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 ranging from 74 to 77 °C. It is characterized by very slight solubility in water (less than 1 mg/mL) and is readily soluble in organic solvents such as ethanol and acetone. The structural formula of ibuprofen is provided below.

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

Uses and Indications

Ibuprofen Tablets, USP 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.

Limitations of Use: Controlled clinical trials to establish the safety and effectiveness of Ibuprofen Tablets, USP in pediatric populations have not been conducted. Therefore, the use of this medication in children is not recommended until further evidence is available.

Dosage and Administration

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

After evaluating the response to initial therapy with Ibuprofen Tablets, USP, the dose and frequency should be adjusted to meet the specific needs of the patient. The total daily dose should not exceed 3200 mg. In cases where gastrointestinal complaints arise, it is advisable to administer Ibuprofen Tablets, USP with meals or milk to mitigate these effects.

For the management of rheumatoid arthritis and osteoarthritis, the suggested dosage ranges from 1200 mg to 3200 mg daily, typically administered as 400 mg, 600 mg, or 800 mg three to four times a day (tid or qid). The dosage should be individualized, allowing for adjustments based on the severity of symptoms at the initiation of therapy or in response to treatment.

For mild to moderate pain, a dose of 400 mg may be taken every 4 to 6 hours as needed for pain relief. In the case of dysmenorrhea, treatment should commence at the earliest onset of pain, with Ibuprofen Tablets, USP administered at a dose of 400 mg every 4 hours as necessary for effective pain relief.

Contraindications

Ibuprofen Tablets, USP are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, the use of Ibuprofen Tablets, USP 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 documented in these patients. Furthermore, Ibuprofen Tablets, USP are contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen Tablets, USP, are associated with a significant risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, which may be fatal. This risk can manifest early in treatment and is likely to increase with prolonged use. It is important to note that Ibuprofen Tablets, USP are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

In addition to cardiovascular risks, NSAIDs can lead to severe gastrointestinal adverse 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. Elderly patients are particularly vulnerable to these serious gastrointestinal events.

Clinical studies have demonstrated that the risk of serious cardiovascular thrombotic events is consistent across all NSAIDs; however, patients with pre-existing cardiovascular disease or risk factors exhibit a higher absolute incidence of these events. Furthermore, NSAIDs may contribute to the onset of new hypertension or exacerbate existing hypertension. Long-term use of NSAIDs has been linked to renal complications, including renal papillary necrosis and other forms of renal injury.

Anaphylactoid reactions have been reported in patients who have not previously been exposed to Ibuprofen Tablets, USP. In the event of such a reaction, immediate emergency medical assistance should be sought. Additionally, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been observed in patients taking NSAIDs like Ibuprofen Tablets, USP. If any signs or symptoms indicative of DRESS occur, the medication should be discontinued, and the patient should be evaluated without delay.

Ibuprofen Tablets, USP are not intended to replace corticosteroids or to address corticosteroid insufficiency. Abrupt cessation of corticosteroids can lead to exacerbation of the underlying condition. For patients on long-term corticosteroid therapy, a gradual tapering of the corticosteroid dosage is recommended if discontinuation is necessary.

The pharmacological effects of Ibuprofen Tablets, USP in reducing fever and inflammation may obscure diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions.

Healthcare professionals should monitor patients for signs or symptoms of gastrointestinal bleeding, particularly in those receiving long-term NSAID therapy. Regular assessments of complete blood count (CBC) and chemistry profiles are advised. If any clinical signs or symptoms indicative of liver or renal disease develop, or if systemic manifestations such as eosinophilia or rash occur, or if abnormal liver tests persist or worsen, Ibuprofen Tablets, USP should be discontinued.

In cases of anaphylactoid reactions, immediate emergency medical help is essential. Additionally, if signs or symptoms of DRESS are present, Ibuprofen Tablets, USP should be discontinued, and the patient should be evaluated promptly.

Side Effects

Patients may experience a range of adverse reactions while using the medication. Common adverse reactions reported in controlled clinical trials include gastrointestinal complaints, with an incidence ranging from 4% to 16%.

Serious adverse reactions are of particular concern. There is an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is likely to increase with prolonged use. Additionally, patients face an elevated risk of serious gastrointestinal adverse events, such as 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. Elderly patients are at a heightened risk for these serious gastrointestinal complications.

Postmarketing experience has revealed further serious skin and appendage reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Warnings associated with the medication include the potential for anaphylactoid reactions, which may occur in patients without prior exposure to ibuprofen. It is contraindicated in patients with the aspirin triad. Serious skin reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), exfoliative dermatitis, SJS, and TEN, can be fatal; therefore, discontinuation of the medication is advised at the first sign of a skin rash or any other indication of hypersensitivity.

Additional adverse reactions of note include renal effects, where long-term administration may lead to renal papillary necrosis and other forms of renal injury. Patients at greatest risk include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Hepatic effects may also occur, with borderline elevations of liver tests reported in up to 15% of patients. Rare but severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some of which have resulted in fatal outcomes, have been documented.

Hematological effects such as anemia may arise due to fluid retention, occult or gross gastrointestinal blood loss, or impacts on erythropoiesis. Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit platelet aggregation and prolong bleeding time. Ophthalmological effects, including blurred and/or diminished vision, scotomata, and changes in color vision, have also been reported. Lastly, aseptic meningitis has been rarely observed in patients undergoing ibuprofen therapy, particularly in those with systemic lupus erythematosus and related connective tissue diseases.

Drug Interactions

Concomitant use of certain medications with Ibuprofen Tablets, USP may lead to significant drug interactions, which can affect therapeutic outcomes and safety. The following interactions have been identified:

Pharmacodynamic Interactions

• ACE-Inhibitors: Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may reduce the antihypertensive effect of ACE-inhibitors. Clinicians should consider this interaction when prescribing NSAIDs to patients who are concurrently taking ACE-inhibitors.

• Aspirin:

  • The antiplatelet activity of aspirin may be compromised when ibuprofen (400 mg three times daily) is administered concurrently with enteric-coated low-dose aspirin. This interaction persists even with a once-daily regimen of ibuprofen, particularly if ibuprofen is taken before aspirin.

  • To mitigate this interaction, immediate-release low-dose aspirin should be administered at least 2 hours prior to ibuprofen. However, this timing does not apply to enteric-coated formulations.

  • Due to the potential increased risk of cardiovascular events from this interaction, it is advisable to consider alternative analgesics that do not interfere with aspirin's antiplatelet effect for patients using low-dose aspirin for cardioprotection.

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

• Warfarin-type Anticoagulants: While short-term studies have not shown significant effects of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, there is a documented risk of increased bleeding. The combination of ibuprofen and anticoagulants may lead to a higher incidence of serious gastrointestinal bleeding compared to either drug alone. Caution is advised when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

• Lithium: Ibuprofen has been shown to elevate plasma lithium levels and decrease renal clearance of lithium, with a mean increase in minimum lithium concentration of 15% and a 19% reduction in renal clearance. This interaction is attributed to the inhibition of renal prostaglandin synthesis. Patients receiving both ibuprofen and lithium should be closely monitored for signs of lithium toxicity.

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

• H-2 Antagonists: Co-administration of ibuprofen with cimetidine or ranitidine does not appear to significantly affect ibuprofen serum concentrations, indicating no substantial pharmacokinetic interaction.

In summary, careful consideration and monitoring are recommended 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

Safety and effectiveness of Ibuprofen Tablets, USP 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

The use of NSAIDs, including Ibuprofen Tablets, USP, in pregnant patients, particularly after approximately 20 weeks of gestation, is associated with significant risks. Administration of these medications during this period may lead to fetal renal dysfunction, which can result in oligohydramnios and, in some instances, neonatal renal impairment. These adverse outcomes typically manifest after days to weeks of treatment; however, oligohydramnios has been infrequently reported as early as 48 hours following the initiation of NSAID therapy. While oligohydramnios may be reversible upon discontinuation of the medication, prolonged cases can lead to serious complications, including limb contractures and delayed lung maturation. In certain postmarketing reports, affected neonates required invasive interventions such as exchange transfusion or dialysis due to impaired renal function.

Healthcare professionals are advised to avoid the use of Ibuprofen Tablets, USP, in pregnant women at around 30 weeks of gestation and later, as this increases the risk of premature closure of the fetal ductus arteriosus. If NSAID treatment is deemed necessary between 20 and 30 weeks of gestation, it is crucial to limit the use of Ibuprofen Tablets, USP to the lowest effective dose for the shortest duration possible. Additionally, ultrasound monitoring of amniotic fluid levels should be considered if treatment extends beyond 48 hours. Should oligohydramnios occur, Ibuprofen Tablets, USP should be discontinued, and appropriate follow-up should be conducted in accordance with clinical practice guidelines.

Lactation

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

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. In patients 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, USP in patients with advanced renal disease, and treatment in this population is not recommended. If initiation of ibuprofen tablet therapy is deemed necessary, close monitoring of renal function is advised.

Additionally, the use of NSAIDs, including Ibuprofen Tablets, USP, 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. If NSAID treatment is required between approximately 20 and 30 weeks of gestation, it is recommended to limit the use of Ibuprofen Tablets, USP 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, USP 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 Ibuprofen Tablets, USP. Long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with renal complications, including renal papillary necrosis and other forms of renal injury. 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.

Particular caution is warranted for patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly, as they are at an increased risk for renal toxicity. In these populations, close monitoring of renal function is advisable if Ibuprofen Tablets, USP therapy is initiated.

Due to the lack of controlled clinical study data regarding the use of Ibuprofen Tablets, USP in patients with advanced renal disease, treatment with this medication is not recommended for such patients. If therapy is deemed necessary, it should be accompanied by vigilant monitoring of renal function to mitigate potential risks. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of careful management in patients with hepatic impairment.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations and management strategies are critical for effective intervention.

Clinical Presentation A notable case involved a 19-month-old child weighing 12 kg who ingested 7 to 10 ibuprofen tablets (400 mg each). Approximately 30 minutes 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, with a greenish-yellow fluid aspirated from the stomach, showing no evidence of ibuprofen. Two hours after ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced apnea lasting 5 to 10 seconds. Following admission to intensive care, sodium bicarbonate, 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 µg/mL approximately 8.5 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 signs of acute intoxication or late sequelae were observed. One child exhibited a blood level of 700 µg/mL 90 minutes post-ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

A separate case involving a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours reported dizziness, with nystagmus observed during examination. After hospitalization, the patient received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

Management Strategies In instances of acute ibuprofen overdosage, it is recommended to empty the stomach 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 are essential, and the use of oral activated charcoal can aid in reducing both absorption and reabsorption of ibuprofen.

Healthcare professionals should remain vigilant in monitoring patients for potential symptoms and complications associated with ibuprofen overdosage, ensuring appropriate interventions are implemented promptly.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen Tablets, USP, during pregnancy, particularly at approximately 30 weeks gestation or later, has been associated with an increased risk of premature closure of the fetal ductus arteriosus. Additionally, administration of NSAIDs around 20 weeks gestation or later has been linked to fetal renal dysfunction, which may lead to oligohydramnios and, in some instances, neonatal renal impairment. In animal studies, the use of prostaglandin synthesis inhibitors, such as ibuprofen, resulted in increased pre- and post-implantation loss. Prostaglandins are known to play a critical role in fetal kidney development, and published animal studies have indicated that prostaglandin synthesis inhibitors can impair kidney development when administered at clinically relevant doses.

Data from observational studies regarding other potential embryofetal risks associated with NSAID use during the first or second trimesters of pregnancy remain inconclusive. Reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, it is important to note that animal reproduction studies do not always predict human responses.

In studies involving rats, the administration of NSAIDs, similar to other drugs that inhibit prostaglandin synthesis, resulted in an increased incidence of dystocia, delayed parturition, and decreased pup survival.

Postmarketing Experience

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

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

Patient Counseling

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

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

It is important to inform patients that Ibuprofen Tablets, USP, like other NSAIDs, can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects such as ulcers and bleeding, which may lead to hospitalization or even death. Patients should be made aware that serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms. They should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they observe any indicative signs or symptoms.

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

In addition, patients should be informed about 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.

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

For pregnant women, it is crucial to inform them to avoid the use of Ibuprofen Tablets, USP, 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, USP 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 that complies with the standards set forth by the United States Pharmacopeia (USP) and features a child-resistant closure. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. 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 (GI) bleeding, as serious GI tract ulcerations and bleeding can occur without warning. For patients undergoing long-term treatment with NSAIDs, it is recommended that clinicians periodically check complete blood count (CBC) and chemistry profiles. If patients exhibit clinical signs and symptoms indicative of liver or renal disease, or if systemic manifestations such as eosinophilia or rash develop, or if abnormal liver tests persist or worsen, discontinuation of Ibuprofen Tablets, USP is advised.

During postmarketing surveillance, several adverse reactions have been reported, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

FDA Insert (PDF)

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

View full prescribing information (PDF)