Ibuprofen

Description

Ibuprofen tablets contain the active ingredient ibuprofen, which is chemically defined as (±) - 2 - (p - isobutylphenyl) propionic acid. Ibuprofen appears as a white powder with a melting point of 74-77°C. It is characterized by very slight solubility in water (less than 1 mg/mL) and is readily soluble in organic solvents such as ethanol and acetone. The structural formula of ibuprofen is represented below.

This nonsteroidal anti-inflammatory drug (NSAID) is formulated for oral administration and is available in tablet strengths of 400 mg, 600 mg, and 800 mg. The tablets also contain several inactive ingredients, including carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, polysorbate, 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

For the treatment 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 400 mg, 600 mg, or 800 mg taken three to four times daily (tid or qid). Individual patient responses may vary, with some patients potentially benefiting from a higher dosage of 3200 mg daily compared to 2400 mg. It is essential to tailor the dosage to each patient, adjusting based on the severity of symptoms.

For the management of mild to moderate pain, a dosage of 400 mg may be taken every 4 to 6 hours as needed for pain relief.

In cases of dysmenorrhea, a dosage of 400 mg is recommended every 4 hours as necessary for pain relief.

Healthcare professionals should ensure that the total daily dose does not exceed 3200 mg. In instances where gastrointestinal complaints arise, it is advisable to administer ibuprofen tablets with meals or milk to mitigate these effects.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, 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.

Furthermore, ibuprofen tablets are contraindicated for the treatment of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery. Caution is also advised when considering ibuprofen for patients with preexisting asthma, particularly those with aspirin-sensitive asthma.

Warnings and Precautions

Cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, may occur with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen, and these events can be fatal. The risk of such events may increase with the duration of NSAID use. Ibuprofen is contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs are also associated with serious gastrointestinal (GI) adverse events, including bleeding, ulceration, and perforation, which can be fatal. These events can occur at any time during treatment and may present without warning symptoms. Patients with a recent MI should avoid Ibuprofen unless the potential benefits outweigh the risks of recurrent cardiovascular thrombotic events. Additionally, NSAIDs can lead to new-onset hypertension or exacerbate preexisting hypertension; therefore, blood pressure should be monitored closely. The use of Ibuprofen may increase the risk of heart failure and edema, necessitating careful monitoring for signs of worsening heart failure.

Serious skin adverse events, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), can occur without prior warning. It is imperative to discontinue Ibuprofen at the first appearance of a skin rash or any signs of hypersensitivity. Anaphylactoid reactions may also occur; in such cases, emergency medical assistance should be sought immediately. In late pregnancy, Ibuprofen should be avoided due to the risk of premature closure of the ductus arteriosus.

Patients on prolonged corticosteroid therapy should taper their corticosteroids slowly if discontinuing treatment. Liver function tests should be monitored, as significant elevations may occur in some patients. For those on long-term NSAID treatment, hemoglobin or hematocrit levels should be checked periodically to assess for signs of anemia. Patients with asthma should be monitored for potential bronchospasm, and Ibuprofen should be avoided in individuals with aspirin-sensitive asthma. If patients experience blurred vision or changes in color vision, Ibuprofen should be discontinued, and an ophthalmologic examination should be conducted.

For patients on long-term NSAID treatment, it is essential to monitor for signs or symptoms of GI bleeding. Periodic checks of complete blood count (CBC) and chemistry profiles are recommended. Ibuprofen should be discontinued if clinical signs of liver or renal disease develop, or if abnormal liver tests persist or worsen.

Emergency medical help should be sought in cases of anaphylactoid reactions. Patients should also discontinue Ibuprofen and contact their healthcare provider if they experience signs of liver dysfunction or serious skin 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 cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. The risk of these events may increase with the duration of treatment and can occur early in the course of therapy. 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 may occur at any time during treatment and without warning symptoms, with elderly patients being 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 fullness of 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 noted in some patients.

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, and alopecia.

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, 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, as well as anaphylaxis and bronchospasm. Other allergic conditions reported include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal adverse reactions may include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria, and renal papillary necrosis. Miscellaneous reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

Patients should be monitored for these adverse reactions, and any serious or concerning symptoms should be reported to a healthcare provider promptly.

Drug Interactions

Concomitant use of certain medications with ibuprofen may lead to significant drug interactions, which can affect therapeutic outcomes and patient safety. The following interactions have been identified:

Pharmacodynamic Interactions

ACE-Inhibitors Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may reduce the antihypertensive effect of ACE-inhibitors. Clinicians should consider this interaction when prescribing NSAIDs to patients who are concurrently taking ACE-inhibitors.

Aspirin Pharmacodynamic studies indicate that ibuprofen can interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered before aspirin. This interaction is evident even with a once-daily regimen of ibuprofen at 400 mg. To mitigate this risk, it is advisable to administer immediate-release low-dose aspirin at least 2 hours prior to ibuprofen. However, this timing does not apply to enteric-coated low-dose aspirin. Given the potential for increased cardiovascular events due to this interaction, alternative analgesics that do not affect aspirin's antiplatelet effect should be considered for patients using low-dose aspirin for cardioprotection.

Warfarin-Type Anticoagulants While short-term studies have not shown significant effects of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, caution is warranted. The concomitant use of ibuprofen and anticoagulants may increase the risk of serious gastrointestinal bleeding, as the effects of both drugs on bleeding risk are synergistic.

Pharmacokinetic Interactions

Diuretics Ibuprofen may diminish the natriuretic effect of diuretics such as furosemide and thiazides, likely due to the inhibition of renal prostaglandin synthesis. Patients receiving both ibuprofen and diuretics should be closely monitored for signs of renal failure and to ensure the efficacy of the diuretic therapy.

Lithium Concomitant administration of ibuprofen has been shown to elevate plasma lithium levels and decrease renal clearance of lithium. Specifically, a study indicated a 15% increase in mean minimum lithium concentration and a 19% reduction in renal clearance. Careful monitoring for signs of lithium toxicity is recommended when these medications are used together.

Methotrexate NSAIDs, including ibuprofen, may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is advised when administering NSAIDs alongside methotrexate.

Other Interactions

H-2 Antagonists Studies involving cimetidine or ranitidine co-administered with ibuprofen have shown no significant impact on ibuprofen serum concentrations, indicating that these H-2 antagonists do not alter the pharmacokinetics of ibuprofen.

In summary, careful consideration and monitoring are essential when ibuprofen is prescribed alongside these medications to mitigate potential adverse effects and ensure therapeutic efficacy.

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 this medication in children. Further studies are needed to determine appropriate dosing and outcomes in this population.

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

Pregnant patients should be aware that ibuprofen is classified as a Pregnancy Category C medication. Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women, and ibuprofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, particularly the closure of the ductus arteriosus, the use of ibuprofen during late pregnancy should be avoided. Additionally, studies in rats have indicated that NSAIDs, including ibuprofen, may lead to an increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of ibuprofen on labor and delivery in pregnant women remain unknown. Therefore, healthcare professionals should carefully consider the risks and benefits when prescribing ibuprofen to pregnant patients.

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. The administration of NSAIDs in these individuals may lead to a dose-dependent reduction in prostaglandin formation, subsequently decreasing renal blood flow and potentially precipitating overt renal decompensation.

Patients at greatest risk for these adverse effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy typically 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 the patient's renal function is advised.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs, including Ibuprofen tablets. 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 NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate renal decompensation.

Patients at heightened risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. 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 this population. 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.

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) and presented to the emergency department approximately 1½ hours post-ingestion. The child was apneic and cyanotic, responding only to painful stimuli, which was sufficient to induce respiration. Initial management included the administration of oxygen and parenteral fluids. Gastric aspiration yielded a greenish-yellow fluid, with no evidence of ibuprofen detected. Two hours after ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced intermittent 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 μg/mL approximately 8½ hours after ingestion, and the child appeared to have fully recovered by the 12-hour mark.

In two additional cases involving children weighing approximately 10 kg who ingested about 120 mg/kg of ibuprofen, no signs of acute intoxication or late sequelae were observed. One child exhibited a blood level of 700 μg/mL 90 minutes post-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 presented with dizziness and nystagmus. 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 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 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 each case based on the clinical presentation and the specific circumstances surrounding the overdosage event.

Nonclinical Toxicology

Pregnancy Category C indicates that reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, it is important to note that animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Therefore, ibuprofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, specifically the closure of the ductus arteriosus, the use of ibuprofen during late pregnancy should be avoided.

Postmarketing Experience

In two postmarketing clinical studies, a greater incidence of decreased hemoglobin levels was reported than previously documented. Specifically, a decrease in hemoglobin of 1 gram or more was observed in 17.1% of 193 patients receiving 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients taking 2400 mg of ibuprofen daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were noted in these studies.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, are known to inhibit platelet aggregation and may prolong bleeding time in some patients. While their effect on platelet function is quantitatively less, of shorter duration, and reversible compared to aspirin, patients who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or those receiving anticoagulants, should be monitored closely.

Reports indicate that NSAIDs may reduce the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors, which should be considered in patients taking both medications concurrently.

Several short-term controlled studies have not demonstrated a significant effect of ibuprofen on prothrombin times or other clotting factors in individuals on coumarin-type anticoagulants. However, bleeding events have been reported in patients taking ibuprofen and other NSAIDs alongside coumarin-type anticoagulants. Therefore, caution is advised when administering ibuprofen to patients on anticoagulants, as the combined use of warfarin and NSAIDs may increase the risk of serious gastrointestinal bleeding compared to either drug used alone.

Aseptic meningitis, accompanied by fever and coma, has been observed on rare occasions in patients undergoing ibuprofen therapy. This condition appears to be more likely in patients with systemic lupus erythematosus and related connective tissue diseases, although it has also been reported in individuals without underlying chronic diseases. If signs or symptoms of meningitis develop in a patient receiving ibuprofen, the potential association with ibuprofen should be evaluated.

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. They should be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients to be 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.

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 alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should be apprised of the importance of seeking medical advice upon observing any indicative signs or symptoms.

It is also crucial to inform patients that ibuprofen tablets can lead to serious skin side effects, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Patients should be alert for signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity, such as itching. They should be advised to discontinue the medication immediately if any type of rash develops and to contact their physician as soon as possible.

Healthcare providers should instruct patients to be aware of 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 also 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.

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

Finally, it is important to inform patients that ibuprofen tablets should be avoided in late pregnancy, as with other NSAIDs, due to the risk of causing premature closure of the ductus arteriosus.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product at room temperature, maintaining a temperature range of 15-30°C. Proper storage conditions are crucial to ensure the integrity and efficacy of the product.

Additional Clinical Information

Physicians are advised to monitor patients on long-term treatment with NSAIDs for signs or symptoms of gastrointestinal (GI) bleeding. Additionally, it is recommended that these patients undergo periodic checks of their complete blood count (CBC) and chemistry profile to ensure ongoing safety and efficacy of the treatment.

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. Furthermore, 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 AiPing Pharmaceutical, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)