Ibuprofen

Description

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

IBUPROFEN 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, magnesium stearate, microcrystalline cellulose, OPADRY® II, pregelatinized starch, sodium starch glycollate, and talc.

Uses and Indications

IBUPROFEN tablets are indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Additionally, IBUPROFEN 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 this medication in pediatric populations is not recommended until further data is available.

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, the dose and frequency of IBUPROFEN tablets should be adjusted to meet the specific needs of each patient.

The total daily dose should not exceed 3200 mg. In cases where gastrointestinal complaints arise, it is advisable to administer IBUPROFEN tablets 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 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). The dosage should be tailored to each patient, with adjustments made based on the severity of symptoms. 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 utilized.

In chronic conditions, a therapeutic response to IBUPROFEN tablets may be observed within a few days to a week, but is most commonly seen by two weeks. Once a satisfactory response is achieved, the patient's dosage should be reviewed and adjusted as necessary.

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

In the treatment of dysmenorrhea, IBUPROFEN tablets should be initiated at the earliest onset of pain, with a recommended 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 tablets is not recommended for 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. Furthermore, IBUPROFEN tablets are contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

NSAIDs, including IBUPROFEN, are associated with an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may escalate with prolonged use, particularly in patients with existing cardiovascular disease or those possessing risk factors for cardiovascular conditions. Therefore, careful consideration is warranted when prescribing these medications to such populations.

IBUPROFEN tablets are contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery. This contraindication is critical to ensure patient safety and prevent potential complications.

The use of NSAIDs is also linked to a heightened risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These gastrointestinal events may occur unexpectedly at any point during treatment, often without prior warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal complications, necessitating vigilant monitoring.

To ensure safe use of IBUPROFEN, healthcare professionals should monitor patients for signs or symptoms indicative of gastrointestinal bleeding. For patients undergoing long-term NSAID therapy, it is recommended that a complete blood count (CBC) and chemistry profile be assessed periodically to detect any potential adverse effects. Should any clinical signs or symptoms suggestive of liver or renal disease arise, or if systemic manifestations such as eosinophilia or rash develop, or if abnormal liver tests persist or worsen, it is imperative to discontinue the use of IBUPROFEN tablets promptly.

Side Effects

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

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 adverse reactions, occurring in more than 1% but less than 3% of patients, include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Central nervous system effects may manifest as dizziness, headache, and nervousness. Dermatologic reactions can include rash (including maculopapular types) and pruritus. Other common reactions involve special senses, such as tinnitus, and metabolic/endocrine issues like decreased appetite. Cardiovascular reactions may present as edema and fluid retention, which typically resolve upon discontinuation of the drug. Allergic reactions have been noted, including a syndrome characterized by abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Renal adverse reactions may include acute renal failure, decreased creatinine clearance, and hematuria, among others. Miscellaneous reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

Adverse reactions with a precise incidence unknown but a probable causal relationship (less than 1%) include gastrointestinal issues such as gastric or duodenal ulcers with bleeding, gastrointestinal hemorrhage, and pancreatitis. Central nervous system effects may include depression, insomnia, confusion, and aseptic meningitis. Dermatologic reactions can involve vesiculobullous eruptions and Stevens-Johnson syndrome. Hematologic reactions may include neutropenia and thrombocytopenia. Cardiovascular issues such as congestive heart failure in patients with marginal cardiac function and elevated blood pressure have also been reported.

There are additional adverse reactions with a precise incidence unknown and a causal relationship that remains unclear. These include central nervous system effects like paresthesias and hallucinations, dermatologic reactions such as toxic epidermal necrolysis, and special senses issues like diplopia and cataracts. Hematologic concerns may involve bleeding episodes, while metabolic/endocrine reactions can include gynecomastia and hypoglycemic reactions. Cardiovascular arrhythmias and renal complications such as renal papillary necrosis have also been noted.

Healthcare providers should monitor patients for these adverse reactions and weigh the benefits against the risks when prescribing this medication.

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 ibuprofen 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 ibuprofen, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction is unclear, but the concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

• Lithium: Ibuprofen has been associated with elevated plasma lithium levels and decreased renal clearance of lithium. In a study, the mean minimum lithium concentration increased by 15%, and renal clearance decreased by 19% during concurrent administration. Patients receiving both ibuprofen and lithium should be monitored closely for signs of lithium toxicity.

• Methotrexate: NSAIDs, including ibuprofen, 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 that no dosage adjustments are necessary in this context.

In summary, careful consideration and monitoring are advised when ibuprofen is used in conjunction with 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, which may necessitate careful monitoring and potential dose adjustments. Geriatric patients may have altered pharmacokinetics and pharmacodynamics, which can affect drug efficacy and safety. Therefore, close observation for any signs of intolerance or complications is recommended when initiating or adjusting therapy in elderly individuals.

Pregnancy

Pregnant patients should be aware that IBUPROFEN tablets are classified as Pregnancy Category C. While teratogenic effects have been noted, animal studies conducted in rats and rabbits did not demonstrate developmental abnormalities. However, the response in humans remains unpredictable. There are no adequate and well-controlled studies in pregnant women; therefore, IBUPROFEN tablets should only be used during pregnancy if the potential benefits justify the potential risks to the fetus.

Particular caution is advised when considering the use of IBUPROFEN during late pregnancy, as nonsteroidal anti-inflammatory drugs (NSAIDs) are known to affect the fetal cardiovascular system, specifically concerning the closure of the ductus arteriosus. The effects of IBUPROFEN on labor and delivery in pregnant women are not well understood. Animal studies involving NSAIDs have indicated an increased incidence of dystocia, delayed parturition, and decreased pup survival. Healthcare professionals should weigh these risks carefully 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 breastfeeding or discontinue the drug.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the drug insert text regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as there is no available data to guide treatment decisions in this population. Regular monitoring of renal function may be advisable in these patients, although specific recommendations are not provided.

Hepatic Impairment

There is no information available regarding the use of this medication in patients with hepatic impairment. Consequently, there are no dosage adjustments, special monitoring requirements, or precautions specified for individuals with compromised liver function. Healthcare professionals should exercise clinical judgment when considering the use of this medication in patients with liver problems, as the absence of data does not preclude the need for careful evaluation and monitoring based on individual patient circumstances.

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 level of stimulation 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 appeared stable; 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 could be easily aroused, sit independently, and respond to verbal commands. A blood level of ibuprofen measured 102.9 μg/mL approximately 8½ hours post-ingestion, and by 12 hours, the child had 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 reported dizziness, with nystagmus noted during examination. Following hospitalization, the patient received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

In instances of acute ibuprofen 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

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 in 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, use during late pregnancy should be avoided. In rat studies involving NSAIDs, as with other drugs that inhibit prostaglandin synthesis, there was 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

In two postmarketing clinical studies, a higher 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 taking 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients receiving 2400 mg of ibuprofen daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were noted in these studies.

Anemia has been reported in patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets. This condition may arise from factors such as fluid retention, occult or gross gastrointestinal blood loss, or an incompletely characterized effect on erythropoiesis.

NSAIDs are known to inhibit platelet aggregation and may prolong bleeding time in some patients. However, their effect on platelet function is quantitatively less, of shorter duration, and reversible compared to aspirin. Patients receiving ibuprofen tablets who may be at risk due to alterations in platelet function, such as those with coagulation disorders or those on anticoagulant therapy, should be monitored closely.

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as IBUPROFEN, and periodically during the course of ongoing therapy. They should be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients that IBUPROFEN tablets, like other NSAIDs, may cause serious cardiovascular (CV) side effects, including myocardial infarction (MI) or stroke, which may result in hospitalization and even death. Patients should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, and slurring of speech. They should be instructed to seek medical advice if they observe any of these indicative signs or symptoms and be apprised of the importance of follow-up.

Patients should also be made aware that IBUPROFEN tablets can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects, such as ulcers and bleeding, which may lead to hospitalization and even 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, and hematemesis. They should be encouraged to seek medical advice if they experience any of these symptoms and understand the importance of follow-up.

Additionally, healthcare providers should inform patients that IBUPROFEN tablets can lead to serious skin side effects, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization and even death. Patients should be alert for signs such as skin rash, blisters, fever, or other hypersensitivity reactions like itching. They should be instructed to stop the medication immediately if any type of rash develops and to contact their physician as soon as possible.

Patients should 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, including nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms. If these occur, patients should be instructed to discontinue therapy and seek immediate medical attention.

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

Finally, healthcare providers should inform patients that in late pregnancy, as with other NSAIDs, IBUPROFEN tablets should be avoided due to the risk of 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 should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), in accordance with USP guidelines. Proper storage conditions are essential to maintain the integrity of the product.

Additional Clinical Information

Clinicians are advised to monitor 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 checked periodically. Additionally, if patients exhibit clinical signs and symptoms indicative of liver or renal disease, or if systemic manifestations such as eosinophilia or rash develop, or if abnormal liver tests persist or worsen, the use of ibuprofen tablets should be discontinued.

FDA Insert (PDF)

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

View full prescribing information (PDF)