Ibuprofen

Description

Ibuprofen tablets, USP contain the active ingredient ibuprofen, which is (±) - 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 (<1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone. The tablets are available in strengths of 300 mg, 400 mg, 600 mg, and 800 mg for oral administration. Inactive ingredients include colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polyethylene glycol, sodium starch glycoate, stearic acid, talc, 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

Healthcare professionals should carefully consider the potential benefits and risks of Ibuprofen Tablets, USP, along with other treatment options, before initiating therapy. It is recommended to use the lowest effective dose for the shortest duration that aligns with individual patient treatment goals.

After assessing the response to initial therapy with Ibuprofen Tablets, USP, 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, it is advisable to administer Ibuprofen tablets 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, administered 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.

It is noted that 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.

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

Contraindications

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

Caution is advised when considering ibuprofen for patients with preexisting asthma, particularly those with aspirin-sensitive asthma.

Warnings and Precautions

Cardiovascular thrombotic events, including myocardial infarction and stroke, may occur with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), with the risk increasing with prolonged use. Ibuprofen is contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery due to the heightened risk of such events.

NSAIDs, including Ibuprofen, are associated with serious gastrointestinal (GI) adverse events, which can include bleeding, ulceration, and perforation, potentially leading to fatal outcomes. Anaphylactoid reactions may occur even in patients without prior exposure to Ibuprofen; immediate emergency medical assistance should be sought if such reactions arise. Additionally, serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported and can be fatal. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has also been documented and can be life-threatening; Ibuprofen should be discontinued if any symptoms of DRESS occur.

In pregnant women, the use of NSAIDs around 30 weeks of gestation and later increases the risk of premature closure of the fetal ductus arteriosus. Furthermore, the use of NSAIDs at approximately 20 weeks of gestation or later may lead to fetal renal dysfunction, resulting in oligohydramnios and potential neonatal renal impairment.

Ibuprofen is not a substitute for corticosteroids and cannot treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of the underlying disease. For patients on long-term NSAID therapy, it is recommended to monitor hemoglobin or hematocrit levels if signs of anemia are present. Caution is advised in patients with asthma, as those with aspirin-sensitive asthma should not receive Ibuprofen.

Monitoring for signs or symptoms of GI bleeding is essential in patients receiving long-term NSAID treatment. Periodic checks of complete blood count (CBC) and chemistry profiles are also advised for these patients. Ibuprofen should be discontinued if clinical signs of liver or renal disease develop, or if abnormal liver tests persist or worsen.

Emergency medical help should be sought in the event of an anaphylactoid reaction. Patients should discontinue Ibuprofen at the first sign of a skin rash or any other indication of hypersensitivity. If symptoms consistent with meningitis develop, the possibility of a relationship to Ibuprofen should be considered. Additionally, if clinical signs and symptoms indicative of liver disease occur, Ibuprofen should be stopped immediately.

Side Effects

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

Serious adverse reactions include cardiovascular thrombotic events such as myocardial infarction and stroke, which can be fatal. These events may occur early in treatment and the risk may increase with prolonged use. Additionally, there is an increased 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, often without warning symptoms, and elderly patients are at a higher risk. Patients undergoing coronary artery bypass graft (CABG) surgery should not use ibuprofen tablets due to contraindications related to these risks.

Common gastrointestinal adverse reactions reported include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal issues may involve nausea and vomiting, indigestion, constipation, abdominal cramps or pain, and fullness of the gastrointestinal tract, such as bloating or flatulence. Serious gastrointestinal complications may include gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis.

Central nervous system reactions may manifest as dizziness, headache, and nervousness. Other reported symptoms include depression, insomnia, confusion, emotional liability, somnolence, and in rare cases, aseptic meningitis with fever and coma. Additional central nervous system effects may include paresthesias, hallucinations, dream abnormalities, and pseudotumor cerebri.

Dermatologic reactions can range from common rashes, including maculopapular types and pruritus, to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia. Serious skin reactions may also include toxic epidermal necrolysis and photoallergic skin reactions.

Adverse reactions affecting special senses include tinnitus, hearing loss, amblyopia (blurred and/or diminished vision), conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic adverse reactions may involve neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), and thrombocytopenia with or without purpura. Patients may also experience bleeding episodes such as epistaxis and menorrhagia.

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

Cardiovascular reactions may present as edema and fluid retention, which generally respond promptly to drug discontinuation. Other cardiovascular issues may include congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (sinus tachycardia and sinus bradycardia).

Allergic reactions can manifest as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Other allergic conditions may 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 adverse reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

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

Drug Interactions

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents, particularly ACE inhibitors, may result in diminished antihypertensive efficacy. It is advisable to monitor blood pressure closely in patients receiving this combination.

Ibuprofen has been shown to interfere with the antiplatelet effects of aspirin, particularly when ibuprofen is administered prior to aspirin. To mitigate this interaction, it is recommended that immediate-release low-dose aspirin be taken at least 2 hours before ibuprofen. Due to the potential for increased adverse effects, the concurrent use of ibuprofen and aspirin is generally not recommended.

The natriuretic effect of diuretics such as furosemide and thiazides may be reduced by ibuprofen, which is attributed to its inhibition of renal prostaglandin synthesis. Clinicians should consider monitoring the effectiveness of diuretic therapy in patients taking ibuprofen.

In patients receiving lithium therapy, ibuprofen can elevate plasma lithium levels and decrease renal clearance, thereby increasing the risk of lithium toxicity. Regular monitoring of lithium levels is recommended in such cases.

The use of NSAIDs may enhance the toxicity of methotrexate by competitively inhibiting its renal accumulation. Caution should be exercised when these medications are co-administered, and appropriate monitoring of methotrexate levels may be warranted.

When prescribing ibuprofen to patients on warfarin-type anticoagulants, caution is advised due to the increased risk of serious gastrointestinal bleeding. Close monitoring for signs of bleeding is recommended.

Co-administration of cimetidine or ranitidine with ibuprofen does not significantly alter ibuprofen serum concentrations, and no dosage adjustments are necessary in this context.

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 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 (65 years and older) with this medication, as with any nonsteroidal anti-inflammatory drugs (NSAIDs). It is important for healthcare providers to closely monitor this population for potential adverse effects and to consider appropriate dosage adjustments based on individual patient needs and responses.

Pregnancy

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, during pregnancy is associated with significant risks, particularly when used after approximately 20 weeks of gestation. The use of NSAIDs at about 30 weeks gestation or later can lead to premature closure of the fetal ductus arteriosus, which is a critical vessel for fetal circulation. Additionally, NSAID use during this period has been linked to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment.

Healthcare professionals are advised to limit the dose and duration of Ibuprofen tablets use between approximately 20 and 30 weeks of gestation. If NSAID treatment is deemed necessary after 20 weeks, it should be restricted to the lowest effective dose for the shortest duration possible. Monitoring with ultrasound for oligohydramnios is recommended if treatment extends beyond 48 hours. Should oligohydramnios occur, discontinuation of Ibuprofen tablets is warranted, followed by appropriate clinical follow-up.

Data from observational studies regarding the risks of NSAID use during the first and second trimesters are inconclusive. While animal reproduction studies in rats and rabbits have not shown developmental abnormalities, these findings may not be predictive of human outcomes. Prostaglandins, which are inhibited by NSAIDs like Ibuprofen, play a crucial role in various reproductive processes, including endometrial vascular permeability and fetal kidney development. Animal studies have indicated that the use of prostaglandin synthesis inhibitors can lead to increased pre- and post-implantation loss and may impair kidney development at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2 to 4% and 15 to 20%, respectively. However, the specific background risk associated with Ibuprofen tablets remains unknown. There are no adequate, well-controlled studies in pregnant women, and the use of Ibuprofen tablets should only occur if the potential benefits justify the potential risks to the fetus.

Published literature indicates that adverse outcomes, such as fetal renal dysfunction leading to oligohydramnios, may occur after days to weeks of NSAID treatment, although some cases of oligohydramnios have been reported as soon as 48 hours after initiation. While many instances of decreased amniotic fluid have been transient and reversible upon cessation of the drug, there are reports of irreversible neonatal renal dysfunction requiring invasive interventions.

Due to methodological limitations in postmarketing studies, including the absence of control groups and limited data on dosing and timing, establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use remains challenging. Consequently, the generalizability of reported risks to full-term infants exposed to NSAIDs through maternal use is uncertain.

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 breastfeeding 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; therefore, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, subsequently, renal blood flow. This can precipitate overt renal decompensation, particularly in patients at greatest risk, including those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.

Discontinuation of NSAID therapy typically results in recovery to the pretreatment state. However, there is no available information from controlled clinical studies regarding the use of Ibuprofen tablets in patients with advanced renal disease, and treatment with Ibuprofen tablets is not recommended in this population. If initiation of Ibuprofen tablet therapy is deemed necessary, close monitoring of renal function is advised.

Additionally, the use of NSAIDs, including Ibuprofen tablets, during pregnancy, particularly around 20 weeks gestation or later, may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes may occur after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after initiation. If NSAID treatment is required between 20 and 30 weeks of gestation, it is recommended to limit the use of Ibuprofen tablets to the lowest effective dose and shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if treatment extends beyond 48 hours, and Ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up according to clinical practice.

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 patient's age and weight.

A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg). This child presented with apneic and cyanotic symptoms, necessitating oxygen and fluid administration. Blood analysis approximately 8½ hours post-ingestion revealed a concentration of 102.9 mcg/mL.

Conversely, two separate cases involving children weighing around 10 kg who ingested approximately 120 mg/kg of ibuprofen showed no acute signs of intoxication. Notably, one child's blood level was measured at 700 mcg/mL just 90 minutes after ingestion, indicating that significant variability in response can occur.

In an adult case, a 19-year-old male ingested 8,000 mg of ibuprofen over a few hours, resulting in dizziness. Fortunately, he recovered following hospitalization and hydration, with no lasting effects.

For the management of acute ibuprofen overdosage, it is critical to empty the stomach through vomiting or gastric lavage within one hour of ingestion, as little drug will likely be recovered after this timeframe. The administration of alkali and the induction of diuresis may be beneficial due to the acidic nature of ibuprofen and its urinary excretion. Additionally, oral activated charcoal can be utilized to help reduce absorption of the drug.

Supportive measures are paramount in the management of overdose cases. Continuous monitoring for signs of toxicity is essential, and healthcare professionals should provide appropriate care based on the clinical presentation of the patient.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, during pregnancy has been associated with teratogenic effects, particularly when administered around 30 weeks of gestation or later. The literature indicates that NSAID use at this stage may lead to premature closure of the fetal ductus arteriosus. Additionally, administration of NSAIDs from approximately 20 weeks of gestation onward has been linked to fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment.

In animal studies, the administration of prostaglandin synthesis inhibitors, such as Ibuprofen, has demonstrated an increase in pre- and post-implantation loss. Prostaglandins are critical for fetal kidney development, and evidence from animal studies suggests that the use of prostaglandin synthesis inhibitors at clinically relevant doses can impair kidney development.

While reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities, it is important to note that animal reproduction studies may not always predict human responses. Therefore, caution is advised regarding the use of NSAIDs in pregnant women, particularly after 30 weeks of gestation. If NSAID treatment is deemed necessary between 20 and 30 weeks of gestation, it is recommended to limit the use of Ibuprofen tablets to the lowest effective dose for the shortest duration possible.

Oligohydramnios, a potential consequence of NSAID use, is often reversible upon discontinuation of treatment; however, prolonged oligohydramnios may lead to complications such as limb contractures and delayed lung maturation.

Postmarketing Experience

During postapproval use of ibuprofen, the following adverse reactions have been identified through voluntary reports and surveillance programs: exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE). These events were reported in the context of routine pharmacovigilance activities.

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as Ibuprofen tablets, and periodically throughout the course of treatment. It is important to encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients to be vigilant for symptoms of cardiovascular thrombotic events, which may include chest pain, shortness of breath, weakness, or slurring of speech. Patients should be instructed to report any of these symptoms to their healthcare provider immediately.

Patients should be made aware 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. Although serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for signs and symptoms indicative of these conditions, including epigastric pain, dyspepsia, melena, and hematemesis. The importance of seeking medical advice upon observing any of these signs or symptoms should be emphasized.

Healthcare providers should also inform patients about the risk of serious skin reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients should be advised to discontinue Ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

Patients should be alerted to the symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and should be instructed to contact their healthcare provider if such symptoms occur.

It is crucial to inform patients 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 stop therapy and seek immediate medical attention.

Patients should also be educated on the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. In the event of these symptoms, patients should be instructed to seek immediate emergency help.

In late pregnancy, as with other NSAIDs, Ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus. Pregnant women should be informed to avoid the use of Ibuprofen tablets and other NSAIDs starting at 30 weeks gestation. If treatment with Ibuprofen tablets 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 a tight, light-resistant container as defined by the United States Pharmacopeia (USP). It is essential to store the product at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Care should be taken to avoid exposure to excessive heat, specifically temperatures exceeding 40°C (104°F).

Additional Clinical Information

Clinicians are advised to monitor patients for signs or symptoms of gastrointestinal (GI) bleeding during treatment. For patients undergoing long-term therapy with nonsteroidal anti-inflammatory drugs (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, such as eosinophilia or rash, or if abnormal liver tests persist or worsen, it is imperative that Ibuprofen tablets be discontinued promptly.

FDA Insert (PDF)

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

View full prescribing information (PDF)