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 its very slight solubility in water (less than 1 mg/mL) and its ready solubility in organic solvents such as ethanol and acetone. The structural formula of ibuprofen is represented 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, including flare-ups of chronic disease, 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.

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 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 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 prior history of peptic ulcer disease and/or gastrointestinal bleeding are at a significantly increased risk (greater than 10-fold) for developing gastrointestinal bleeding when using NSAIDs. Patients should discontinue ibuprofen immediately if any rash develops and seek medical attention promptly.

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 heightened risk of serious cardiovascular thrombotic events associated with NSAID use and may elevate the risk of serious gastrointestinal complications. Therefore, caution is advised when considering the combination of these medications.

NSAIDs have the potential to induce new hypertension or exacerbate existing hypertension. Regular monitoring of blood pressure is essential during treatment. Additionally, fluid retention and edema have been reported; thus, NSAIDs should be used cautiously in patients with a history of fluid retention or heart failure.

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 particularly vulnerable and should be monitored closely for signs and symptoms of gastrointestinal bleeding throughout NSAID therapy. If a serious gastrointestinal event is suspected, discontinuation of the NSAID is warranted.

Long-term use of NSAIDs may lead to renal injury, especially in patients with pre-existing renal impairment, heart failure, liver dysfunction, and among the elderly. Regular monitoring of renal function is advised, and patients on long-term NSAID treatment should have their complete blood count (CBC) and chemistry profile evaluated periodically. Discontinuation of the NSAID should occur if clinical signs of liver or renal disease develop or if abnormal liver tests persist or worsen.

Anaphylactoid reactions may occur; in such cases, emergency medical assistance should be sought immediately. Serious skin adverse events, including exfoliative dermatitis, 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 and contact their healthcare provider.

Use of NSAIDs in late pregnancy is contraindicated due to the risk of premature closure of the ductus arteriosus.

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 warnings include the potential for fluid retention and edema, which have been observed in some patients. Long-term use of NSAIDs has been associated with renal toxicity, including renal papillary necrosis and other forms of renal injury, especially in patients who rely on renal prostaglandins for maintaining renal perfusion. 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, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can also occur without warning and may be fatal.

Common Adverse Reactions

In clinical trials and postmarketing experiences, additional adverse reactions have been reported. Borderline elevations in liver tests may occur in up to 15% of patients taking NSAIDs, including ibuprofen, with rare cases of severe hepatic reactions such as jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some of which have resulted in death. Anemia has been noted in some patients, as NSAIDs can inhibit platelet aggregation and prolong bleeding time.

Ophthalmological effects, including blurred or diminished vision, scotomata, and changes in color vision, have also been reported. Rare instances of aseptic meningitis, characterized by fever and coma, have been observed in patients undergoing ibuprofen therapy.

Healthcare providers should monitor patients for these adverse reactions and weigh the benefits and risks of ibuprofen therapy, 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 who are concurrently taking 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 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 ibuprofen, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction is unclear, but it is generally not recommended to use ibuprofen and aspirin together due to the potential for increased adverse effects.

• Lithium: Ibuprofen can elevate plasma lithium levels and decrease renal clearance of lithium, with observed increases in mean minimum lithium concentration and reductions in renal clearance during concurrent administration. Patients should be monitored closely for signs of lithium toxicity when these drugs are used together.

• 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 essential when ibuprofen is prescribed alongside 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 in pediatric patients have not been established. Therefore, healthcare professionals should exercise caution 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 this medication 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. Healthcare professionals should exercise caution, particularly during late pregnancy, due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, specifically the risk of closure of the ductus arteriosus. Therefore, use of this medication in the later stages of pregnancy should be avoided.

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 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

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the age and weight of the patient.

Clinical Presentation

A notable case involved a 19-month-old child weighing 12 kg, 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 the severity of the symptoms, this stimulus was sufficient to induce respiration. Upon examination, a greenish-yellow fluid was aspirated from the stomach, with no evidence of ibuprofen detected. Two hours after ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced 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 alert, able to sit independently, and responsive to verbal commands. A blood level of ibuprofen measured 102.9 mcg/mL approximately 8½ hours after ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional cases involving children weighing approximately 10 kg who ingested about 120 mg/kg of ibuprofen, no signs of 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, the patient received parenteral hydration and was placed on bed rest for three days, after which he recovered without any reported sequelae.

Management Recommendations

In instances of acute ibuprofen overdosage, it is recommended to empty the stomach 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 beneficial. Supportive measures should be implemented, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant in monitoring patients for potential complications and provide appropriate supportive care as needed.

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, as with 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.

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 undergoing 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. Several short-term controlled studies have not demonstrated a significant effect of ibuprofen tablets on prothrombin times or various clotting factors in individuals on coumarin-type anticoagulants. However, due to reports of bleeding associated with the use of ibuprofen tablets and other NSAIDs in patients on anticoagulants, caution is advised when prescribing ibuprofen tablets in this population.

Aseptic meningitis, accompanied by fever and coma, has been observed infrequently in patients receiving ibuprofen therapy. While this condition is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has also been reported in individuals without underlying chronic conditions. If signs or symptoms of meningitis arise in a patient taking ibuprofen tablets, the potential association with the medication should be evaluated.

Patient Counseling

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

Healthcare providers should discuss the potential for serious cardiovascular (CV) side effects associated with ibuprofen tablets, including myocardial infarction (MI) and stroke, which may lead to hospitalization or death. Patients should be made aware that serious CV events can occur without warning symptoms. They should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, and slurring of speech, and should seek medical advice if they observe any of these indicative signs or symptoms. The importance of follow-up in this regard should be emphasized.

Additionally, patients should be informed that ibuprofen tablets 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. Patients should be vigilant for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they experience any of these symptoms. The significance of follow-up should be clearly communicated.

Patients should also be made aware of the risk of serious skin side effects associated with ibuprofen tablets, such as 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 and symptoms such as skin rash, blisters, fever, or other signs of hypersensitivity like itching. They should be advised to discontinue the medication immediately if any type of 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, including 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 and swelling of the face or throat. In the event of these symptoms, they should be instructed to seek immediate emergency help.

Finally, healthcare providers should advise patients 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 various package configurations, with specific NDC numbers available for identification. 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

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as serious ulcerations and bleeding may occur without warning. 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, or if systemic manifestations such as eosinophilia or rash develop, it is crucial to discontinue ibuprofen tablets. Additionally, if abnormal liver tests persist or worsen, immediate cessation of the medication is advised.

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)