Ibuprofen

Description

Ibuprofen Tablets, USP contain the active ingredient ibuprofen, which is chemically designated as (±)-2-(p-isobutylphenyl) propionic acid. Ibuprofen appears as a white powder with a melting point ranging from 74° to 77° C. It exhibits very slight solubility in water, quantified at less than 1 mg/mL, while demonstrating ready solubility in organic solvents such as ethanol and acetone. These tablets are classified as a nonsteroidal anti-inflammatory drug (NSAID) and are available in dosages of 400 mg, 600 mg, and 800 mg for oral administration. The formulation includes several inactive ingredients: 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 are indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. This medication is also 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 this medication in pediatric populations is not recommended.

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, administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). Individual patient responses may vary, with some patients experiencing better outcomes at a total daily dose of 3200 mg compared to 2400 mg. Dosing should be tailored to each patient and adjusted based on the severity of symptoms.

For the management 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 a dose of 400 mg every 4 hours as necessary for pain relief.

It is important not to exceed a total daily dose of 3200 mg. In instances where gastrointestinal complaints arise, ibuprofen tablets should be taken with meals or milk to mitigate discomfort.

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 other 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 should not be administered in the context of coronary artery bypass graft (CABG) surgery.

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.

NSAIDs can also lead to severe gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which may be fatal. These serious adverse events can occur at any time during treatment, with or without warning symptoms.

To mitigate the risk of adverse cardiovascular events in patients treated with NSAIDs, it is recommended to use the lowest effective dose for the shortest duration possible. Blood pressure (BP) should be closely monitored during the initiation of NSAID therapy and throughout the treatment course in patients with hypertension.

Ibuprofen tablets should be avoided in patients with a recent myocardial infarction unless the anticipated benefits outweigh the risks of recurrent cardiovascular thrombotic events. Patients should be monitored for signs of cardiac ischemia. Similarly, the use of ibuprofen tablets in patients with severe heart failure should be approached with caution, and only if the benefits are expected to outweigh the risks of exacerbating heart failure. Monitoring for signs of worsening heart failure is essential in these cases.

Prescribing NSAIDs requires extreme caution in individuals with a history of ulcer disease or gastrointestinal bleeding due to the heightened risk of serious GI complications.

In patients with advanced renal disease, close monitoring of renal function is advisable if ibuprofen therapy is deemed necessary.

Healthcare professionals should instruct patients to seek emergency medical assistance if an anaphylactoid reaction occurs. Patients should also be educated on the signs and symptoms of serious skin reactions, advising them to discontinue ibuprofen tablets at the first appearance of a skin rash or any other indication of hypersensitivity. If symptoms indicative of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) arise, ibuprofen tablets should be discontinued immediately, and the patient should be evaluated without delay.

Side Effects

Patients receiving the medication may experience a range of adverse reactions. 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 increase 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 include dizziness, headache, and nervousness. Dermatologic reactions such as rash (including maculopapular types) and pruritus have also been reported. Other common reactions include tinnitus, decreased appetite, and cardiovascular issues like edema and fluid retention, which generally respond promptly to discontinuation of the drug.

Less common adverse reactions, with a precise incidence unknown but occurring in less than 1% of patients, may include serious gastrointestinal complications such as gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis. Central nervous system effects may also include depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Dermatologic reactions can be severe, including vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia. Hematologic reactions such as neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia have been observed, along with renal issues like acute renal failure and hematuria.

There are also adverse reactions with an unknown causal relationship, including central nervous system effects such as paresthesias, hallucinations, and dream abnormalities. Special senses may be affected, leading to hearing loss and visual disturbances. Cardiovascular reactions may include congestive heart failure in patients with marginal cardiac function, elevated blood pressure, and arrhythmias. Allergic reactions can manifest as abdominal pain, fever, chills, nausea, vomiting, anaphylaxis, and angioedema. Renal complications such as renal papillary necrosis have also been reported.

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

Drug Interactions

Concomitant use of certain medications with ibuprofen may lead to significant drug interactions, categorized primarily into pharmacodynamic and pharmacokinetic interactions.

Pharmacodynamic Interactions

ACE-Inhibitors Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may reduce the antihypertensive effect of ACE-inhibitors. Clinicians should consider this interaction in patients receiving both medications.

Aspirin Ibuprofen has been shown to interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered before aspirin. This interaction is evident even with a once-daily regimen of ibuprofen at 400 mg. To mitigate this risk, it is advisable to administer immediate-release low-dose aspirin at least 2 hours prior to ibuprofen. However, this timing does not apply to enteric-coated low-dose aspirin. Given the potential for increased cardiovascular events due to this interaction, alternative analgesics that do not affect aspirin's antiplatelet effect should be considered for patients taking low-dose aspirin for cardioprotection.

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 NSAID therapy should be monitored closely for signs of renal failure and to ensure the efficacy of diuretics.

Lithium The co-administration of ibuprofen has been associated with increased plasma lithium levels and decreased renal clearance of lithium. Specifically, a study indicated a 15% increase in mean minimum lithium concentration and a 19% reduction in renal clearance. Careful monitoring for signs of lithium toxicity is recommended when these drugs are used together.

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

Warfarin-type Anticoagulants While short-term studies have not demonstrated significant effects of ibuprofen on prothrombin times in patients on coumarin-type anticoagulants, there is a documented risk of bleeding when these medications are used together. The combined use of warfarin and NSAIDs may increase the risk of serious gastrointestinal bleeding. Physicians should exercise caution when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

H-2 Antagonists Co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine has not shown any significant impact on ibuprofen serum concentrations, indicating that these interactions are not clinically relevant.

In summary, careful consideration and monitoring are warranted when ibuprofen is used in conjunction with the aforementioned drug classes to mitigate potential adverse effects and ensure therapeutic efficacy.

Packaging & NDC

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

Pediatric Use

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

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. Regular monitoring for adverse effects and therapeutic efficacy is recommended to mitigate risks associated with medication use in this age group.

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 administration of NSAIDs at about 30 weeks gestation or later can lead to premature closure of the fetal ductus arteriosus, which may result in serious fetal complications. Additionally, NSAID use during this period has been linked to fetal renal dysfunction, leading to oligohydramnios and, in some cases, neonatal renal impairment.

Due to these risks, it is recommended that the use of ibuprofen tablets be limited in dose and duration between 20 and 30 weeks of gestation, and avoided entirely after 30 weeks. If NSAID treatment is deemed necessary after 20 weeks, it should be restricted to the lowest effective dose for the shortest duration possible. Should treatment with ibuprofen tablets extend beyond 48 hours, monitoring with ultrasound for oligohydramnios is advised. If oligohydramnios is detected, discontinuation of ibuprofen tablets should occur, followed by appropriate clinical follow-up.

While reproductive studies in rats and rabbits have not shown evidence of developmental abnormalities, the predictive value of animal studies for human outcomes is limited. Prostaglandins play a crucial role in various reproductive processes, and their inhibition by NSAIDs has been associated with increased pre- and post-implantation loss in animal studies. Furthermore, there is evidence that prostaglandin synthesis inhibitors can impair fetal kidney development when administered 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 ibuprofen tablets should only be used during pregnancy if the potential benefits justify the potential risks to the fetus.

Published literature indicates that adverse outcomes, such as fetal renal dysfunction and oligohydramnios, may occur after days to weeks of NSAID treatment, although oligohydramnios has been reported as early as 48 hours post-initiation. In some cases, the decrease in amniotic fluid was transient and reversible upon cessation of the drug, while other cases of neonatal renal dysfunction required invasive interventions. The methodological limitations of existing studies, including the lack of control groups and limited data on dosing and timing, hinder the ability to establish a reliable estimate of the risks associated with maternal NSAID use.

The effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown, and caution is warranted when considering NSAID use in this population.

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; 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 therapy with ibuprofen tablets 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 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. 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.

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. Therefore, it is crucial to exercise caution when considering NSAID therapy in this population.

Currently, there is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Consequently, treatment with ibuprofen tablets is not recommended for these patients. If therapy with ibuprofen tablets is deemed necessary, close monitoring of renal function is advised to mitigate the risk of renal complications. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of careful patient management.

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 1½ hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli, which was sufficient to induce respiration. Initial management included the administration of oxygen and parenteral fluids. Gastric aspiration yielded a greenish-yellow fluid, with no evidence of ibuprofen detected. 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. 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 alert, able to sit independently, and responsive to verbal commands. A blood level of ibuprofen measured 102.9 mcg/mL approximately 8½ 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 ingested about 120 mg/kg, no acute intoxication or late sequelae were observed. One child exhibited a blood level of 700 mcg/mL 90 minutes post-ingestion, approximately ten times the peak levels noted in absorption-excretion studies.

Management of Overdosage For adults, a case involving a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours presented with dizziness and nystagmus. After hospitalization, he received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

In instances of acute overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage; however, if more than one hour has passed since ingestion, the likelihood of recovering significant amounts of the drug diminishes. Given the acidic nature of ibuprofen and its urinary excretion, administering alkali and inducing diuresis may be beneficial. Supportive measures should be complemented by the use of oral activated charcoal, which can aid in reducing both the absorption and reabsorption of ibuprofen tablets.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy has been associated with teratogenic effects. Specifically, administration around 30 weeks gestation or later may increase the risk of premature closure of the fetal ductus arteriosus. Additionally, use of NSAIDs from approximately 20 weeks gestation onward may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment. If treatment with ibuprofen tablets is deemed necessary between 20 and 30 weeks gestation, it is recommended to limit the dosage to the lowest effective amount for the 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 is detected, with follow-up conducted according to clinical practice.

Reproductive studies in rats and rabbits have not indicated developmental abnormalities, although it is important to note that animal reproduction studies may not reliably predict human outcomes. Prostaglandins play a critical role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has been linked to increased 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 given at clinically relevant doses.

There is a lack of information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Consequently, the use of ibuprofen tablets is not recommended for these patients. If therapy with ibuprofen tablets is necessary, close monitoring of renal function is advised.

In animal pharmacology and toxicology studies, the administration of prostaglandin synthesis inhibitors, including ibuprofen, has been associated with increased pre- and post-implantation loss. Additionally, these inhibitors have been shown to impair kidney development when administered at doses relevant to clinical use.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of ibuprofen tablets. Anemia has been reported in patients receiving NSAIDs, including ibuprofen, potentially due to fluid retention, gastrointestinal blood loss, or effects on erythropoiesis. Patients undergoing long-term treatment with ibuprofen should have their hemoglobin or hematocrit monitored if they exhibit signs or symptoms of anemia.

In two postmarketing clinical studies, a higher incidence of decreased hemoglobin levels was observed than previously reported. Specifically, a decrease of 1 gram or more in hemoglobin was noted in 17.1% of 193 patients taking 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients taking 2400 mg daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were documented in these studies.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients using NSAIDs, including ibuprofen tablets. Some cases have resulted in fatal or life-threatening outcomes. DRESS typically presents with symptoms such as fever, rash, lymphadenopathy, and/or facial swelling, and may also involve hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Eosinophilia is frequently observed. Early signs of hypersensitivity, such as fever or lymphadenopathy, may occur even in the absence of a rash. Immediate discontinuation of ibuprofen and patient evaluation is recommended upon the appearance of such symptoms.

Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been associated with NSAID use, including ibuprofen tablets. These serious adverse events can occur without warning. Patients should be educated on the signs and symptoms of serious skin reactions, and ibuprofen should be discontinued at the first indication of a skin rash or any other sign of hypersensitivity.

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. It is important for 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 of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should be encouraged to seek medical advice if they observe any indicative signs or symptoms.

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. Additionally, patients should be alert for symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and should 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 informed of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. In such cases, patients should be instructed to seek immediate emergency help.

Pregnant women should be advised to avoid the use of ibuprofen tablets and other NSAIDs starting at 30 weeks gestation due to the risk of premature closure of the fetal ductus arteriosus. 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 a tight, light-resistant container as defined by the United States Pharmacopeia (USP). It should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F). Care should be taken to avoid exposure to excessive heat, specifically temperatures exceeding 40°C (104°F).

Additional Clinical Information

Physicians should monitor patients on long-term NSAID treatment for signs or symptoms of gastrointestinal bleeding and periodically check complete blood count (CBC) and chemistry profiles. If patients exhibit clinical signs consistent with liver or renal disease, systemic manifestations such as eosinophilia or rash, or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued.

Patients should be counseled to remain vigilant for symptoms of cardiovascular thrombotic events, including chest pain and shortness of breath, and to report these to their healthcare provider immediately. They should also be aware of signs of ulcerations and bleeding, such as epigastric pain and melena, and seek medical advice if these occur. Immediate discontinuation of ibuprofen is advised if any rash or fever develops, and patients should contact their healthcare provider. Additionally, they should be informed about the symptoms of congestive heart failure, hepatotoxicity, and anaphylactoid reactions, and instructed to seek immediate medical attention if these symptoms arise. Pregnant women should avoid ibuprofen and other NSAIDs starting at 30 weeks gestation due to the risk of premature closure of the fetal ductus arteriosus, and those requiring treatment between 20 to 30 weeks should be monitored for oligohydramnios if treatment exceeds 48 hours.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Ibuprofen as submitted by Amneal Pharmaceuticals of New York LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)