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 tablets also contain several inactive ingredients, including 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, healthcare professionals should exercise caution when considering the use of this medication in children.

Dosage and Administration

For the treatment of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the suggested dosage ranges from 1200 mg to 3200 mg daily. Dosing may 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). Individual patient responses may vary, and some patients may benefit from a higher dosage of 3200 mg daily compared to 2400 mg. It is essential to tailor the dose to each patient and adjust it based on the severity of symptoms.

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

In cases of dysmenorrhea, a dosage of 400 mg may be administered every 4 hours as necessary for pain relief.

General administration instructions include a maximum total daily dose of 3200 mg. In the event of gastrointestinal complaints, it is recommended to administer Ibuprofen Tablets with meals or milk. The smallest effective dose should be utilized for the shortest duration that aligns with the individual treatment goals of the patient.

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

Patients receiving NSAID therapy should be closely monitored for several significant risks associated with their use.

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 profile, particularly in patients with known CV disease or risk factors. It is recommended to use the lowest effective dose for the shortest duration possible. 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. Furthermore, the combination of aspirin and an NSAID may elevate the risk of serious gastrointestinal (GI) events. Two large clinical trials have also demonstrated an increased incidence of myocardial infarction and stroke in patients treated with a COX-2 selective NSAID following coronary artery bypass graft (CABG) surgery.

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

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 fluid retention or heart failure.

Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation NSAIDs can lead to serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation, which can be fatal. Such events may occur at any time, with or without warning symptoms. Patients with a history of ulcer disease or GI bleeding are at more than a tenfold increased risk for developing a GI bleed. It is advisable to use the lowest effective dose for the shortest duration possible, and both patients and healthcare providers should remain vigilant for signs and symptoms of GI ulcerations and bleeding.

Renal Effects Long-term use of NSAIDs may result in 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.

Advanced Renal Disease The use of ibuprofen 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 can occur in patients without prior exposure to ibuprofen. It is contraindicated in individuals with the aspirin triad. Emergency medical assistance should be sought immediately in the event of an anaphylactoid reaction.

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

Pregnancy Ibuprofen should be avoided during late pregnancy due to the risk of premature closure of the ductus arteriosus.

In cases of anaphylactoid reactions, emergency medical help should be sought immediately. Patients are advised to discontinue use and contact their healthcare provider 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 serious 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 adverse reactions reported in clinical trials and postmarketing experiences include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, and constipation. Central nervous system effects may manifest as dizziness, headache, and nervousness, with more severe reactions including depression, insomnia, and confusion. Dermatologic reactions such as rash, pruritus, and more severe skin conditions like Stevens-Johnson syndrome and toxic epidermal necrolysis have also been observed.

Patients may experience hematologic reactions, including neutropenia, agranulocytosis, and thrombocytopenia, as well as metabolic/endocrine effects such as decreased appetite and gynecomastia. Cardiovascular reactions may include edema and fluid retention, which typically respond to discontinuation of the drug. Allergic reactions can range from mild symptoms to anaphylaxis, and renal issues may present as decreased creatinine clearance and hematuria.

Miscellaneous reactions such as dry eyes and mouth, gingival ulcer, and rhinitis have also been reported. Aseptic meningitis with fever and coma has been noted in rare cases among patients undergoing ibuprofen therapy.

Patients should be monitored for these adverse reactions, and any serious symptoms should prompt immediate medical attention.

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, likely 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 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 for signs of lithium toxicity when these drugs are used together.

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

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

In summary, careful consideration and monitoring are 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

The safety and effectiveness of ibuprofen tablets in pediatric patients have not been established. Therefore, caution should be exercised when considering the use of ibuprofen in this population. Further studies are needed to determine appropriate dosing and outcomes in children and adolescents.

Geriatric Use

Caution should be exercised when treating elderly patients (65 years and older) with this medication, as with any nonsteroidal anti-inflammatory drugs (NSAIDs). It is important for healthcare providers to consider the increased risk of adverse effects in this population. Monitoring for potential side effects and adjusting dosages as necessary may be warranted to ensure the safety and efficacy of treatment in geriatric patients.

Pregnancy

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 administration 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 advised. 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 medication. 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

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the time elapsed since ingestion.

Clinical Presentation A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg each). Approximately 1.5 hours post-ingestion, the child presented to the emergency department in a state of apnea and cyanosis, responding only to painful stimuli. Despite the severity of the symptoms, this stimulus was sufficient to induce respiration. Upon examination, oxygen and parenteral fluids were administered, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen. Two hours after 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, were provided. By four hours post-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 after ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional cases involving children weighing approximately 10 kg who accidentally ingested about 120 mg/kg of ibuprofen, no signs of acute intoxication or late sequelae were observed. Notably, one child exhibited a blood level of 700 μg/mL 90 minutes after ingestion, which is approximately ten times the peak levels documented in absorption-excretion studies.

Another case involved a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours. He reported dizziness, and nystagmus was observed. Following hospitalization, he received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

Management Recommendations 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 beneficial. Supportive measures should be prioritized, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant in monitoring patients for potential symptoms and provide appropriate supportive care as needed.

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

In animal studies involving NSAIDs, including ibuprofen, there was an increased incidence of dystocia, delayed parturition, and decreased pup survival observed in rats. 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.

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 is essential to store the product at a controlled room temperature, maintaining a range of 20° to 25°C (68° to 77°F). Proper storage conditions are crucial to ensure the integrity and efficacy of the product.

Additional Clinical Information

Patients on long-term treatment with ibuprofen should have their complete blood count (CBC) and chemistry profile monitored periodically. If any clinical signs or symptoms indicative of liver or renal disease arise, or if systemic manifestations such as eosinophilia or rash occur, ibuprofen should be discontinued, especially if abnormal liver tests persist or worsen.

Before initiating therapy with ibuprofen, patients should be counseled on potential serious cardiovascular risks, 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 gastrointestinal risks, including ulcers and bleeding, and report any signs of these conditions, such as epigastric pain or melena. Additionally, patients should be informed about the risk of serious skin reactions, including exfoliative dermatitis and Stevens-Johnson syndrome (SJS), and instructed to discontinue the medication and contact their physician if a rash develops. Other important counseling points include reporting unexplained weight gain or edema, recognizing signs of hepatotoxicity, and being aware of anaphylactoid reactions. Finally, 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)