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 very slightly soluble in water, with a solubility of less than 1 mg/mL, but 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 available in dosages of 400 mg, 600 mg, and 800 mg for oral administration. The formulation includes several inactive ingredients: 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

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 with ibuprofen tablets, the dose and frequency 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, ibuprofen tablets should be administered 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 as 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 at the initiation of therapy or in response to treatment efficacy.

In general, patients with rheumatoid arthritis may require higher doses of ibuprofen tablets compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should be utilized, as a linear blood level dose-response relationship exists with single doses up to 800 mg.

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

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of ibuprofen is not recommended in individuals who have a history of asthma, urticaria, or allergic-type reactions following the administration of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Furthermore, ibuprofen tablets are contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Clinical trials have demonstrated an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). This risk may be particularly pronounced in patients with existing CV disease or risk factors. It is recommended that the lowest effective dose of NSAIDs be utilized for the shortest duration necessary. Healthcare professionals should educate patients on recognizing the signs and symptoms of serious CV events and advise them on the appropriate actions to take should these occur. Notably, there is no consistent evidence that the concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events linked to NSAID use; in fact, combining aspirin with an NSAID may elevate the risk of serious gastrointestinal (GI) events. Additionally, two large clinical trials have indicated an increased incidence of myocardial infarction and stroke in patients treated with a COX-2 selective NSAID following coronary artery bypass graft (CABG) surgery.

NSAIDs have the potential to induce new hypertension or exacerbate preexisting hypertension. Therefore, it is imperative that blood pressure be monitored closely throughout the duration of NSAID treatment.

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 congestive heart failure.

Serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation, can occur with NSAID use and may be fatal. These events can arise at any time, with or without warning symptoms. Patients with a prior history of ulcer disease or GI bleeding are at more than a tenfold increased risk for developing a GI bleed. Both patients and healthcare providers should remain vigilant for signs and symptoms of GI ulcerations and bleeding during NSAID therapy, and prompt evaluation and treatment should be initiated if a serious GI event is suspected.

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 taking diuretics and ACE inhibitors, and the elderly. Typically, discontinuation of NSAID therapy leads to recovery of renal function. In patients with advanced renal disease, the use of ibuprofen tablets is not recommended; if therapy is deemed necessary, close monitoring of renal function is essential.

Anaphylactoid reactions may occur in patients who have not previously been exposed to NSAIDs. In such cases, emergency medical assistance should be sought immediately.

Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can occur without prior warning. Patients should be instructed to discontinue the medication at the first sign of a skin rash or any indication of hypersensitivity and to contact their healthcare provider.

In late pregnancy, the use of ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus.

Healthcare professionals should ensure that patients are aware of the need to seek emergency medical help in the event of an anaphylactoid reaction and to discontinue the medication and consult their physician at the first appearance of a skin rash or any other sign of hypersensitivity.

Side Effects

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

Serious adverse reactions include cardiovascular events such as myocardial infarction, stroke, and other thrombotic events, which can be fatal. The risk of these events may increase with the duration of use, particularly in patients with existing cardiovascular disease or risk factors. Gastrointestinal complications, including bleeding, ulceration, and perforation of the stomach or intestines, are also serious and can occur without warning. Elderly patients are at a heightened risk for these gastrointestinal events. Additionally, renal effects such as acute renal failure and renal papillary necrosis have been reported, particularly with long-term use.

Common gastrointestinal adverse reactions reported include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal symptoms may include vomiting, indigestion, constipation, and bloating. In rare cases, patients have experienced gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, and pancreatitis.

Central nervous system effects may manifest as dizziness, headache, and nervousness. More severe reactions can include depression, insomnia, confusion, emotional liability, and somnolence. Rarely, aseptic meningitis with fever and coma has been observed. Patients may also report paresthesias, hallucinations, and dream abnormalities.

Dermatologic reactions can range from mild rashes and pruritus to more severe conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and photoallergic skin reactions. Alopecia and neuritis have also been noted.

In the realm of special senses, tinnitus and hearing loss have been reported, along with amblyopia, conjunctivitis, diplopia, and optic neuritis.

Hematologic adverse reactions include neutropenia, agranulocytosis, aplastic anemia, and hemolytic anemia, with some cases being Coombs positive. Thrombocytopenia and eosinophilia have also been observed, along with bleeding episodes such as epistaxis and menorrhagia.

Metabolic and endocrine effects may include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

Cardiovascular reactions can involve edema and fluid retention, which generally respond promptly to discontinuation of the drug. Congestive heart failure may occur in patients with marginal cardiac function, alongside elevated blood pressure and palpitations. Arrhythmias, including sinus tachycardia and bradycardia, have also been reported.

Allergic reactions can present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, with severe cases leading to anaphylaxis and bronchospasm. Other allergic manifestations include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal adverse reactions may include decreased creatinine clearance, polyuria, azotemia, cystitis, and hematuria.

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

Patients should be monitored for these adverse reactions, and any severe or concerning symptoms should prompt immediate medical evaluation.

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 already receiving ACE-inhibitors.

• Diuretics: Ibuprofen may diminish the natriuretic effect of diuretics such as furosemide and thiazides, potentially due to the inhibition of renal prostaglandin synthesis. Patients on concomitant therapy should be monitored closely for signs of renal impairment and to ensure the efficacy of diuretics.

• Warfarin-type Anticoagulants: While short-term studies have not shown a significant effect of ibuprofen on prothrombin times in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of NSAIDs and anticoagulants can 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 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 shown to elevate plasma lithium levels and decrease 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 for signs of lithium toxicity.

• 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 recommended 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, healthcare professionals should exercise caution 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, 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. 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. In patients with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs in these individuals 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 the highest risk for these adverse effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. In cases where NSAID therapy is necessary, close monitoring of renal function is advisable. 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 for these patients.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this drug. 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 1.5 hours following the ingestion of 7 to 10 ibuprofen tablets (400 mg), a 19-month-old child weighing 12 kg 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 stabilized, although she continued to respond solely to painful stimuli and experienced intermittent apnea lasting 5 to 10 seconds. The child was subsequently admitted to intensive care, where sodium bicarbonate, along with 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 8.5 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 reported dizziness, with nystagmus observed during examination. Following hospitalization, the patient received parenteral hydration and was placed on bed rest for three days, 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 should be noted 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. Ibuprofen tablets are classified as Pregnancy Category C, indicating that 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, particularly the closure of the ductus arteriosus, use during late pregnancy should be avoided. In studies involving rats, the administration of NSAIDs, similar to other drugs that inhibit prostaglandin synthesis, resulted in 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 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. The effect of NSAIDs on platelet function is quantitatively less, of shorter duration, and reversible compared to aspirin. Patients receiving ibuprofen who may be adversely affected by changes 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 ibuprofen tablets and periodically throughout the course of treatment. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be made aware that ibuprofen tablets, like other NSAIDs, may lead to serious cardiovascular (CV) side effects, including myocardial infarction (MI) or stroke, which could result in hospitalization or even death. Although serious CV events can occur without warning symptoms, patients should be vigilant for signs 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 health.

Additionally, patients should be informed that ibuprofen tablets can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may also lead to hospitalization or death. Serious GI tract ulcerations and bleeding can occur without warning symptoms; therefore, patients should be alert 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 of the potential for serious skin side effects associated with ibuprofen tablets, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Although serious skin reactions can occur without warning, patients should be vigilant for signs such as skin rash, blisters, fever, or other hypersensitivity symptoms like itching. They should be advised to discontinue the medication immediately and contact their physician if any type of rash develops.

It is important for patients to promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider. Furthermore, patients 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 symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should also 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 during late pregnancy, as with other NSAIDs, 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 ranging from 20° to 25°C (68° to 77°F). Care should be taken to ensure that the storage environment maintains these temperature conditions to preserve the integrity of the product.

Additional Clinical Information

Physicians should monitor patients on long-term NSAID treatment for signs or symptoms of gastrointestinal (GI) bleeding. It is recommended that these patients have their complete blood count (CBC) and chemistry profile checked periodically. If any clinical signs or symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, Ibuprofen Tablets, USP should be discontinued.

Patients should be counseled on the serious cardiovascular risks associated with ibuprofen, including myocardial infarction and stroke, and the importance of recognizing related symptoms. They should also be made aware of potential gastrointestinal discomfort and serious GI side effects, such as ulcers and bleeding, and instructed to recognize these signs. Additionally, patients must be informed about the risk of serious skin reactions, hepatotoxicity, and anaphylactoid reactions, advising them to seek immediate medical attention if these occur. Patients should report any unexplained weight gain or edema to their healthcare provider. Furthermore, 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)