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 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.

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 evaluate the potential benefits and risks associated with ibuprofen tablets prior to prescribing, opting for the lowest effective dose for the shortest duration that aligns with individual patient treatment goals.

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

For the management of rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease, the recommended 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, 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 adequate symptom control should always be utilized.

For 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, treatment should commence at the earliest onset of pain, with ibuprofen tablets given at a dose of 400 mg every 4 hours as necessary for effective pain management.

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 includes asthmatic individuals who experience rhinitis with or without nasal polyps, or who have a history of severe bronchospasm following the administration of aspirin or other nonsteroidal anti-inflammatory drugs (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 severe allergic reactions to ibuprofen or other NSAIDs should not take 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 elevated risk. It is recommended that the lowest effective dose of NSAIDs be utilized for the shortest duration necessary to mitigate these risks.

The concurrent use of aspirin does not reduce the heightened risk of serious cardiovascular thrombotic events associated with NSAID use and may increase the likelihood of serious gastrointestinal complications. Additionally, NSAIDs have been associated with the development of new hypertension or exacerbation of pre-existing hypertension; therefore, blood pressure should be monitored closely throughout the duration of NSAID treatment.

Fluid retention and edema have been reported in some patients taking NSAIDs, necessitating caution in individuals with a history of fluid retention or heart failure. Serious gastrointestinal adverse events, such as inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, 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 when using NSAIDs.

Long-term NSAID administration may lead to renal injury, particularly in patients with pre-existing renal impairment, heart failure, liver dysfunction, those on diuretics or ACE inhibitors, and the elderly. Anaphylactoid reactions can occur in patients without prior exposure to ibuprofen, and immediate medical assistance should be sought in such cases. Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis, may arise without warning. NSAID use should be discontinued at the first sign of a skin rash or any indication of hypersensitivity.

Ibuprofen is contraindicated in late pregnancy due to the risk of premature closure of the ductus arteriosus. Both patients and healthcare providers should remain vigilant for signs and symptoms indicative of gastrointestinal ulcerations and bleeding during NSAID therapy, initiating prompt evaluation and treatment if a serious gastrointestinal event is suspected.

For patients undergoing long-term NSAID treatment, periodic monitoring of complete blood count (CBC) and chemistry profiles is advised. Should clinical signs of liver or renal disease manifest, or if abnormal liver tests persist or worsen, ibuprofen should be discontinued. Emergency medical assistance is warranted in cases of anaphylactoid reactions, and NSAID use should be halted immediately upon the appearance of a skin rash or any other signs of hypersensitivity.

Side Effects

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

Serious Adverse Reactions

Boxed warnings highlight significant risks associated with ibuprofen use. There is an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, particularly with prolonged use. This risk is heightened in patients with existing cardiovascular disease or risk factors. Additionally, ibuprofen is contraindicated for the treatment of perioperative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Gastrointestinal risks are also notable, as NSAIDs, including ibuprofen, can lead to serious gastrointestinal adverse events such as bleeding, ulceration, and perforation of the stomach or intestines, which may occur without warning and can be fatal. Elderly patients are particularly vulnerable to these serious gastrointestinal complications.

Other serious adverse reactions include renal effects, where long-term use of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. Anaphylactoid reactions may occur even in patients without prior exposure to ibuprofen, and the medication should not be administered to individuals with the aspirin triad. Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have also been reported and can be fatal.

Common Adverse Reactions

In addition to serious reactions, patients may experience common adverse effects. These include hypertension, which can manifest as new onset or worsening of pre-existing hypertension. Fluid retention and edema have been observed in some patients taking NSAIDs.

Hematological effects such as anemia may occur, as NSAIDs can inhibit platelet aggregation and prolong bleeding time. Hepatic effects are also noted, with borderline elevations in liver tests occurring in up to 15% of patients. Rare but severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, have been reported.

Ophthalmological effects, including blurred or diminished vision, scotomata, and changes in color vision, have been documented. Additionally, aseptic meningitis, characterized by fever and coma, has been observed 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 or risk factors.

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 already receiving ACE-inhibitors.

• Diuretics: Ibuprofen has been shown to diminish the natriuretic effect of diuretics such as furosemide and thiazides in some patients, likely due to the inhibition of renal prostaglandin synthesis. Close monitoring for signs of renal failure and assessment of diuretic efficacy is recommended during concomitant therapy.

• Warfarin-Type Anticoagulants: While short-term studies have not demonstrated a significant effect 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 risk of serious gastrointestinal bleeding. 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 associated with elevated plasma lithium levels and decreased 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 no clinically relevant interaction.

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 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 (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 carefully consider the risks and benefits when prescribing this medication to 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 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 at greatest risk for these adverse effects include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. 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 for these patients. 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

Approximately 1½ hours following the ingestion of 7 to 10 ibuprofen tablets (400 mg) by a 19-month-old child weighing 12 kg, the child presented to the hospital emergency room in a state of apnea and cyanosis, responding only to painful stimuli. This stimulus was sufficient to induce respiration. Upon admission, the child received oxygen and parenteral fluids, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen. Two hours post-ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced apnea lasting 5 to 10 seconds. The child was subsequently admitted to intensive care, where sodium bicarbonate, along with infusions of dextrose and normal saline, was administered. By four hours after ingestion, the child could be easily aroused, sit independently, and respond to verbal commands. A blood level of ibuprofen measured 102.9 mcg/mL approximately 8½ hours post-ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional cases involving children, each weighing approximately 10 kg, accidental acute ingestion of approximately 120 mg/kg of ibuprofen resulted in no signs of acute intoxication or late sequelae. Notably, one child's blood level was recorded at 700 mcg/mL 90 minutes after ingestion, which is about ten times the peak levels observed in absorption-excretion studies.

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

In instances of acute overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage; however, it should be noted that minimal drug recovery is expected 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 theoretically beneficial. Additionally, supportive measures should be complemented with the use of oral activated charcoal, which may aid in reducing both the absorption and reabsorption of ibuprofen tablets.

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 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

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.

It is recognized that nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, inhibit platelet aggregation and may prolong bleeding time in some patients. Therefore, patients receiving ibuprofen tablets who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or those on anticoagulant therapy, should be monitored closely.

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.

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 encouraged to seek medical advice if they experience any of these symptoms and to recognize the importance of follow-up.

Patients should also be made aware of the potential for serious skin side effects associated with ibuprofen, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may lead to 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 instructed to stop 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 physicians. They should also be informed about the warning signs and symptoms of hepatotoxicity, which may include nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms. If these occur, patients should be instructed to discontinue 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, and should be advised to seek immediate emergency help if these symptoms arise.

Finally, patients should be informed 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 National Drug Code (NDC) 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

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as there is a risk of serious GI tract ulcerations and bleeding associated with the use of ibuprofen. For patients undergoing long-term treatment 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, such as eosinophilia or rash, or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued promptly to mitigate further risk.

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)