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. Ibuprofen is available in 300 mg, 400 mg, 600 mg, and 800 mg tablets for oral administration. Inactive ingredients include colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium starch glycoate, stearic acid, talc, and titanium dioxide.

Uses and Indications

Ibuprofen tablets 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 in pediatric populations have not been conducted. Therefore, healthcare professionals should exercise caution when considering the use of ibuprofen in children.

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 are advised to adjust the dose and frequency to meet the specific needs of the patient. The total daily dose must not exceed 3200 mg. In cases where gastrointestinal complaints arise, it is recommended to administer Ibuprofen tablets with meals or milk.

For the management of rheumatoid arthritis and osteoarthritis, the suggested dosage ranges from 1200 mg to 3200 mg daily, which can be administered as 400 mg, 600 mg, or 800 mg three times a day (tid) or four times a day (qid).

For the treatment of mild to moderate pain, a dosage of 400 mg may be given every 4 to 6 hours as necessary for pain relief. In the case of dysmenorrhea, a dosage of 400 mg can be administered every 4 hours as needed for pain 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

Nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen tablets, are associated with an increased risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is likely to escalate with prolonged use. Ibuprofen tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

Patients with known cardiovascular disease or risk factors are at a higher absolute incidence of serious cardiovascular thrombotic events. Therefore, the use of Ibuprofen tablets in patients with a recent myocardial infarction should be approached with caution, weighing the benefits against the risk of recurrent cardiovascular events. If Ibuprofen is administered, it is imperative to monitor patients for signs of cardiac ischemia.

NSAIDs can also lead to serious gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, which can be fatal. These events may occur at any time, with or without warning symptoms. Physicians should remain vigilant for signs or symptoms of GI bleeding in patients on long-term NSAID therapy.

Additionally, NSAIDs, including Ibuprofen tablets, may cause new-onset hypertension or exacerbate preexisting hypertension. The use of Ibuprofen tablets in patients with severe heart failure should be avoided unless the potential benefits outweigh the risks of worsening heart failure. If used, patients should be monitored for signs of heart failure deterioration.

Anaphylactoid reactions can occur in patients without prior exposure to Ibuprofen tablets, necessitating immediate emergency medical assistance in such cases. Serious skin adverse reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported. Discontinuation of Ibuprofen tablets is advised at the first sign of a skin rash or any other hypersensitivity indication.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has also been documented in patients taking NSAIDs like Ibuprofen. If any signs or symptoms of DRESS are observed, Ibuprofen tablets should be discontinued, and the patient should be evaluated promptly. Furthermore, the use of NSAIDs, including Ibuprofen tablets, is contraindicated in pregnant women at approximately 30 weeks gestation and later due to the risk of premature closure of the fetal ductus arteriosus.

Ibuprofen tablets are not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of the underlying condition. For patients on long-term NSAID therapy, it is recommended to periodically check hemoglobin or hematocrit levels, especially if any signs or symptoms of anemia arise.

Laboratory monitoring is essential for patients receiving long-term NSAID treatment. A complete blood count (CBC) and chemistry profile should be assessed periodically. If clinical signs or symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, Ibuprofen tablets should be discontinued.

In summary, healthcare professionals should exercise caution when prescribing Ibuprofen tablets, ensuring appropriate monitoring and patient education regarding potential adverse effects and the need for immediate medical attention in the event of serious reactions.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication, categorized by seriousness and frequency.

Serious adverse reactions include an increased risk of cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is known to escalate with prolonged use. Additionally, there is a significant risk of serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal complications can occur at any time during treatment, often without warning symptoms, and elderly patients are particularly vulnerable.

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 a sensation of fullness in the gastrointestinal tract, such as bloating or flatulence. More severe gastrointestinal reactions, such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis, have also been observed.

Central nervous system reactions may include dizziness, headache, and nervousness. More serious effects can involve depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis, which may present with fever and coma. Other reported symptoms include paresthesias, hallucinations, dream abnormalities, and pseudotumor cerebri.

Dermatologic reactions range from rash (including maculopapular types) and pruritus to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia. Serious skin reactions like toxic epidermal necrolysis and photoallergic skin reactions have also been noted.

Adverse reactions affecting the special senses include tinnitus, hearing loss, amblyopia (blurred and/or diminished vision), scotomata, and changes in color vision. Other reported issues involve conjunctivitis, diplopia, and optic neuritis, with cataracts also being a concern.

Hematologic adverse reactions can include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), and thrombocytopenia with or without purpura. Patients may also experience eosinophilia and decreases in hemoglobin and hematocrit, along with bleeding episodes such as epistaxis and menorrhagia.

Metabolic and endocrine reactions may manifest as decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis. Cardiovascular reactions can include edema, fluid retention (which generally responds promptly to drug discontinuation), congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (such as sinus tachycardia and sinus bradycardia).

Allergic reactions may present as a syndrome characterized by abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Other allergic conditions reported include serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis, and angioedema.

Renal adverse reactions can include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, and hematuria, with renal papillary necrosis also being a noted concern.

Miscellaneous adverse reactions may involve dry eyes and mouth, gingival ulcer, and rhinitis.

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

Drug Interactions

The co-administration of certain medications can lead to significant drug interactions that may affect therapeutic outcomes and safety.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs, including ibuprofen, may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors. Clinicians should monitor blood pressure and consider dosage adjustments of the antihypertensive agent as necessary.

When ibuprofen is taken concurrently with aspirin, it can interfere with the antiplatelet activity of aspirin, particularly if ibuprofen is administered prior to aspirin. It is advisable to space the administration of these medications to mitigate this interaction.

Ibuprofen may also reduce the natriuretic effect of diuretics such as furosemide and thiazides. Close monitoring for signs of renal failure is recommended in patients receiving this combination.

Additionally, ibuprofen can elevate plasma lithium levels and decrease the renal clearance of lithium, which increases the risk of lithium toxicity. Regular monitoring of lithium levels is warranted in patients taking both medications.

NSAIDs may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is advised when these drugs are used together, and monitoring for signs of methotrexate toxicity should be implemented.

Anticoagulants

Caution is advised when using ibuprofen in conjunction with warfarin-type anticoagulants due to an increased risk of serious gastrointestinal bleeding. Regular monitoring of coagulation parameters is recommended to ensure patient safety.

H2-Receptor Antagonists

The co-administration of cimetidine or ranitidine with ibuprofen does not significantly affect the serum concentrations of ibuprofen. Therefore, no dosage adjustments are necessary when these medications are used together.

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 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 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

Use of NSAIDs, including Ibuprofen tablets, during pregnancy is associated with significant risks, particularly when administered around 20 to 30 weeks of gestation. The use of these medications can lead to premature closure of the fetal ductus arteriosus and fetal renal dysfunction, which may result in oligohydramnios and, in some cases, neonatal renal impairment. Therefore, it is recommended to limit the dose and duration of Ibuprofen tablets use between approximately 20 and 30 weeks of gestation, and to avoid their use at around 30 weeks of gestation and later in pregnancy.

Observational studies have indicated that the use of NSAIDs at about 30 weeks gestation or later increases the risk of premature closure of the fetal ductus arteriosus. Additionally, the use of NSAIDs at about 20 weeks gestation or later has been linked to fetal renal dysfunction leading to oligohydramnios, with some instances of neonatal renal impairment reported. These adverse outcomes typically occur after days to weeks of treatment, although oligohydramnios has been infrequently observed as soon as 48 hours after initiation of NSAID therapy. While many cases of decreased amniotic fluid have been transient and reversible upon cessation of the drug, there have been limited reports of irreversible neonatal renal dysfunction requiring invasive interventions.

Data from animal studies have shown that prostaglandins play a crucial role in fetal kidney development and that the administration of prostaglandin synthesis inhibitors, such as Ibuprofen, can impair kidney development at clinically relevant doses. Although reproductive studies in rats and rabbits have not demonstrated developmental abnormalities, animal reproduction studies are not always predictive of human response. The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2-4% and 15-20%, respectively; however, the specific background risk associated with Ibuprofen tablets remains unknown.

There are no adequate, well-controlled studies in pregnant women, and Ibuprofen tablets should only be used during pregnancy if the potential benefits justify the potential risks to the fetus. If NSAID treatment is deemed necessary at about 20 weeks gestation or later, it is advised to limit the use to the lowest effective dose for the shortest duration possible. If treatment extends beyond 48 hours, monitoring with ultrasound for oligohydramnios should be considered. In the event that oligohydramnios occurs, Ibuprofen tablets should be discontinued, and follow-up should be conducted according to clinical practice.

The effects of Ibuprofen tablets on labor and delivery in pregnant women are not well understood, and methodological limitations in postmarketing studies, including the lack of control groups and limited information on dosing and timing, hinder the establishment of a reliable estimate of the risk of adverse fetal and neonatal outcomes. Consequently, healthcare professionals should exercise caution when prescribing Ibuprofen tablets to pregnant patients, particularly during the later stages of pregnancy.

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 may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and precipitate overt renal decompensation.

Patients at the highest risk for these adverse reactions 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 initiation of Ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's 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 NSAID initiation. While oligohydramnios is often reversible upon treatment discontinuation, if NSAID treatment is required between 20 and 30 weeks 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 may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs, including Ibuprofen tablets. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a critical role in maintaining renal perfusion. In patients with compromised liver function, the administration of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate renal decompensation.

Due to the lack of controlled clinical study data regarding the use of Ibuprofen tablets in patients with advanced renal disease, treatment with these tablets is not recommended for this population. If therapy with Ibuprofen tablets is deemed necessary, it is essential to closely monitor renal function throughout the treatment period.

Patients with hepatic impairment should be evaluated for their overall health status, and any potential risks associated with NSAID therapy should be carefully considered. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of vigilant monitoring and assessment in this patient population.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the patient's age and weight.

Clinical Presentation and Symptoms A notable case involved a 19-month-old child who ingested 7 to 10 ibuprofen tablets (400 mg). This child presented with apneic and cyanotic episodes, necessitating oxygen and fluid administration. Stabilization occurred after approximately 2 hours, although the child experienced intermittent apnea lasting 5 to 10 seconds. Blood levels of ibuprofen measured 102.9 mcg/mL around 8½ hours post-ingestion, with the child appearing fully recovered by 12 hours after the event.

In another instance, two children weighing approximately 10 kg each ingested about 120 mg/kg of ibuprofen. These cases did not exhibit any signs of acute intoxication or subsequent complications. Additionally, a 19-year-old male who consumed 8,000 mg of ibuprofen over several hours experienced dizziness but recovered fully after hospitalization and bed rest, with no lasting effects.

Management of Overdosage In the event of acute ibuprofen overdosage, it is critical to initiate decontamination measures promptly. The stomach should be emptied through vomiting or gastric lavage within 1 hour of ingestion, as the likelihood of recovering the drug diminishes significantly after this period.

The administration of oral activated charcoal may be beneficial in reducing both the absorption and reabsorption of ibuprofen. Furthermore, due to the drug's acidic properties, administering alkali and inducing diuresis may enhance urinary excretion, potentially aiding in the management of the overdose.

Healthcare professionals should remain vigilant for symptoms and provide supportive care as necessary, monitoring the patient closely for any signs of complications.

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 use of these medications 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. Notably, fetal renal dysfunction may occur when NSAIDs are used from approximately 20 weeks of gestation onward, with adverse outcomes typically observed after days to weeks of treatment; however, oligohydramnios has been infrequently reported as early as 48 hours following the initiation of NSAID therapy.

In animal studies, the administration of prostaglandin synthesis inhibitors, such as Ibuprofen, has resulted in increased pre- and post-implantation loss. Prostaglandins play a critical role in fetal kidney development, and evidence from published animal studies indicates that the use of prostaglandin synthesis inhibitors can impair kidney development when given at clinically relevant doses.

There are no adequate, well-controlled studies in pregnant women regarding the use of Ibuprofen tablets. Therefore, these medications should only be utilized during pregnancy if the potential benefits outweigh the potential risks to the fetus. The estimated background risk of major birth defects and miscarriage in the general population remains unknown, although all pregnancies carry a baseline risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2-4% and 15-20%, respectively.

Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, it is important to note that animal reproduction studies are not always predictive of human responses.

Postmarketing Experience

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

In the category of skin and appendages, the following events have been documented: exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Patient Counseling

Patients should be informed of the symptoms associated with cardiovascular thrombotic events, which include chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to report any of these symptoms to their healthcare provider immediately.

Healthcare providers should discuss the potential gastrointestinal side effects of Ibuprofen tablets with patients. Patients should be made aware that gastrointestinal discomfort can occur, and in rare cases, serious gastrointestinal side effects such as ulcers and bleeding may arise, potentially leading to hospitalization or death. Patients should be vigilant for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if these symptoms occur.

Patients should be instructed to discontinue the use of Ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

It is important for patients to be alert for symptoms of congestive heart failure, which may include shortness of breath, unexplained weight gain, or edema. They should be advised to contact their healthcare provider if they experience any of these symptoms.

Patients should also 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 stop therapy and seek immediate medical attention.

Healthcare providers should educate patients on the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. Patients should be instructed to seek immediate emergency help if these symptoms occur.

In discussions regarding pregnancy, healthcare providers should inform patients that Ibuprofen tablets should be avoided in late pregnancy due to the risk of premature closure of the ductus arteriosus. Pregnant women should be advised 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 informed that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature. It is essential to avoid exposure to excessive heat, specifically temperatures exceeding 40°C (104°F), to maintain product integrity. Proper storage conditions are crucial for ensuring the efficacy and safety of the product.

Additional Clinical Information

Clinicians are advised to monitor patients for any signs or symptoms indicative 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 assessed periodically to ensure safety and efficacy.

In cases where patients exhibit clinical signs and symptoms suggestive of liver or renal disease, or if systemic manifestations such as eosinophilia or rash occur, it is crucial to discontinue the use of Ibuprofen tablets. Additionally, if abnormal liver function tests persist or worsen, discontinuation of the medication is warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)