Ibuprofen

Description

Ibuprofen Tablets, USP contain the active ingredient ibuprofen, which is chemically defined as (±) – 2 – (p – isobutylphenyl) propionic acid. Ibuprofen appears as a white 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 is represented below.

Ibuprofen Tablets, USP 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, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, talc, stearic acid, and titanium dioxide.

Uses and Indications

Ibuprofen Tablets, USP are indicated for the relief of the signs and symptoms associated with rheumatoid arthritis and osteoarthritis. This medication is also 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, USP in pediatric populations have not been conducted. Therefore, the use of this medication in children is not recommended until further data is available.

Dosage and Administration

For the management of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage is between 1200 mg and 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 times a day (tid) or four times a day (qid). It is important not to exceed a total daily dose of 3200 mg.

For the relief of mild to moderate pain, a dosage of 400 mg may be taken every 4 to 6 hours as needed. In cases of dysmenorrhea, the recommended dosage is 400 mg every 4 hours as necessary for pain relief.

To minimize gastrointestinal complaints, it is advised to administer Ibuprofen Tablets, USP with meals or milk.

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). Furthermore, ibuprofen tablets are contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Patients receiving NSAID therapy should be closely monitored for several critical safety concerns.

Cardiovascular Effects Clinical trials indicate an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, which may be fatal. All NSAIDs carry a similar risk, particularly in patients with known CV disease or risk factors. It is recommended that the lowest effective dose be utilized for the shortest duration necessary. Patients should be educated on recognizing the signs and symptoms of serious CV events and the appropriate actions to take if they occur. Notably, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use.

Hypertension NSAIDs have the potential to induce new hypertension or exacerbate existing hypertension. Blood pressure should be monitored closely during the initiation of NSAID treatment and throughout the duration of therapy.

Congestive Heart Failure and Edema Fluid retention and edema have been reported in some patients taking NSAIDs. Caution is advised when prescribing these medications to patients with a history of fluid retention or heart failure.

Gastrointestinal Effects NSAIDs can lead to serious gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. Patients should be vigilant for signs and symptoms of GI ulcerations and bleeding during NSAID therapy. If a serious GI event is suspected, immediate evaluation and treatment are warranted, and NSAID therapy should be discontinued until such events are ruled out.

Renal Effects Long-term use of NSAIDs has been associated with renal injury. Patients at heightened risk include those with impaired renal function, heart failure, liver dysfunction, those on diuretics and ACE inhibitors, and the elderly. Typically, discontinuation of NSAID therapy leads to recovery of renal function.

Advanced Renal Disease The use of ibuprofen tablets is not recommended in patients with advanced renal disease. If treatment is deemed necessary, close monitoring of renal function is essential.

Anaphylactoid Reactions Anaphylactoid reactions may occur in patients without prior exposure to the medication. In the event of such a reaction, emergency medical assistance should be sought immediately.

Skin Reactions Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), may occur. The drug should be discontinued at the first sign of a skin rash or any other indication of hypersensitivity.

Patients are advised to discontinue NSAID use and contact their healthcare provider at the first appearance of a skin rash or any other sign of hypersensitivity. Emergency medical help should be sought in cases of anaphylactoid reactions.

Side Effects

Patients may experience a range of adverse reactions while using this medication, which can be categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular events such as myocardial infarction, stroke, and serious cardiovascular thrombotic events, which can be fatal. The risk of these events may increase with the duration of use, particularly in patients with preexisting cardiovascular disease or risk factors. Additionally, serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, have been reported. These events can occur without warning and may also be fatal, with elderly patients being at greater risk. Renal effects, such as acute renal failure and renal papillary necrosis, have been observed, particularly with long-term administration.

Common gastrointestinal adverse reactions include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal issues may involve constipation, bloating, and flatulence. More severe gastrointestinal complications, such as gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis, have also been reported.

Central nervous system reactions may include dizziness, headache, and nervousness, with more serious effects such as depression, insomnia, confusion, and somnolence noted in some patients. Rarely, aseptic meningitis with fever and coma has been observed. Dermatologic reactions can range from mild rashes and pruritus to severe conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

Hematologic adverse reactions include neutropenia, agranulocytosis, and thrombocytopenia, with some patients experiencing bleeding episodes. Metabolic and endocrine effects may manifest as decreased appetite, gynecomastia, and hypoglycemic reactions.

Patients may also experience cardiovascular issues such as edema and fluid retention, which generally respond promptly to discontinuation of the drug. Other cardiovascular concerns include elevated blood pressure and arrhythmias.

Allergic reactions can present as anaphylaxis, bronchospasm, and serum sickness, among others. Renal adverse reactions may include decreased creatinine clearance and hematuria.

Miscellaneous reactions reported include dry eyes and mouth, gingival ulcers, and rhinitis.

It is important for patients to be aware of these potential adverse reactions and to consult healthcare professionals if they experience any concerning symptoms.

Drug Interactions

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

Antihypertensives

• 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 already receiving ACE-inhibitors.

Antiplatelet Agents

• Aspirin: The co-administration of ibuprofen with aspirin may reduce the protein binding of aspirin; however, the clearance of free ibuprofen remains unchanged. Due to the potential for increased adverse effects, the concomitant use of ibuprofen and aspirin is generally not recommended.

Diuretics

• Furosemide and Thiazides: Ibuprofen may diminish the natriuretic effect of diuretics such as furosemide and thiazides in some patients, likely due to the inhibition of renal prostaglandin synthesis. Patients should be closely monitored for signs of renal failure and to ensure the efficacy of diuretics during concurrent NSAID therapy.

Lithium

• Ibuprofen has been shown to elevate plasma lithium levels while decreasing renal clearance of lithium. Specifically, the mean minimum lithium concentration can increase by 15%, and renal clearance may decrease by 19% with concomitant use. Patients should be monitored for signs of lithium toxicity.

Methotrexate

• NSAIDs may competitively inhibit the accumulation of methotrexate, potentially increasing its toxicity. Caution is advised when administering NSAIDs alongside methotrexate.

Anticoagulants

• Warfarin-type anticoagulants: While studies have not consistently demonstrated a significant effect of ibuprofen on prothrombin times or other clotting factors in patients on coumarin-type anticoagulants, there is a reported risk of bleeding. The risk of serious gastrointestinal bleeding is heightened when ibuprofen is used in conjunction with anticoagulants.

H-2 Antagonists

• The co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine does not appear to significantly affect ibuprofen serum concentrations.

Healthcare providers should exercise caution and consider appropriate monitoring or dosage adjustments when prescribing ibuprofen in conjunction with these medications to mitigate potential adverse effects.

Packaging & NDC

The table below lists all NDC Code configurations of Ibuprofen, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

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.

Geriatric Use

Caution should be exercised when treating elderly patients, specifically those aged 65 years and older. Due to the potential for altered pharmacokinetics and increased sensitivity to medications in this population, careful consideration of dosage adjustments and monitoring is essential. Healthcare providers are advised to assess the individual health status and comorbidities of geriatric patients to ensure safe and effective treatment.

Pregnancy

Pregnancy Category C. Reproductive studies conducted in rats and rabbits have not demonstrated 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. 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 known to 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 are unknown.

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. Renal toxicity may occur in patients where renal prostaglandins play a compensatory role in maintaining renal perfusion. The administration of an NSAID can lead to a dose-dependent reduction in prostaglandin formation, which may subsequently decrease renal blood flow and precipitate overt renal decompensation.

Patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly are at the greatest risk for these adverse reactions. In cases where NSAID therapy is discontinued, recovery to the pretreatment state is typically observed.

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 tablets therapy is deemed necessary, close monitoring of the patient's renal function is advised.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the prescribing information.

Overdosage

Approximately 1 ½ hours after 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 admission, the child received oxygen and parenteral fluids, and a greenish-yellow fluid was aspirated from the stomach, with no evidence of ibuprofen detected. Two hours post-ingestion, the child's condition stabilized; however, she continued to respond only to painful stimuli and experienced periods of 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 μg/mL approximately 8 ½ hours post-ingestion, and by 12 hours, the child appeared to have fully recovered.

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 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 was observed. 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 should be noted that little drug may be recovered 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 employed, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

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 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, the use of ibuprofen during late pregnancy should be avoided.

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

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.

Aseptic meningitis, accompanied by fever and coma, has been reported 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 cases have also been documented in individuals without underlying chronic diseases. If a patient on ibuprofen tablets exhibits signs or symptoms of meningitis, the potential association with ibuprofen therapy should be evaluated.

Patient Counseling

Patients should be informed of essential information before initiating therapy with ibuprofen tablets 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 discuss the potential for serious cardiovascular (CV) side effects associated with ibuprofen, including myocardial infarction (MI) and stroke, which may lead to hospitalization or death. Patients should be made aware that serious CV events can occur without warning symptoms. They should be instructed to remain vigilant for signs and symptoms such as chest pain, shortness of breath, weakness, or slurring of speech, and to seek medical advice if they observe any of these indicative signs.

It is also important to inform patients that ibuprofen can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects, including ulcers and bleeding, which may result in hospitalization or death. Patients should be advised to be alert for signs and symptoms of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis. They should be encouraged to seek medical advice if they experience any of these symptoms.

Healthcare providers should make patients aware of the risk of serious skin side effects associated with ibuprofen, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may also lead to hospitalization or death. Patients should be instructed to monitor for signs and symptoms such as skin rash, blisters, fever, or other hypersensitivity reactions like itching. They should be advised to discontinue the medication immediately and contact their physician if any rash develops.

Patients should be encouraged to promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider. Additionally, they should be informed about the warning signs of hepatotoxicity, including nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms. If these occur, patients should be instructed to stop therapy and seek immediate medical attention.

Healthcare providers should also educate patients on the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. Patients should be advised to seek immediate emergency help if they experience these symptoms.

Finally, it is crucial to inform patients that ibuprofen should be avoided in late pregnancy, as it may cause 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

Physicians are advised to monitor patients for signs or symptoms of gastrointestinal (GI) bleeding, particularly in those undergoing long-term treatment with NSAIDs. Regular checks of complete blood count (CBC) and chemistry profiles are recommended. If patients exhibit clinical signs consistent with liver or renal disease, or if abnormal liver tests persist or worsen, discontinuation of Ibuprofen Tablets, USP is warranted.

Patients should be counseled on several serious potential side effects associated with ibuprofen use. They should be vigilant for cardiovascular events, including myocardial infarction (MI) or stroke, as well as GI complications such as ulcers and bleeding. Symptoms indicating these issues include chest pain, shortness of breath, epigastric pain, and melena. Additionally, patients should be aware of serious skin reactions, signs of hepatotoxicity, unexplained weight gain, and anaphylactoid reactions, all of which require prompt medical attention. It is also important to inform patients that ibuprofen should be avoided in late pregnancy due to the risk of premature closure of the ductus arteriosus.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Ibuprofen as submitted by H. J. Harkins Company, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)