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.

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 individual 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 discomfort.

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 dosing 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 to ibuprofen tablets may be observed within a few days to a week, but is most commonly noted by two weeks. Once a satisfactory response is achieved, the patient's dosage should be reviewed and adjusted as necessary.

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

Contraindications

Ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. Additionally, they should not be administered to individuals who have a history of asthma, urticaria, 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. Furthermore, ibuprofen tablets are contraindicated for the management of perioperative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Cardiovascular effects associated with NSAID use include an increased risk of serious thrombotic events, myocardial infarction, and stroke, which may be fatal. This risk is particularly pronounced in patients with existing cardiovascular disease or risk factors. It is recommended that the lowest effective dose be utilized for the shortest duration necessary, and patients should be educated on recognizing the signs and symptoms of serious cardiovascular events.

NSAIDs may also induce new hypertension or exacerbate pre-existing hypertension. Therefore, it is essential to monitor blood pressure closely during NSAID therapy. Additionally, fluid retention and edema have been reported in some patients, necessitating caution in those with a history of fluid retention or congestive heart failure.

Gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation, can occur with NSAID use and may be fatal. These events can arise unexpectedly, with or without prior warning symptoms. Patients with a history of ulcer disease or gastrointestinal bleeding are at an increased risk for developing gastrointestinal complications.

Long-term NSAID administration may lead to renal injury, particularly in patients with impaired renal function, heart failure, liver dysfunction, those on diuretics or ACE inhibitors, and the elderly. Anaphylactoid reactions can occur even in patients without prior exposure; immediate medical attention is required in such cases. Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis, may also occur without warning. Discontinuation of the medication is advised at the first sign of a skin rash or any indication of hypersensitivity.

In late pregnancy, NSAID use should be avoided due to the risk of premature closure of the ductus arteriosus. It is important to note that ibuprofen does not serve as a substitute for corticosteroids and cannot treat corticosteroid insufficiency. Patients undergoing prolonged corticosteroid therapy should taper their dosage gradually if discontinuing.

Monitoring for borderline elevations in liver tests is recommended, as these may occur in up to 15% of patients. Those exhibiting symptoms suggestive of liver dysfunction should be evaluated for potential severe hepatic reactions. Anemia may develop in patients on long-term NSAID treatment; therefore, hemoglobin or hematocrit levels should be checked if signs of anemia arise. Patients with asthma should be assessed for aspirin-sensitive asthma, as ibuprofen is contraindicated in such cases.

Blurred vision and changes in color vision have been reported; if these symptoms occur, the patient should discontinue use and seek an ophthalmologic evaluation. Aseptic meningitis has been observed in rare instances, and clinicians should consider this diagnosis if relevant signs or symptoms develop.

Laboratory tests should include regular blood pressure monitoring during NSAID treatment, hemoglobin or hematocrit checks for patients on long-term therapy if signs of anemia develop, and liver function evaluations for those with symptoms or abnormal liver test results.

Emergency medical assistance should be sought immediately in the event of an anaphylactoid reaction. Patients are advised to discontinue use and contact their healthcare provider at the first appearance of a skin rash or any other sign of hypersensitivity. If clinical signs and symptoms indicative of liver disease develop, ibuprofen should be discontinued promptly.

Side Effects

Patients may experience a range of adverse reactions while using this medication, which can be categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular and gastrointestinal risks. NSAIDs are associated with an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may escalate with prolonged use, particularly in patients with existing cardiovascular disease or risk factors. Additionally, NSAIDs can lead to serious gastrointestinal events such as bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal complications may occur at any time during treatment and without warning symptoms, with elderly patients being at greater risk.

Gastrointestinal adverse reactions commonly reported include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal issues may involve nausea and vomiting, indigestion, constipation, abdominal cramps or pain, and fullness of the gastrointestinal tract, characterized by bloating and flatulence. More severe gastrointestinal reactions, such as gastric or duodenal ulcers with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests, and pancreatitis, have also been documented.

Central nervous system reactions may include dizziness, headache, and nervousness. More serious effects such as depression, insomnia, confusion, emotional liability, somnolence, and rare occurrences of aseptic meningitis with fever and coma have been reported. Patients may also experience paresthesias, hallucinations, dream abnormalities, and pseudo-tumor cerebri.

Dermatologic reactions can range from mild to severe, including rash (maculopapular type), pruritus, vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia. Severe skin reactions such as toxic epidermal necrolysis and photoallergic skin reactions have also been noted.

Adverse reactions affecting the special senses include tinnitus, hearing loss, amblyopia (blurred and/or diminished vision), conjunctivitis, diplopia, optic neuritis, and cataracts.

Hematologic adverse reactions may involve neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, and decreases in hemoglobin and hematocrit. Bleeding episodes, such as epistaxis and menorrhagia, have also been reported.

Metabolic and endocrine reactions include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

Cardiovascular reactions may manifest as edema, fluid retention (which generally responds promptly to drug discontinuation), congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (including sinus tachycardia and sinus bradycardia).

Allergic reactions can present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting; anaphylaxis; bronchospasm; serum sickness; lupus erythematosus syndrome; Henoch-Schonlein vasculitis; and angioedema.

Renal adverse reactions may include acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, hematuria, and renal papillary necrosis.

Miscellaneous adverse reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

In clinical trials, reported side effects were higher at doses of 3200 mg/day compared to doses of 2400 mg or less per day in patients with rheumatoid arthritis, although the increases in incidence were slight and remained within the ranges reported. Additionally, aseptic meningitis with fever and coma has been observed on rare occasions in patients undergoing ibuprofen therapy.

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 monitored closely 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 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 should be closely 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 ibuprofen 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 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 is recommended to ensure the safety and efficacy of treatment in geriatric patients.

Pregnancy

Pregnancy Category C indicates that there are no adequate and well-controlled studies in pregnant women, and while reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities, animal reproduction studies are not always predictive of human response. Therefore, Motrin should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Healthcare professionals should be aware of the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, particularly the risk of closure of the ductus arteriosus. Consequently, the use of Motrin during late pregnancy should be avoided to mitigate potential adverse fetal outcomes.

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 where renal prostaglandins play a compensatory role in maintaining renal perfusion, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow. This reduction can precipitate overt renal decompensation, particularly in patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.

Due to the lack of controlled clinical study data regarding the use of ibuprofen tablets in patients with advanced renal disease, treatment with ibuprofen 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. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no 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 and management strategies can vary significantly based on the amount ingested and the patient's age and weight.

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, which was sufficient to induce respiration. Initial management included the administration of oxygen and parenteral fluids. Gastric aspiration yielded a greenish-yellow fluid, 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. Following admission to intensive care, sodium bicarbonate, along with 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 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 post-ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

Management Strategies

For adults, a case involving a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours reported dizziness and nystagmus. After hospitalization, he received parenteral hydration and underwent three days of bed rest, ultimately recovering without any reported sequelae.

In instances of acute overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage; however, if more than one hour has passed since ingestion, the likelihood of recovering significant amounts of the drug diminishes. Given the acidic nature of ibuprofen and its urinary excretion, administering alkali and inducing diuresis may be beneficial. Supportive measures should be prioritized, and the use of oral activated charcoal may assist in reducing both 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, 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 observed than previously reported. Specifically, a decrease in hemoglobin of 1 gram or more occurred in 17.1% of 193 patients taking 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients receiving 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 reported in patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets. This may result from 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.

NSAIDs are known to inhibit platelet aggregation and may prolong bleeding time in some patients. While their effect on platelet function is quantitatively less, shorter in duration, and reversible compared to aspirin, patients receiving ibuprofen tablets who may be adversely affected by changes in platelet function, such as those with coagulation disorders or those on anticoagulants, should be closely monitored.

Aseptic meningitis, accompanied by fever and coma, has been reported on rare occasions in patients undergoing ibuprofen therapy. This condition is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, but it has also been documented in individuals without underlying chronic diseases. If signs or symptoms of meningitis develop in a patient taking ibuprofen tablets, the potential association with the medication should be evaluated.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal, have been associated with NSAIDs, including ibuprofen tablets. These serious reactions may occur without warning. Patients should be informed of the signs and symptoms of serious skin manifestations, and the use of the drug should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity.

Reports indicate that NSAIDs may reduce the antihypertensive effect of ACE inhibitors. This interaction should be considered in patients taking NSAIDs concurrently with ACE inhibitors.

Several short-term controlled studies have not demonstrated a significant effect of ibuprofen tablets on prothrombin times or various other 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 administering ibuprofen tablets to these patients. The combined effects of warfarin and NSAIDs on gastrointestinal bleeding are synergistic, resulting in a higher risk of serious gastrointestinal bleeding for users of both medications compared to those using either drug alone.

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. It is important for patients 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 instructed to remain vigilant for signs and symptoms such as chest pain, shortness of breath, weakness, and slurring of speech, and to seek medical advice if they observe any of these indicative signs.

Additionally, patients should be informed that ibuprofen tablets can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects, including ulcers and bleeding, which may also result in hospitalization or death. Patients should be advised to be alert for signs and symptoms of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis, and to consult their healthcare provider if they experience any of these symptoms.

Healthcare providers should also communicate the risk of 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. Patients should be advised to monitor for signs and symptoms such as skin rash, blisters, fever, or other hypersensitivity reactions like itching. They should be instructed to discontinue the medication immediately and contact their physician if any rash develops.

Patients should promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider. Furthermore, they should be informed about the warning signs 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.

It is crucial for patients to recognize the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat, and to seek emergency help if these symptoms arise. Lastly, 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 National Drug Code (NDC) specifications. It should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), as defined by the United States Pharmacopeia (USP) guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Physicians should monitor patients on long-term NSAID treatment for signs or symptoms of gastrointestinal (GI) bleeding and periodically check complete blood count (CBC) and chemistry profiles. If patients exhibit clinical signs consistent with liver or renal disease, systemic manifestations such as eosinophilia or rash, or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued.

Patients should be counseled on the serious cardiovascular side effects associated with ibuprofen, including myocardial infarction (MI) and stroke, emphasizing the importance of follow-up. They should be vigilant for signs of GI discomfort, serious GI side effects like ulcerations and bleeding, and serious skin reactions, instructing them to stop the medication immediately if a rash develops. Additionally, patients should report any unexplained weight gain or edema, be aware of hepatotoxicity warning signs, and seek medical assistance if these occur. Patients should also be informed about the signs of an anaphylactoid reaction and the need for emergency help if such symptoms arise. It is advised to avoid ibuprofen in late pregnancy due to the risk of premature closure of the ductus arteriosus.

FDA Insert (PDF)

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

View full prescribing information (PDF)