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 provided below.

These tablets are classified as a nonsteroidal anti-inflammatory drug (NSAID) and are formulated for oral administration in dosages of 400 mg, 600 mg, and 800 mg. The formulation includes several inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, 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

For the treatment of rheumatoid arthritis and osteoarthritis, 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). The total daily dose should not exceed 3200 mg. It is essential to tailor the dose 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, 400 mg can be administered every 4 hours as necessary for pain relief.

Administration of ibuprofen tablets should be done with meals or milk if gastrointestinal complaints arise. After evaluating the patient's response to the initial therapy, healthcare professionals should adjust the dose and frequency to meet individual patient needs. A therapeutic response may be observed within a few days to a week, but is most commonly seen by two weeks. Following a satisfactory response, it is advisable to review and adjust the patient's dose as required.

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, ibuprofen tablets are contraindicated for the treatment of peri-operative pain 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

Increased cardiovascular risks are associated with the use of this medication, including serious thrombotic events, myocardial infarction, and stroke, which may be fatal. Patients with pre-existing cardiovascular disease or risk factors are at heightened risk. It is recommended to use the lowest effective dose for the shortest duration necessary.

Hypertension may develop or worsen with NSAID use; therefore, blood pressure should be monitored closely. Additionally, fluid retention and edema have been reported, necessitating caution in patients with congestive heart failure or similar conditions.

Serious gastrointestinal adverse events, such as inflammation, bleeding, ulceration, and perforation, can occur at any time, with or without warning symptoms. Caution is advised for patients with a history of ulcer disease or gastrointestinal bleeding. Long-term use of NSAIDs may also lead to renal injury, particularly in patients with impaired renal function, heart failure, liver dysfunction, or those concurrently taking diuretics and ACE inhibitors.

Anaphylactoid reactions may occur in individuals without prior exposure, and emergency medical assistance should be sought immediately in such cases. Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis, can arise without warning. Discontinuation of the medication is advised at the first sign of a skin rash or any hypersensitivity reaction. Use during late pregnancy is contraindicated due to the risk of premature closure of the ductus arteriosus.

Ibuprofen is not a substitute for corticosteroids and does not treat corticosteroid insufficiency. If discontinuing corticosteroids, a gradual tapering is recommended. Liver function tests should be monitored, as significant elevations may occur; the medication should be discontinued if symptoms of liver disease develop. Long-term NSAID users should have their hemoglobin or hematocrit levels monitored for signs of anemia, and patients with coagulation disorders or those on anticoagulants should be observed for changes in platelet function.

Caution is warranted in patients with asthma, particularly those with aspirin-sensitive asthma. Patients should be monitored for blurred vision or changes in color vision, with discontinuation of the medication if these symptoms occur. The possibility of aseptic meningitis should be considered if relevant symptoms develop.

For patients on long-term NSAID treatment, monitoring for signs or symptoms of gastrointestinal bleeding is essential. 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 for any anaphylactoid reactions, and the medication should be stopped at the first appearance of a skin rash or any other sign of hypersensitivity. If symptoms consistent with liver disease arise, ibuprofen should also be discontinued.

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 and gastrointestinal risks. The use of NSAIDs is associated with an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may escalate with prolonged use, particularly in patients with existing cardiovascular disease or risk factors. Additionally, NSAIDs can lead to serious gastrointestinal adverse events, such as bleeding, ulceration, and perforation of the stomach or intestines, which may also be fatal. These events can occur at any time during treatment and may present without warning symptoms. Elderly patients are particularly susceptible to these serious gastrointestinal complications.

Common gastrointestinal adverse 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 accompanied by 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, and alopecia. Rare but serious reactions include 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 adverse reactions may involve 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 include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

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

Allergic reactions can present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Other allergic conditions may 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 adverse reactions reported include dry eyes and mouth, gingival ulcers, and rhinitis.

Drug Interactions

Concomitant use of certain medications with ibuprofen may lead to significant drug interactions, which can affect therapeutic outcomes and 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.

• Diuretics: Ibuprofen has been shown to diminish the natriuretic effect of diuretics such as furosemide and thiazides in some patients, likely due to the inhibition of renal prostaglandin synthesis. Close monitoring for signs of renal failure and assessment of diuretic efficacy is recommended during concomitant therapy.

• Warfarin-Type Anticoagulants: While short-term studies have not demonstrated a significant effect of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of NSAIDs and anticoagulants may lead to a higher risk of serious gastrointestinal bleeding. Caution is advised when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

• Aspirin: Co-administration of ibuprofen with aspirin may reduce the protein binding of aspirin, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction remains unclear, but the concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

• Lithium: Ibuprofen can elevate plasma lithium levels and decrease renal clearance of lithium, with observed increases in mean minimum lithium concentration and reductions in renal clearance during concurrent administration. Patients should be monitored closely for signs of lithium toxicity when these drugs are used together.

• Methotrexate: NSAIDs may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is warranted when administering NSAIDs alongside methotrexate.

H-2 Antagonists: Studies indicate that the co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine does not significantly affect ibuprofen serum concentrations, suggesting no clinically relevant interaction.

In summary, careful consideration and monitoring are advised when ibuprofen is used in conjunction with the aforementioned drug classes 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 ibuprofen in this population. Further studies are needed to determine appropriate dosing and outcomes in children and adolescents.

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 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 tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Particular caution is advised regarding the use of ibuprofen during late pregnancy due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, specifically the closure of the ductus arteriosus. Consequently, healthcare professionals should avoid prescribing ibuprofen to pregnant patients in the later stages of pregnancy unless absolutely necessary.

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 breastfeeding 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 use of NSAIDs in these patients may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate 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 administered NSAIDs. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in patients where renal prostaglandins play a compensatory role in maintaining renal perfusion. In individuals with compromised liver function, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate overt renal decompensation.

Patients with hepatic impairment, especially those with concurrent renal dysfunction, heart failure, or those taking diuretics and ACE inhibitors, are at an increased risk for these adverse reactions. Therefore, careful monitoring of renal function is recommended in this population. Should any signs of renal toxicity arise, discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state. It is advisable to assess liver function and renal parameters regularly to ensure patient safety and to adjust dosages as necessary based on individual patient response and tolerance.

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 patient 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 admission, the child received oxygen and parenteral fluids, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen. Two hours post-ingestion, the child's condition stabilized; however, she continued to respond solely to painful stimuli and experienced intermittent apnea lasting 5 to 10 seconds. The patient was subsequently admitted to intensive care, where sodium bicarbonate, along with dextrose and normal saline infusions, was administered. By four hours after 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 post-ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional 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 µg/mL 90 minutes after ingestion, which is about 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. 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 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

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 tablets 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, use during late pregnancy should be avoided.

In studies involving rats, the administration of NSAIDs has been associated with an increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown.

Postmarketing Experience

Postmarketing experience has identified several important considerations regarding the use of ibuprofen tablets. Anemia has been reported in patients receiving NSAIDs, including ibuprofen, potentially due to fluid retention, gastrointestinal blood loss, or effects on erythropoiesis. Patients undergoing long-term NSAID treatment should have their hemoglobin or hematocrit monitored if they exhibit signs or symptoms of anemia.

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

NSAIDs, including ibuprofen, are known to inhibit platelet aggregation and may prolong bleeding time in some patients. While their effect on platelet function is less pronounced and reversible compared to aspirin, patients with coagulation disorders or those receiving anticoagulants should be closely monitored for potential adverse effects.

Aseptic meningitis, accompanied by fever and coma, has been reported rarely in patients on ibuprofen therapy. This condition appears more likely in patients with systemic lupus erythematosus and related connective tissue diseases, but cases have also occurred in individuals without underlying chronic conditions. The possibility of ibuprofen being related to the development of meningitis should be considered if symptoms arise.

Reports indicate that NSAIDs may reduce the antihypertensive effect of ACE inhibitors, warranting caution in patients taking both medications concurrently. Although several short-term controlled studies have not demonstrated significant effects of ibuprofen on prothrombin times or other clotting factors in individuals on coumarin-type anticoagulants, bleeding events have been reported. Therefore, physicians should exercise caution when prescribing ibuprofen to patients on anticoagulants, as the combined use of warfarin and NSAIDs may increase the risk of serious gastrointestinal bleeding.

Patient Counseling

Patients should be informed of essential information before initiating therapy with ibuprofen tablets, as well as periodically during the course of ongoing therapy. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be made aware that ibuprofen, like other NSAIDs, may cause serious cardiovascular (CV) side effects, including myocardial infarction (MI) or stroke, which could lead to hospitalization or even death. Although serious CV events can occur without warning symptoms, patients should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to seek medical advice if they observe any of these indicative signs or symptoms, emphasizing the importance of follow-up regarding cardiovascular effects.

Additionally, patients should be informed that ibuprofen can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may also result in hospitalization or death. Serious GI tract ulcerations and bleeding can occur without warning symptoms; therefore, patients should be vigilant for signs such as epigastric pain, dyspepsia, melena, or hematemesis. They should be instructed to seek medical advice if they experience any of these symptoms, highlighting the importance of monitoring for gastrointestinal effects.

Patients should also be made aware that ibuprofen can lead to serious skin side effects, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Although serious skin reactions may occur without warning, patients should be alert for signs such as skin rash, blisters, fever, or other hypersensitivity symptoms like 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.

It is important for patients to promptly report any signs or symptoms of unexplained weight gain or edema to their physicians. They should also be informed about the warning signs and symptoms of hepatotoxicity, which 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 be educated on the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat. In such cases, they should be instructed to seek immediate emergency help.

Finally, patients should be advised 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 accordance with the National Drug Code (NDC) 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. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as serious ulcerations and bleeding can occur unexpectedly. For patients undergoing long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that complete blood counts (CBC) and chemistry profiles be assessed periodically to ensure safety.

In cases where patients exhibit clinical signs and symptoms indicative of liver or renal disease, or if systemic manifestations such as eosinophilia or rash develop, it is crucial to discontinue ibuprofen tablets. Additionally, if abnormal liver function tests persist or worsen, immediate cessation of the medication is advised.

FDA Insert (PDF)

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

View full prescribing information (PDF)