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 its very slight solubility in water (less than 1 mg/mL) and its ready solubility in organic solvents such as ethanol and acetone. This formulation is classified as a nonsteroidal anti-inflammatory drug (NSAID) and is available in oral dosage forms of 400 mg, 600 mg, and 800 mg tablets. The inactive ingredients include 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. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Controlled clinical trials to establish the safety and effectiveness of Ibuprofen Tablets, USP in pediatric populations have not been conducted. Therefore, caution is advised when considering the use of this medication in children.

Dosage and Administration

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

Ibuprofen Tablets, USP should be administered with meals or milk if gastrointestinal complaints occur.

After the initial therapy, healthcare professionals should observe the patient's response and adjust the dose and frequency accordingly to meet individual patient needs. The dosage may be tailored based on the severity of symptoms, with potential adjustments to either lower or raise the dose as required. A therapeutic response is typically observed within a few days to a week, but most often by two weeks. Once a satisfactory response is achieved, it is advisable to review and adjust the patient's dose as necessary.

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 other 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 fatal and is particularly pronounced in patients with existing CV disease or risk factors. It is imperative to use the lowest effective dose 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.

NSAIDs have the potential to induce new hypertension or exacerbate preexisting hypertension. Therefore, it is essential to monitor blood pressure closely during NSAID treatment to ensure patient safety.

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

The gastrointestinal (GI) effects of NSAIDs warrant significant attention, as they can lead to serious adverse events such as inflammation, bleeding, ulceration, and perforation, which may be fatal. These events can occur unexpectedly, with or without warning symptoms. Patients with a prior history of ulcer disease or gastrointestinal 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, particularly in patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy typically 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 without prior exposure to NSAIDs. In such cases, emergency medical assistance should be sought immediately. Additionally, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can occur. Patients should be instructed to discontinue use at the first sign of a skin rash or any other indication of hypersensitivity.

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

In summary, healthcare professionals must remain vigilant regarding these warnings and precautions to ensure the safe use of NSAIDs in their patients.

Side Effects

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

Gastrointestinal adverse reactions are among the most common and may include nausea, epigastric pain, heartburn, diarrhea, abdominal distress, vomiting, indigestion, constipation, and abdominal cramps or pain. More serious gastrointestinal events, such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, and abnormal liver function tests, have also been reported. Additionally, pancreatitis has been noted in some patients. It is important to recognize that serious gastrointestinal adverse events can occur at any time during treatment and without warning symptoms, particularly in elderly patients who are at greater risk.

Central nervous system reactions may include dizziness, headache, and nervousness, with more serious effects such as depression, insomnia, confusion, emotional liability, somnolence, and rare occurrences of aseptic meningitis with fever and coma. Other reported symptoms include paresthesias, hallucinations, and dream abnormalities.

Dermatologic reactions can range from common rashes and pruritus to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Alopecia and photoallergic skin reactions have also been observed.

Adverse reactions affecting the special senses include tinnitus, hearing loss, amblyopia, conjunctivitis, diplopia, and optic neuritis. Patients may also experience changes in vision, including scotomata and alterations in color vision.

Hematologic adverse reactions may manifest as neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), and thrombocytopenia, with or without purpura. Eosinophilia and decreases in hemoglobin and hematocrit have also been reported, along with bleeding episodes such as epistaxis and menorrhagia.

Metabolic and endocrine reactions include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis. Cardiovascular effects may involve edema, fluid retention, congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias such as 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 manifestations include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

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

Patients should be aware of the boxed warnings associated with this medication, which highlight the increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, particularly with prolonged use. Additionally, there is a significant risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation, which can be fatal. Patients with preexisting cardiovascular disease or risk factors may be at greater risk for these serious events.

Warnings also indicate that NSAIDs can lead to new or worsening hypertension, fluid retention, and edema, as well as renal injury, including renal papillary necrosis. Anaphylactoid reactions may occur in patients without prior exposure to the medication, and serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.

Finally, it is important to note that aseptic meningitis with fever and coma has been observed on rare occasions in patients undergoing ibuprofen therapy.

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

• Warfarin-type Anticoagulants: While short-term studies have not shown 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 it is generally not recommended to use ibuprofen and aspirin together 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 should be monitored closely for signs of lithium toxicity when these drugs are used together.

• 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 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.

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. 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 therapy with ibuprofen tablets 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 drug. Consequently, there are no established 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 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 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, 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 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 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 should be noted that minimal drug recovery is likely 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

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, particularly the closure of the ductus arteriosus, use during late pregnancy should be avoided.

In studies conducted with rats, the administration of NSAIDs, including ibuprofen, 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.

No specific details regarding animal pharmacology and toxicology beyond the effects noted in the nonclinical toxicology section are available.

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.

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.

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 follow-up.

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 may 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 if any 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 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 premature closure of the ductus arteriosus.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. 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 should monitor patients on long-term NSAID treatment for signs or symptoms of gastrointestinal (GI) bleeding and periodically check complete blood count (CBC) and chemistry profiles. If patients exhibit clinical signs consistent with liver or renal disease, systemic manifestations such as eosinophilia or rash, or if abnormal liver tests persist or worsen, Ibuprofen Tablets, USP should be discontinued.

Before initiating therapy with an NSAID, patients should be counseled on potential serious cardiovascular side effects, including myocardial infarction (MI) and stroke, and advised to recognize symptoms such as chest pain and shortness of breath. They should also be aware of possible GI discomfort and serious side effects like ulcers and bleeding, with instructions to report symptoms such as epigastric pain or melena. Additionally, patients should be informed about serious skin reactions, signs of hepatotoxicity, and anaphylactoid reactions, and should be advised to report unexplained weight gain or edema. It is important to note 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 RedPharm Drug Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)