Ibuprofen

Description

Ibuprofen tablets, USP contain the active ingredient ibuprofen, which is chemically defined as (±) - 2 - (p - isobutylphenyl) propionic acid. Ibuprofen appears as a white powder with a melting point of 74-77°C. It is characterized by 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 300 mg, 400 mg, 600 mg, and 800 mg. The tablets contain several inactive ingredients, including colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polyethylene glycol, sodium starch glycolate, 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

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. This can be administered as 300 mg, 400 mg, 600 mg, or 800 mg taken three to four times daily (tid or qid). The total daily dose should not exceed 3200 mg. Dosing should be tailored to each patient, with adjustments made based on the severity of symptoms.

For the management of mild to moderate pain, a dose of 400 mg may be taken every 4 to 6 hours as needed for pain relief. In cases of dysmenorrhea, ibuprofen tablets should be administered at a dose of 400 mg every 4 hours as necessary for pain relief.

To minimize gastrointestinal complaints, it is recommended that ibuprofen tablets be taken with meals or milk.

After evaluating the patient's response to initial therapy, healthcare professionals should adjust the dose and frequency to meet individual patient needs. A therapeutic response may be observed within a few days to a week, but is most commonly noted by two weeks. Once a satisfactory response is achieved, the patient's dosage should be reviewed and modified as necessary.

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

Cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, have been associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and these events may be fatal. The risk of such events may increase with the duration of NSAID use. It is important to note that ibuprofen is contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs are also linked to serious gastrointestinal (GI) adverse events, which can include bleeding, ulceration, and perforation of the stomach or intestines, potentially leading to fatal outcomes. These serious GI events can occur at any time during treatment and may arise without warning symptoms. Elderly patients are particularly at increased risk for these gastrointestinal complications.

To mitigate potential risks, it is recommended to use the lowest effective dose of NSAIDs for the shortest duration necessary. Blood pressure should be monitored closely during NSAID treatment, especially in patients with a history of hypertension. Additionally, NSAIDs should be prescribed with caution to patients who have a history of ulcer disease or gastrointestinal bleeding. In cases where NSAID treatment is deemed necessary for patients with advanced renal disease, renal function should be monitored closely.

In the event of an anaphylactoid reaction, which may occur in patients without prior exposure to ibuprofen, immediate emergency medical assistance should be sought.

Patients should discontinue ibuprofen at the first sign of a skin rash or any other indication of hypersensitivity. If symptoms suggestive of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) occur, ibuprofen should be stopped, and the patient should be evaluated immediately.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication, which can be 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 increase 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 and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Gastrointestinal reactions are among the most commonly reported and include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. More severe gastrointestinal issues 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 effects may include dizziness, headache, nervousness, depression, insomnia, confusion, emotional liability, and somnolence. In rare cases, aseptic meningitis with fever and coma has been reported.

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

Adverse reactions affecting the special senses include tinnitus, hearing loss, amblyopia, conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic reactions may involve neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia (with or without purpura), eosinophilia, and decreases in hemoglobin and hematocrit, as well as bleeding episodes such as epistaxis and menorrhagia.

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

Cardiovascular reactions may present as 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 (including sinus tachycardia and sinus bradycardia).

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

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

Healthcare providers should monitor patients closely for these adverse reactions and consider the risk factors associated with their occurrence.

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 significant with enteric-coated low-dose aspirin. To mitigate this risk, it is advisable to administer immediate-release low-dose aspirin at least 2 hours prior to ibuprofen. For patients taking low-dose aspirin for cardioprotection who require analgesics, alternative NSAIDs that do not affect aspirin's antiplatelet effect or non-NSAID analgesics should be considered.

• Diuretics: Ibuprofen may diminish the natriuretic effect of diuretics such as furosemide and thiazides, likely due to inhibition of renal prostaglandin synthesis. Patients should be monitored closely for signs of renal failure and to ensure diuretic efficacy during concomitant therapy.

• Lithium: The use of ibuprofen can elevate plasma lithium levels and decrease renal clearance of lithium, potentially leading to lithium toxicity. Careful monitoring for signs of 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 shown significant effects of ibuprofen on prothrombin times in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of warfarin and NSAIDs can lead to a higher 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 does not appear to significantly affect ibuprofen serum concentrations, indicating no major pharmacokinetic interaction.

In summary, careful consideration and monitoring are essential when ibuprofen is used in conjunction with these medications to mitigate potential adverse effects and ensure therapeutic efficacy.

Packaging & NDC

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

Pediatric Use

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

Geriatric Use

Caution should be exercised when treating elderly patients, specifically those aged 65 years and older, with nonsteroidal anti-inflammatory drugs (NSAIDs). Due to the increased likelihood of adverse reactions in this population, careful monitoring and consideration of individual patient factors are essential. It is important for healthcare providers to assess the risks versus benefits of NSAID therapy in geriatric patients, as they may have a higher susceptibility to side effects and complications.

Pregnancy

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy is associated with potential risks to the fetus. Specifically, NSAID use 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. Due to these risks, 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 NSAID use at about 30 weeks gestation or later significantly 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 associated with fetal renal dysfunction leading to oligohydramnios, with some cases resulting in neonatal renal impairment. These adverse outcomes typically occur after days to weeks of treatment, although oligohydramnios has been reported as soon as 48 hours after NSAID initiation. In many instances, the decrease in amniotic fluid was transient and reversible upon cessation of the drug; however, there have been limited case reports of irreversible neonatal renal dysfunction requiring invasive procedures.

Reproductive studies in rats and rabbits have not demonstrated developmental abnormalities; however, animal reproduction studies are not always predictive of human response. Prostaglandins play a crucial role in endometrial vascular permeability, blastocyst implantation, and decidualization, and their synthesis inhibitors, such as ibuprofen, have been shown to impair kidney development in animal studies when administered at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population(s) 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 the use of ibuprofen tablets 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 of oligohydramnios, 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 unknown. Furthermore, it is not established whether ibuprofen is excreted in human milk. Given the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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. Renal toxicity may occur in patients where renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs can lead to a dose-dependent reduction in prostaglandin formation, which may subsequently decrease renal blood flow and precipitate overt renal decompensation.

Patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly are at the greatest risk for these adverse reactions. In cases where NSAID therapy is initiated, close monitoring of renal function is advisable. 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. 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 instances, neonatal renal impairment. Oligohydramnios may be reversible upon discontinuation of treatment; however, ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up conducted 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 use 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 heightened 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 the initiation of ibuprofen tablet therapy 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 and Symptoms A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg). Approximately 1½ hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli. Despite this, the stimulus was sufficient to induce respiration. Initial management included the administration of oxygen and parenteral fluids, along with gastric aspiration, which revealed a greenish-yellow fluid without evidence of ibuprofen. Two hours after ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced intermittent apnea lasting 5 to 10 seconds. The child was subsequently admitted to intensive care, where sodium bicarbonate, dextrose, and normal saline infusions were administered. By four hours post-ingestion, the child was more responsive, able to sit independently, and followed spoken commands. Blood levels 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 of ibuprofen, no acute intoxication or late 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.

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

Management of Overdosage In instances of acute ibuprofen overdosage, it is recommended that the stomach be emptied 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 alkali and inducing diuresis may be beneficial. Supportive measures should be prioritized, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant for potential symptoms and manage cases of overdosage with appropriate interventions to ensure patient safety and recovery.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy has been associated with teratogenic effects, particularly when administered around 20 weeks gestation or later. Notably, these medications may increase the risk of premature closure of the fetal ductus arteriosus and can lead to fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment. While oligohydramnios may be reversible upon discontinuation of treatment, prolonged cases can lead to complications such as limb contractures and delayed lung maturation.

In contrast, reproductive studies conducted in rats and rabbits have not indicated developmental abnormalities, although it is important to note that animal reproduction studies do not always predict human outcomes. Prostaglandins play a critical role in various reproductive processes, including 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, these inhibitors have been shown to impair fetal kidney development when given at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage in the indicated population remains unknown. 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.

Data from observational studies regarding potential embryofetal risks associated with NSAID use during the first or second trimesters of pregnancy are inconclusive. 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. The effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown.

Postmarketing Experience

During postapproval use of ibuprofen, several adverse reactions have been identified. These include exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

It is important to note that 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.

Patient Counseling

Patients should be informed of essential information before initiating therapy with an NSAID, such as Ibuprofen tablets, and periodically during the course of ongoing therapy. They should be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

Healthcare providers should advise patients to be alert 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.

Patients should be made aware that Ibuprofen tablets, like other NSAIDs, can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be vigilant for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis. They should be apprised of the importance of seeking medical advice upon observing any indicative signs or symptoms.

Patients should be advised to stop taking Ibuprofen tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible. Additionally, they should be alert for symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms occur.

It is important 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 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. If these symptoms occur, 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.

Healthcare providers should monitor patients for signs or symptoms of GI bleeding, as serious GI tract ulcerations and bleeding can occur without warning symptoms. Patients on long-term treatment with NSAIDs should have their complete blood count (CBC) and chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash), or if abnormal liver tests persist or worsen, Ibuprofen tablets should be discontinued.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a controlled room temperature of 20°C to 25°C (68°F to 77°F), as defined by the United States Pharmacopeia (USP). Care should be taken to avoid exposure to excessive heat, specifically temperatures exceeding 40°C (104°F). Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Physicians should monitor patients for signs or symptoms of gastrointestinal bleeding, particularly in those undergoing long-term treatment with NSAIDs, who should have their complete blood count (CBC) and chemistry profile checked periodically. 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 cessation of ibuprofen is advised if any rash or fever develops, and patients should contact their healthcare provider. Additionally, signs of congestive heart failure, hepatotoxicity, and anaphylactoid reactions should be monitored closely, with instructions 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. Postmarketing experience has identified adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and fixed drug eruption associated with ibuprofen use.

FDA Insert (PDF)

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

View full prescribing information (PDF)