Ibuprofen

Description

Ibuprofen tablets 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 exhibits very slight solubility in water (less than 1 mg/mL) but is readily soluble in organic solvents such as ethanol and acetone. The structural formula of ibuprofen is provided below.

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 inactive ingredients such as colloidal silicon dioxide, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, talc, magnesium stearate, and Opadry II, which consists of hypromellose, polyethylene glycol, sodium citrate, lactose monohydrate, and titanium dioxide.

Uses and Indications

Ibuprofen tablets are indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Limitations of Use: Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have not been conducted. Therefore, the use of ibuprofen in pediatric populations should be approached with caution.

Dosage and Administration

Healthcare professionals should carefully consider the potential benefits and risks of ibuprofen tablets and other treatment options before initiating therapy. It is recommended to use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

After assessing the response to initial therapy with ibuprofen tablets, 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, ibuprofen tablets should be administered 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 tailored to each patient, with adjustments made based on the severity of symptoms at the initiation of therapy or in response to treatment outcomes.

It is noted that patients with rheumatoid arthritis may require higher doses of ibuprofen tablets compared to those with osteoarthritis. The smallest effective dose that provides acceptable control should always be employed.

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

Contraindications

Ibuprofen tablets are contraindicated for the treatment of perioperative pain in patients undergoing coronary artery bypass graft (CABG) surgery. Additionally, the use of ibuprofen is not recommended in patients with the aspirin triad, which is characterized by asthma, rhinitis (with or without nasal polyps), and a history of severe bronchospasm following the administration of aspirin or other NSAIDs.

In late pregnancy, ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus. Furthermore, patients with a history of gastrointestinal bleeding or ulcer disease should not take ibuprofen, as they are at a significantly increased risk (greater than 10-fold) for developing gastrointestinal bleeding. Caution is also advised for patients with preexisting asthma, particularly those with aspirin-sensitive asthma, when considering the use of ibuprofen tablets.

Warnings and Precautions

Cardiovascular thrombotic events, including myocardial infarction and stroke, may occur with the use of NSAIDs, potentially leading to fatal outcomes. Patients with a history of cardiovascular disease or those presenting risk factors are at an increased risk. It is recommended to administer the lowest effective dose for the shortest duration necessary to mitigate these risks.

The concurrent use of aspirin does not reduce the risk of serious cardiovascular thrombotic events and may elevate the risk of serious gastrointestinal complications. NSAIDs can also induce new hypertension or exacerbate pre-existing hypertension; therefore, it is essential to monitor blood pressure closely in patients receiving these medications.

Fluid retention and edema have been reported with NSAID use, necessitating caution in patients with heart failure or those prone to fluid retention. Serious gastrointestinal adverse events, such as inflammation, bleeding, ulceration, and perforation, can occur unexpectedly, with or without prior warning symptoms. Patients with a history of ulcer disease or gastrointestinal bleeding are at more than a tenfold increased risk for developing gastrointestinal bleeding.

Long-term use of NSAIDs may lead to renal injury, particularly in patients with pre-existing renal impairment, heart failure, liver dysfunction, and among the elderly. There is insufficient information regarding the safety of ibuprofen in patients with advanced renal disease; therefore, its use is not recommended in this population.

Anaphylactoid reactions may occur; immediate emergency medical assistance should be sought if such a reaction is suspected. Serious skin adverse events, including Stevens-Johnson Syndrome and toxic epidermal necrolysis, can arise without warning. Patients should discontinue use at the first sign of a skin rash or any indication of hypersensitivity.

Due to the risk of premature closure of the ductus arteriosus, NSAIDs should be avoided in late pregnancy.

Healthcare professionals should monitor patients on long-term NSAID therapy for signs and symptoms of gastrointestinal bleeding. Regular laboratory assessments, including complete blood count (CBC) and chemistry profile, are advised for patients undergoing prolonged treatment with NSAIDs. If any signs of liver or renal disease develop, or if abnormal liver tests persist or worsen, ibuprofen should be discontinued.

In cases of an anaphylactoid reaction, emergency medical help must be sought immediately. Patients should be instructed to stop taking the medication and contact their healthcare provider at the first appearance of a skin rash or any other sign of hypersensitivity.

Side Effects

Patients receiving ibuprofen tablets may experience a range of adverse reactions, which can be serious or common.

Serious adverse reactions include an increased risk of cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk is particularly heightened in patients with existing cardiovascular disease or risk factors. Additionally, ibuprofen is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal adverse events are also a significant concern, as NSAIDs, including ibuprofen, can lead to serious complications such as bleeding, ulceration, and perforation of the stomach or intestines, which may occur without warning and can be fatal. Elderly patients are at an increased risk for these gastrointestinal events.

Other serious warnings include the potential for new onset or worsening of hypertension, fluid retention, and edema. Long-term use of NSAIDs has been associated with renal toxicity, including renal papillary necrosis. Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen, and the medication should not be administered to individuals with the aspirin triad. Serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have also been reported and can be fatal.

In clinical trials and postmarketing experiences, additional adverse reactions have been noted. Borderline elevations in liver tests may occur in up to 15% of patients, with rare cases of severe hepatic reactions, including jaundice and hepatic failure, reported. Hematological effects such as anemia and prolonged bleeding time due to inhibited platelet aggregation have been observed. Ophthalmological effects, including blurred vision and changes in color vision, have also been documented. Lastly, aseptic meningitis with fever and coma has been reported in rare instances among patients undergoing ibuprofen therapy.

Patients should be monitored for these adverse reactions, and appropriate measures should be taken to mitigate risks, particularly in those with pre-existing conditions.

Drug Interactions

Concomitant use of certain medications with ibuprofen 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.

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

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

Pharmacokinetic Interactions

• Aspirin: Co-administration of ibuprofen with aspirin may reduce the protein binding of aspirin, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction remains unclear, but the concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

• Lithium: Ibuprofen has been shown to elevate plasma lithium levels and decrease renal clearance of lithium. In a study, the mean minimum lithium concentration increased by 15%, and renal clearance decreased by 19% during concurrent administration. Patients receiving both ibuprofen and lithium should be monitored closely for signs of lithium toxicity.

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

H-2 Antagonists: Studies indicate that the co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine does not significantly affect ibuprofen serum concentrations, suggesting that no dosage adjustments are necessary in this context.

In summary, careful consideration and monitoring are advised 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 is advised when considering the use of ibuprofen in this population. Healthcare professionals should evaluate the potential risks and benefits before prescribing ibuprofen to children.

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

Pregnant patients should be aware that Motrin is classified as Pregnancy Category C. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities; however, it is important to note that animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women to establish safety and efficacy.

Motrin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Additionally, due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, particularly the closure of the ductus arteriosus, the use of Motrin during late pregnancy should be avoided. Healthcare professionals are advised to weigh the risks and benefits when considering the use of this medication in pregnant patients.

Lactation

It is not known whether this drug is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants from ibuprofen tablets, lactating mothers should consider the importance of the drug to their health when making a decision to either discontinue breastfeeding or discontinue the drug.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. 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 discontinued, recovery to the pretreatment state is typically observed.

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.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the prescribing information.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the 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. Initial management included the administration of oxygen and parenteral fluids. Gastric aspiration yielded a greenish-yellow fluid, with no ibuprofen detected. Two hours after ingestion, the child's condition stabilized, although she continued to exhibit periods of 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 responsive, able to sit independently and follow verbal commands. A blood level of ibuprofen measured 102.9 mcg/mL approximately 8½ hours after ingestion, and the child appeared fully recovered by 12 hours.

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 had a blood level of 700 mcg/mL 90 minutes after ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

Management Strategies For acute ibuprofen overdosage, it is recommended to empty the stomach through vomiting or gastric lavage, although recovery of the drug may be minimal 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 are crucial, and the use of oral activated charcoal can be considered to reduce both absorption and reabsorption of ibuprofen.

Severe Cases 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 was placed on bed rest for three days, ultimately recovering without any reported sequelae.

Healthcare professionals should remain vigilant for potential symptoms of ibuprofen overdosage and implement appropriate management strategies to ensure patient safety and recovery.

Nonclinical Toxicology

Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, it is important to note that animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Therefore, Motrin should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, particularly the closure of the ductus arteriosus, use during late pregnancy should be avoided.

In studies involving rats, the administration of NSAIDs has been associated with 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.

No specific details regarding animal pharmacology and toxicology beyond the reproductive studies have been provided.

Postmarketing Experience

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

Anemia has been associated with the use of NSAIDs, including ibuprofen tablets, potentially due to factors such as fluid retention, occult or gross gastrointestinal blood loss, or an incompletely described effect on erythropoiesis. It is recommended that patients on long-term NSAID treatment, including ibuprofen tablets, have their hemoglobin or hematocrit levels monitored if they exhibit any signs or symptoms of anemia.

Reports indicate that NSAIDs may reduce the antihypertensive effect of ACE inhibitors, warranting consideration in patients taking both medications concurrently. Furthermore, while several short-term controlled studies did not demonstrate a significant effect of ibuprofen tablets on prothrombin times or various clotting factors in individuals on coumarin-type anticoagulants, caution is advised. Bleeding events have been reported in patients receiving ibuprofen tablets alongside anticoagulants, and the combined use of warfarin and NSAIDs has been associated with an increased risk of serious gastrointestinal bleeding compared to the use of either drug alone.

Patient Counseling

Patients should be informed of essential information before initiating therapy with ibuprofen tablets, as well as periodically during the course of ongoing therapy. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be made aware that ibuprofen, like other NSAIDs, may cause serious cardiovascular (CV) side effects, including myocardial infarction (MI) or stroke, which could lead to hospitalization or even death. Although serious CV events can occur without warning symptoms, patients should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to seek medical advice if they observe any of these indicative signs or symptoms and understand the importance of follow-up regarding cardiovascular health.

Additionally, patients should be informed that ibuprofen can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may also result in hospitalization or death. Serious GI tract ulcerations and bleeding can occur without warning symptoms; therefore, patients should be vigilant for signs such as epigastric pain, dyspepsia, melena, or hematemesis. They should be instructed to seek medical advice if they experience any of these symptoms and be made aware of the importance of monitoring for gastrointestinal effects.

Patients should also be cautioned that ibuprofen can lead to serious skin side effects, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Although serious skin reactions may occur without warning, patients should be alert for signs such as skin rash, blisters, fever, or other hypersensitivity symptoms like itching. They should be advised to discontinue the medication immediately if any rash develops and to contact their physician as soon as possible.

It is important for patients to promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider. They should also be informed about the warning signs and symptoms of hepatotoxicity, which 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 be educated on the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat. In such cases, they should be instructed to seek immediate emergency help.

Finally, patients should be advised that ibuprofen tablets should be avoided in late pregnancy, as with other NSAIDs, due to the risk of premature closure of the ductus arteriosus.

Storage and Handling

The product is supplied in accordance with the following specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Physicians are advised to monitor patients for signs or symptoms of gastrointestinal (GI) bleeding during treatment. For patients undergoing long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that complete blood counts (CBC) and chemistry profiles be checked periodically to assess for potential adverse effects.

In cases where patients exhibit clinical signs and symptoms indicative of liver or renal disease, or if systemic manifestations such as eosinophilia or rash occur, ibuprofen tablets should be discontinued. Additionally, if abnormal liver tests persist or worsen, immediate cessation of the medication is warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)