Ibu

Description

Ibuprofen tablets 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 of ibuprofen is provided below.

This nonsteroidal anti-inflammatory drug (NSAID) is formulated for oral administration and is available in tablet strengths of 400 mg, 600 mg, and 800 mg. The tablets also contain several inactive ingredients, including carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, polysorbate, and titanium dioxide.

Uses and Indications

Ibuprofen tablets are indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Limitations of Use: Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have not been conducted. Therefore, the use of ibuprofen in pediatric populations should be approached with caution.

Dosage and Administration

The lowest effective dose should be utilized for the shortest duration consistent with individual patient treatment goals. After assessing the response to initial therapy, healthcare professionals should adjust the dose and frequency to meet the specific needs of each patient. The total daily dose must not exceed 3200 mg.

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, administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). The dosage should be individualized, with adjustments made based on the severity of symptoms. It is important to note that patients with rheumatoid arthritis may require higher doses compared to those with osteoarthritis.

In cases of mild to moderate pain, a dosage of 400 mg may be administered every 4 to 6 hours as needed for pain relief. For the treatment of dysmenorrhea, a dosage of 400 mg every 4 hours may be given as necessary for pain relief. If gastrointestinal complaints arise, it is recommended to administer Ibuprofen tablets with meals or milk to mitigate these effects.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of ibuprofen is not recommended for individuals who have a history of asthma, urticaria, or allergic-type reactions following the administration of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been reported in these patients. Furthermore, ibuprofen tablets are contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Pregnant women should be advised to avoid the use of Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) starting at 30 weeks of gestation due to the risk of premature closure of the fetal ductus arteriosus. Clinical trials have indicated an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which may be fatal. The relative increase in serious cardiovascular thrombotic events associated with NSAID use is similar in patients with and without known cardiovascular disease or risk factors; however, those with known cardiovascular disease or risk factors experience a higher absolute incidence of these events.

Patients using NSAIDs, including Ibuprofen, are at an elevated risk for serious gastrointestinal (GI) adverse events, which may include inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, all of which can be fatal. Additionally, NSAIDs can contribute to the onset of new hypertension or exacerbate preexisting hypertension. It is important to note that the use of Ibuprofen may diminish the cardiovascular effects of several therapeutic agents prescribed for heart failure.

Anaphylactoid reactions may occur in patients who have not previously been exposed to Ibuprofen tablets. Serious skin adverse reactions, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, have also been reported. Furthermore, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been documented in patients taking NSAIDs, including Ibuprofen.

Ibuprofen tablets are not intended to replace corticosteroids or to treat corticosteroid insufficiency. The pharmacological effects of Ibuprofen in reducing fever and inflammation may obscure diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions.

Healthcare professionals should monitor patients on long-term NSAID treatment for signs or symptoms of GI bleeding. Regular checks of complete blood count (CBC) and chemistry profiles are recommended for these patients. If any clinical signs or symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, the use of Ibuprofen tablets should be discontinued.

Emergency medical assistance should be sought immediately in the event of an anaphylactoid reaction. Patients should discontinue Ibuprofen tablets at the first sign of a skin rash or any other indication of hypersensitivity. If symptoms consistent with DRESS are observed, Ibuprofen should be discontinued, and the patient should be evaluated without delay.

Side Effects

Patients receiving treatment with this medication may experience a range of adverse reactions. The following sections categorize these reactions based on their seriousness and frequency.

Serious adverse reactions include cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. The risk of these events may increase early in treatment and with prolonged use. Additionally, there is a significant risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal events can occur at any time during treatment and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Common adverse reactions, occurring in greater than 1% but less than 3% of patients, include gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, abdominal distress, and constipation. Central nervous system effects may manifest as dizziness, headache, and nervousness. Dermatologic reactions may include rash (including maculopapular types) and pruritus. Other common reactions involve special senses, such as tinnitus, and metabolic/endocrine issues like decreased appetite. Cardiovascular reactions may present as edema and fluid retention, which generally respond promptly to drug discontinuation.

Adverse reactions with a precise incidence unknown but occurring in less than 1% of patients include more severe gastrointestinal issues such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, and pancreatitis. Central nervous system reactions may include depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Dermatologic reactions may involve vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia. Special senses may be affected by hearing loss and amblyopia. Hematologic reactions can include neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia. Cardiovascular issues may involve congestive heart failure in patients with marginal cardiac function, elevated blood pressure, and palpitations.

Reactions with an unknown causal relationship, also occurring in less than 1% of patients, may include central nervous system effects such as paresthesias, hallucinations, and dream abnormalities. Dermatologic reactions may consist of toxic epidermal necrolysis and photoallergic skin reactions. Special senses may be affected by conjunctivitis, diplopia, optic neuritis, and cataracts. Hematologic issues may present as bleeding episodes. Metabolic/endocrine reactions can include gynecomastia and hypoglycemic reactions. Cardiovascular reactions may involve arrhythmias. Renal issues may manifest as acute renal failure, decreased creatinine clearance, and hematuria. Miscellaneous reactions may include dry eyes and mouth, gingival ulcer, and rhinitis.

Postmarketing experience has revealed additional skin and appendage reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and fixed drug eruption.

Drug Interactions

Concomitant use of certain medications may lead to significant drug interactions that can affect therapeutic outcomes. The following interactions have been identified:

ACE-Inhibitors and NSAIDs Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive efficacy of ACE-inhibitors. Clinicians should consider this interaction when prescribing NSAIDs to patients who are concurrently taking ACE-inhibitors.

Aspirin and Ibuprofen Pharmacodynamic studies indicate that ibuprofen, particularly at a dosage of 400 mg administered three times daily, can interfere with the antiplatelet effects of aspirin. This interaction is observed even when ibuprofen is taken once daily, especially if ibuprofen is dosed prior to aspirin. To mitigate this interaction, it is recommended that immediate-release low-dose aspirin be administered at least 2 hours before a once-daily dose of ibuprofen. However, this timing does not apply to enteric-coated low-dose aspirin.

Due to the potential increased risk of cardiovascular events stemming from ibuprofen's interference with aspirin's antiplatelet effect, healthcare providers should consider alternative analgesics that do not affect aspirin's efficacy, or non-NSAID analgesics, for patients who are on low-dose aspirin for cardiovascular protection.

Additionally, when ibuprofen tablets are taken alongside aspirin, there is a noted reduction in ibuprofen's protein binding; however, the clearance of free ibuprofen remains unchanged. The clinical significance of this interaction is not fully understood, but as with other NSAIDs, the concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

Packaging & NDC

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

Pediatric Use

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

Geriatric Use

Caution should be exercised when treating elderly patients, 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

The use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen, in pregnant patients, particularly after approximately 20 weeks of gestation, is associated with significant fetal risks. Administration of NSAIDs during this period may lead to fetal renal dysfunction, resulting in oligohydramnios, which can occur as early as 48 hours after initiation of treatment. Oligohydramnios is often reversible upon discontinuation of the NSAID; however, prolonged oligohydramnios can lead to serious complications, including limb contractures and delayed lung maturation.

Furthermore, the use of NSAIDs, including Ibuprofen, around 30 weeks of gestation and later is contraindicated due to the increased risk of premature closure of the fetal ductus arteriosus. In some reported cases of impaired neonatal renal function, invasive interventions such as exchange transfusion or dialysis were necessary.

If NSAID treatment is deemed essential between 20 and 30 weeks of gestation, it is recommended to limit Ibuprofen to the lowest effective dose for the shortest duration possible. Healthcare providers should consider ultrasound monitoring of amniotic fluid if Ibuprofen is administered for more than 48 hours. Should oligohydramnios develop, Ibuprofen should be discontinued, and appropriate follow-up should be conducted in accordance with clinical practice guidelines.

Lactation

There are no specific statements regarding the use of this medication in nursing mothers or lactation. Therefore, healthcare professionals should exercise caution when prescribing this medication to lactating mothers, as the effects on breastfed infants and the excretion of the drug in breast milk are not established.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. In patients where renal prostaglandins play a compensatory role in maintaining renal perfusion, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow. This reduction can precipitate overt renal decompensation, particularly in patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.

Due to the lack of controlled clinical study data regarding the use of Ibuprofen tablets in patients with advanced renal disease, treatment with Ibuprofen is not recommended in this population. If initiation of Ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's renal function is advised. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

Hepatic Impairment

Patients with hepatic impairment do not require specific dosage adjustments when receiving this medication. Additionally, there are no special monitoring requirements or precautions indicated for this patient population. It is advisable for healthcare providers to consider the overall clinical context when prescribing to patients with compromised liver function, although the absence of specific recommendations suggests that standard dosing may be appropriate.

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). 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. Initial management included the administration of oxygen and parenteral fluids. Gastric aspiration yielded a greenish-yellow fluid, with no ibuprofen detected. Two hours after ingestion, the child's condition stabilized, although she continued to exhibit periods of apnea lasting 5 to 10 seconds. Following admission to intensive care, sodium bicarbonate, along with dextrose and normal saline infusions, were administered. By four hours post-ingestion, the child was more responsive, able to sit independently and follow verbal commands. A blood level of ibuprofen measured 102.9 mcg/mL approximately 8.5 hours after ingestion, and the child appeared to have fully recovered by the 12-hour mark.

In two additional cases involving children weighing approximately 10 kg who ingested about 120 mg/kg of ibuprofen, no acute intoxication or delayed sequelae were observed. One child exhibited a blood level of 700 mcg/mL 90 minutes after ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies. A separate case involved a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours, presenting with dizziness and nystagmus. After hospitalization, he received parenteral hydration and was placed on bed rest for three days, ultimately recovering without any reported sequelae.

Management Recommendations In instances of acute ibuprofen overdosage, it is recommended to empty the stomach through vomiting or gastric lavage, although the efficacy of this intervention diminishes if more than one hour has passed since ingestion. Given the acidic nature of ibuprofen and its urinary excretion, administering an alkali to induce diuresis may be beneficial. Supportive care is essential, and the use of oral activated charcoal can be considered to mitigate further absorption and reabsorption of the drug.

Healthcare professionals should remain vigilant for potential symptoms of overdosage and implement appropriate management strategies to ensure patient safety and recovery.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen, during pregnancy has been associated with teratogenic effects, particularly concerning the fetal ductus arteriosus and renal function. Specifically, NSAID exposure can lead to premature closure of the fetal ductus arteriosus and fetal renal dysfunction, which may result in oligohydramnios and, in some instances, neonatal renal impairment. It is advised to avoid the use of NSAIDs, including Ibuprofen, in pregnant women at approximately 30 weeks of gestation and later. If NSAID treatment is deemed necessary between approximately 20 weeks and 30 weeks of gestation, it is recommended to limit Ibuprofen use to the lowest effective dose for the shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if Ibuprofen treatment extends beyond 48 hours, and the medication should be discontinued if oligohydramnios occurs, with follow-up according to clinical practice.

Oligohydramnios, while often reversible upon discontinuation of treatment, may lead to complications such as limb contractures and delayed lung maturation if prolonged. In certain postmarketing cases of impaired neonatal renal function, invasive interventions such as exchange transfusion or dialysis were required.

Data from observational studies regarding other potential embryofetal risks associated with NSAID use during the first or second trimesters of pregnancy remain inconclusive. Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, it is important to note that animal reproduction studies do not always predict human responses. Animal data indicate that prostaglandins play a crucial role in endometrial vascular permeability, blastocyst implantation, and decidualization. In studies involving prostaglandin synthesis inhibitors like Ibuprofen, there was an observed increase in pre- and post-implantation loss. Furthermore, prostaglandins are essential for fetal kidney development, and published animal studies have reported that prostaglandin synthesis inhibitors can impair kidney development when administered at clinically relevant doses.

The effects of Ibuprofen tablets on labor and delivery in pregnant women remain unknown. In rat studies involving NSAIDs, similar to other drugs that inhibit prostaglandin synthesis, there was an increased incidence of dystocia, delayed parturition, and decreased pup survival.

Postmarketing Experience

During postapproval use of ibuprofen, the following adverse reactions have been identified. These reactions were reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and appendages-related adverse events include exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as ibuprofen, 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 advised to be vigilant for symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately.

It is important to inform patients that ibuprofen tablets, like other NSAIDs, can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects such as ulcers and bleeding, which may lead to hospitalization or even death. Patients should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they observe any indicative signs or symptoms. The importance of follow-up in this regard should be emphasized.

Patients should also be made aware that ibuprofen tablets can cause serious skin side effects, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization and potentially death. Although serious skin reactions may occur without warning, patients should be vigilant for signs and symptoms of skin reactions, blisters, fever, or other signs of hypersensitivity such as itching. They should be instructed to stop the medication immediately if any type of reaction occurs and to contact their healthcare provider as soon as possible.

Patients should be advised to stop taking ibuprofen tablets immediately if they develop any type of reaction or fever and to contact their healthcare provider promptly.

Additionally, patients should be alert for symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and should contact their healthcare provider if such symptoms occur.

Patients should be informed about the warning signs and symptoms of hepatotoxicity, which may include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms. If these symptoms occur, patients should be instructed to discontinue therapy and seek immediate medical attention.

Patients should also be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. If these symptoms occur, patients should be instructed to seek immediate emergency help.

In late pregnancy, ibuprofen tablets should be avoided, as with other NSAIDs, due to the risk of premature closure of the ductus arteriosus. Pregnant women should be informed to avoid the use of ibuprofen and other NSAIDs starting at 30 weeks gestation. If treatment with ibuprofen is necessary for a pregnant woman between approximately 20 to 30 weeks gestation, she should be advised that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

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 room temperature, ensuring that the storage environment does not exceed excessive heat above 40°C (104°F). Proper handling should be observed to maintain the integrity of the product during storage.

Additional Clinical Information

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as there is a risk of serious GI tract ulcerations and bleeding associated with the use of NSAIDs. For patients undergoing long-term treatment with NSAIDs, it is recommended that complete blood counts (CBC) and chemistry profiles be checked periodically to assess for potential adverse effects.

In cases where patients exhibit clinical signs and symptoms indicative of liver or renal disease, or if systemic manifestations such as eosinophilia occur, Ibuprofen tablets should be discontinued. Additionally, if abnormal liver tests persist or worsen, immediate cessation of the medication is advised.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Ibu as submitted by Dr. Reddy's Laboratories Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)