients may also experience 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.

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 may involve decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

Cardiovascular reactions can include 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 (sinus tachycardia and sinus bradycardia).

Allergic reactions may present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting; anaphylaxis; bronchospasm; 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 noted cases of 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. Therefore, 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. Consequently, 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, or changes in color vision. If any of these symptoms develop, 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 damage.

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

No pediatric use information is provided in the text. Therefore, there are no relevant age ranges, dosage differences, study outcomes, or cautions to report regarding the use of this medication in pediatric patients.

Geriatric Use

There is no specific information regarding the use of this medication in geriatric patients, including dosage adjustments, safety concerns, or special precautions. Healthcare providers should exercise caution when prescribing this medication to elderly patients, as they may have altered pharmacokinetics and pharmacodynamics. Close monitoring is recommended to ensure safety and efficacy in 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 mitigate potential risks to fetal 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, which can precipitate 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 initiation of ibuprofen tablet therapy 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 manifest after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours after NSAID initiation. 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. Ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up conducted according to clinical practice guidelines.

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 compensatory role in maintaining renal perfusion. In patients with compromised liver function, 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 study data regarding 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 at greatest risk for adverse reactions include 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.

Overdosage

Approximately 1½ hours following the ingestion of 7 to 10 ibuprofen tablets (400 mg) by a 19-month-old child weighing 12 kg, the child presented to the hospital emergency room in a state of apnea and cyanosis, responding only to painful stimuli. This stimulus was sufficient to induce respiration. Upon examination, oxygen and parenteral fluids were administered, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen presence. Two hours post-ingestion, the child's condition appeared stable; however, she continued to respond solely to painful stimuli and experienced intermittent apnea lasting 5 to 10 seconds. The child was subsequently admitted to intensive care, where sodium bicarbonate, along with infusions of dextrose and normal saline, was administered. By four hours after ingestion, the child could be easily aroused, sit independently, and respond to verbal commands. A blood level of ibuprofen measured 102.9 mcg/mL approximately 8½ hours post-ingestion, and by 12 hours, the child showed complete recovery.

In two additional reported cases involving children, each weighing approximately 10 kg, accidental acute ingestion of approximately 120 mg/kg of ibuprofen resulted in no signs of acute intoxication or late sequelae. Notably, one child's blood level was recorded at 700 mcg/mL 90 minutes after ingestion, which is approximately ten times the peak levels observed in absorption-excretion studies.

A case involving a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours presented with dizziness, and nystagmus was noted. Following hospitalization, the patient received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

In instances of acute overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage; however, it is important to note 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 theoretically beneficial. Supportive measures should be implemented, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

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, indicating a serious adverse effect associated with this medication.

No additional specific data regarding nonclinical toxicology or animal pharmacology and toxicology are 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 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 for patients to be alert for signs and symptoms of gastrointestinal ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis. Patients should seek medical advice upon observing any indicative signs or symptoms.

Patients should be instructed 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.

Healthcare providers should inform patients to be vigilant for symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms occur.

Patients should be made aware of the warning signs and symptoms of hepatotoxicity, which may include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms. They should be instructed to stop therapy and seek immediate medical attention if these symptoms arise.

Patients should also be informed about the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat, and should be instructed to seek immediate emergency help if these symptoms occur.

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 closing 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 accordance with the following specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance 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 shorter in duration compared to aspirin. Patients with coagulation disorders or those on anticoagulants should be closely monitored for potential alterations in platelet function.

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)