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, quantified at less than 1 mg/mL, while being 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 also contain several inactive ingredients, including colloidal silicon dioxide, croscarmellose sodium, hypromellose 2910, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, pregelatinized starch, povidone k-90, sodium lauryl sulfate, 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. This can be achieved through various dosing regimens, such as 300 mg four times a day or 400 mg, 600 mg, or 800 mg three to four times a day. 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 utilized. In chronic conditions, a therapeutic response may be observed within a few days to a week, but is most commonly seen by two weeks. Following a satisfactory response, the patient's dosage should be reviewed and adjusted as necessary.

For the relief of mild to moderate pain, ibuprofen tablets may be administered at a dose of 400 mg every 4 to 6 hours as needed. 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 pain relief.

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. They should not be administered to individuals who have experienced asthma, urticarial, or allergic-type reactions following the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been reported in these patients. Additionally, the use of ibuprofen tablets is contraindicated in the context of coronary artery bypass graft (CABG) surgery.

Caution is advised when considering ibuprofen for patients with preexisting asthma, particularly those with aspirin-sensitive asthma.

Warnings and Precautions

Patients receiving ibuprofen tablets should be aware of several critical warnings and precautions associated with their use.

Cardiovascular Risks Clinical trials have demonstrated that both COX-2 selective and nonselective NSAIDs, including ibuprofen, are associated with an increased risk of serious cardiovascular thrombotic events, such as myocardial infarction (MI) and stroke, which may be fatal. This risk is evident in patients with and without pre-existing cardiovascular (CV) disease or risk factors; however, those with known CV disease or risk factors experience a higher absolute incidence of these events. The risk of CV thrombotic events is particularly pronounced at higher doses. Ibuprofen is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Furthermore, patients treated with NSAIDs in the post-MI period face an elevated risk of reinfarction, CV-related death, and all-cause mortality. Therefore, the use of ibuprofen tablets in patients with a recent MI should be approached with caution, weighing the potential benefits against the risk of recurrent CV thrombotic events.

Gastrointestinal and Renal Risks Ibuprofen tablets can lead to serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, which can be fatal. Long-term use of NSAIDs has also been associated with renal complications, such as renal papillary necrosis and other forms of renal injury. Physicians should monitor patients on long-term NSAID therapy for signs or symptoms of gastrointestinal bleeding and periodically check complete blood count (CBC) and chemistry profiles.

Hypersensitivity Reactions Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen. Patients should seek emergency medical assistance if such reactions occur. Additionally, patients should discontinue ibuprofen tablets at the first sign of a skin rash or any other indication of hypersensitivity. Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported and can be fatal.

Hypertension and Asthma Considerations NSAIDs, including ibuprofen, may lead to the onset of new hypertension or exacerbate pre-existing hypertension. Patients with asthma should be evaluated for aspirin-sensitive asthma, as ibuprofen is contraindicated in these individuals.

Corticosteroid Considerations Ibuprofen tablets are not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. For patients on prolonged corticosteroid therapy, a gradual tapering of corticosteroids is recommended if discontinuation is necessary.

Monitoring Parameters Patients on long-term NSAID treatment should have their hemoglobin or hematocrit levels checked if they exhibit any signs or symptoms of anemia. Additionally, those who may be adversely affected by alterations in platelet function should be closely monitored.

Pregnancy Considerations In late pregnancy, ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus.

In summary, healthcare professionals should ensure that patients are adequately informed of these warnings and precautions, and appropriate monitoring should be implemented to mitigate risks associated with ibuprofen tablet use.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication, categorized by seriousness and frequency.

Serious adverse reactions include an increased risk of cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is known to increase with prolonged use. Additionally, serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, can occur at any time during therapy and may also be fatal. Elderly patients are particularly at heightened risk for these gastrointestinal complications. Renal effects, such as acute renal failure and renal papillary necrosis, have been observed with long-term administration.

Common adverse reactions reported in clinical trials and postmarketing experiences encompass a variety of systems. Gastrointestinal reactions include nausea, epigastric pain, heartburn, diarrhea, and abdominal cramps. Central nervous system effects may manifest as dizziness, headache, and nervousness, with more severe reactions such as depression, confusion, and somnolence noted in some patients. Dermatologic reactions can range from rash and pruritus to more severe conditions like Stevens-Johnson syndrome and toxic epidermal necrolysis.

Patients may also report symptoms affecting special senses, including tinnitus and hearing loss, as well as visual disturbances such as blurred vision and diplopia. Hematologic reactions include neutropenia, agranulocytosis, and thrombocytopenia, with potential bleeding episodes. Metabolic and endocrine effects may present as decreased appetite and gynecomastia, while cardiovascular reactions can include edema and palpitations.

Allergic reactions may occur, presenting as abdominal pain, fever, and anaphylaxis, among others. Miscellaneous effects such as dry eyes and mouth, gingival ulcer, and rhinitis have also been documented.

It is essential for healthcare providers to monitor patients for these adverse reactions and to consider the potential risks associated with the use of this medication, particularly in populations at greater risk.

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. 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 remains unclear, but it is generally not recommended to use ibuprofen and aspirin together 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 should be monitored for signs of lithium toxicity when these medications 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 advised when ibuprofen is used in conjunction with the aforementioned drug classes 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

Pregnancy Category C. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities; however, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Therefore, ibuprofen 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. Healthcare professionals are advised to carefully consider the risks and benefits when prescribing ibuprofen 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. In patients with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion. The administration of an NSAID in these individuals may lead to a dose-dependent reduction in prostaglandin formation, subsequently decreasing renal blood flow and potentially precipitating 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 may experience altered drug metabolism and clearance, necessitating caution when using ibuprofen tablets. It is recommended that liver function tests be monitored periodically in this patient population to assess any changes in liver function that may impact drug handling.

Dosage adjustments may be required based on the severity of liver impairment. In cases of severe hepatic impairment, the use of ibuprofen tablets should be avoided due to the increased risk of adverse effects. Careful consideration and monitoring are essential to ensure patient safety and therapeutic efficacy in individuals with compromised liver function.

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. This stimulus was sufficient to induce respiration. Upon examination, oxygen and parenteral fluids were administered, and a greenish-yellow fluid was aspirated from the stomach, revealing 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. The child was subsequently admitted to intensive care, where sodium bicarbonate, along with dextrose and normal saline infusions, were provided. 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 accidentally 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.

Management of Overdosage 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 should be prioritized, and the use of oral activated charcoal may assist in reducing both absorption and reabsorption of the drug.

In a separate case, a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours reported dizziness, with nystagmus observed during examination. Following 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 symptoms of 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, ibuprofen 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, specifically the closure of the ductus arteriosus, the use of ibuprofen 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.

Postmarketing Experience

In two postmarketing clinical studies, a greater incidence of decreased hemoglobin levels was observed than previously reported. Specifically, a decrease in hemoglobin of 1 gram or more occurred 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.

Anaphylactoid reactions have been reported in patients without known prior exposure to ibuprofen tablets, necessitating emergency assistance in such cases. Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, have also been documented. These serious events may occur without warning.

Aseptic meningitis, accompanied by fever and coma, has been observed on rare occasions in patients undergoing ibuprofen therapy. If signs or symptoms of meningitis develop in a patient receiving ibuprofen tablets, the potential association with ibuprofen should be considered.

Reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of ACE inhibitors. This interaction should be taken into account for patients concurrently using NSAIDs and ACE inhibitors.

While several short-term controlled studies did not demonstrate a significant effect of ibuprofen tablets on prothrombin times or various other clotting factors in individuals on coumarin-type anticoagulants, bleeding incidents have been reported when ibuprofen and other NSAIDs are administered to patients on anticoagulants. Therefore, caution is advised when prescribing ibuprofen tablets to patients receiving anticoagulant therapy.

Patient Counseling

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

Patients should be advised to remain 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, 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 informed that ibuprofen tablets can lead to serious skin side effects, such as 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 vigilant for signs and symptoms such as skin rash, blisters, fever, or other signs of hypersensitivity, including 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.

Healthcare providers should advise patients to be alert for symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms occur.

Patients should 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 symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

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

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

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), in accordance with USP Controlled Room Temperature guidelines. Care should be taken to avoid exposure to excessive heat, specifically temperatures exceeding 40ºC (104ºF). Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Physicians are advised to monitor patients on long-term treatment with NSAIDs for any signs or symptoms of gastrointestinal (GI) bleeding. Additionally, it is recommended that these patients undergo periodic checks of their complete blood count (CBC) and chemistry profile to ensure ongoing safety and efficacy of the treatment.

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. Furthermore, 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 PharmPak, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)