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 demonstrating ready solubility 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 are advised to utilize the lowest effective dose of ibuprofen tablets for the shortest duration that aligns with individual patient treatment goals. Following the initial therapy, the dose and frequency should be adjusted based on the patient's response and specific needs.

For the management of rheumatoid arthritis and osteoarthritis, the recommended daily dosage ranges from 1200 mg to 3200 mg. This can be administered as 300 mg four times daily, or as 400 mg, 600 mg, or 800 mg three to four times daily. It is essential to tailor the dosage to each patient, with adjustments made according to the severity of symptoms. Notably, patients with rheumatoid arthritis may require higher doses compared to those with osteoarthritis.

For the treatment of mild to moderate pain, a dosage of 400 mg may be given every 4 to 6 hours as needed for pain relief. In cases of dysmenorrhea, a dosage of 400 mg every 4 hours may be administered as necessary for pain relief.

The total daily dose should not exceed 3200 mg. In instances where gastrointestinal complaints arise, it is recommended to administer ibuprofen tablets with meals or milk to mitigate these effects. The smallest effective dose that provides acceptable control should always be employed.

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

Non-steroidal anti-inflammatory drugs (NSAIDs), including Ibuprofen Tablets, are associated with an increased risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk may manifest early in treatment and is likely to escalate with prolonged use. Ibuprofen Tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs can also lead to significant gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which may be fatal. These serious adverse events can occur at any time, with or without warning symptoms. Patients with a recent myocardial infarction (MI) should avoid the use of Ibuprofen Tablets unless the anticipated benefits outweigh the risks of recurrent cardiovascular thrombotic events. Additionally, NSAIDs may contribute to the onset of new hypertension or exacerbate preexisting hypertension. In patients with heart failure, the use of Ibuprofen Tablets may increase the risk of myocardial infarction, hospitalization for heart failure, and mortality.

Anaphylactoid reactions can occur in patients without prior exposure to ibuprofen. In such cases, emergency medical assistance should be sought immediately. Furthermore, NSAIDs have been linked to serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.

Ibuprofen Tablets are not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of the underlying condition. For patients on prolonged corticosteroid therapy, a gradual tapering of the corticosteroid dosage is recommended if discontinuation is necessary.

Patients undergoing long-term NSAID treatment should have their hemoglobin or hematocrit levels monitored if they exhibit any signs or symptoms of anemia. Additionally, those receiving Ibuprofen Tablets who may be adversely affected by changes in platelet function should be closely monitored.

Physicians should remain vigilant for signs or symptoms of GI bleeding in patients on long-term NSAID therapy. Regular monitoring of complete blood count (CBC) and chemistry profiles is advised for these patients. If clinical signs and symptoms indicative of liver or renal disease develop, or if abnormal liver tests persist or worsen, Ibuprofen Tablets should be discontinued.

Patients should seek emergency medical help if an anaphylactoid reaction occurs. Furthermore, Ibuprofen Tablets should be discontinued at the first sign of skin rash or any other indication of hypersensitivity. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations such as eosinophilia or rash occur, patients should stop taking the medication and contact their healthcare provider.

Side Effects

Patients receiving treatment with non-steroidal anti-inflammatory drugs (NSAIDs) may experience a range of adverse reactions, which can be 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 escalate with prolonged use. Additionally, NSAIDs are associated with a heightened risk of serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal complications can occur at any time during therapy and may present without warning symptoms, particularly in elderly patients who are at greater risk.

Common gastrointestinal adverse reactions reported in clinical trials include nausea, epigastric pain, heartburn, diarrhea, and abdominal distress. Other gastrointestinal issues such as constipation, abdominal cramps, and bloating have also been noted. Serious gastrointestinal complications, including gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis, have been documented.

Central nervous system reactions may include dizziness, headache, and nervousness, with more serious effects such as depression, insomnia, confusion, and somnolence reported. Rarely, aseptic meningitis, hallucinations, and pseudo-tumor cerebri have been observed.

Dermatologic reactions can range from mild rashes and pruritus to severe conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Other skin reactions include vesiculobullous eruptions and photoallergic skin reactions.

Adverse reactions affecting special senses include tinnitus, hearing loss, and blurred vision, with more serious conditions such as optic neuritis and cataracts noted.

Hematologic adverse reactions include neutropenia, agranulocytosis, and thrombocytopenia, with bleeding episodes such as epistaxis and menorrhagia also reported.

Metabolic and endocrine reactions may involve decreased appetite, gynecomastia, and hypoglycemic reactions. Cardiovascular effects can include edema, fluid retention, congestive heart failure in patients with marginal cardiac function, and arrhythmias.

Allergic reactions may present as abdominal pain, fever, chills, and anaphylaxis, with other serious conditions such as serum sickness and angioedema reported.

Renal adverse reactions include acute renal failure, decreased creatinine clearance, and hematuria, with renal papillary necrosis also noted.

Miscellaneous reactions such as dry eyes and mouth, gingival ulcer, and rhinitis have been reported.

In clinical trials, the incidence of reported side effects was higher at doses of 3200 mg/day compared to doses of 2400 mg or less, although the increases were slight and remained within the ranges previously documented. Reactions occurring in 3% to 9% of patients treated with ibuprofen are marked, while those occurring in less than 3% are unmarked. Reactions are classified under “Probable Causal Relationship (PCR)” if there has been one positive rechallenge or if three or more cases occur that might be causally related. Conversely, reactions are classified under “Causal Relationship Unknown” if seven or more events have been reported but do not meet the criteria for PCR.

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 aspirin, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction is unclear, but the concurrent use of ibuprofen and aspirin is generally not recommended 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, 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 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. Therefore, this medication 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, use 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 administration of an NSAID 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 this population. If initiation of ibuprofen tablet therapy is deemed necessary, close monitoring of the patient's renal function is advised.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when administered NSAIDs. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals where renal prostaglandins play a critical role in maintaining renal perfusion. In patients with compromised liver function, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate overt renal decompensation.

Patients with hepatic impairment are at an increased risk for renal toxicity, especially those who also have impaired renal function, heart failure, or are taking diuretics and ACE inhibitors. The elderly population may also be particularly vulnerable. It is recommended that healthcare providers closely monitor renal function in these patients during NSAID therapy. Should any signs of renal decompensation occur, discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state. Therefore, careful consideration and monitoring are essential when prescribing NSAIDs to patients with hepatic impairment.

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 examination, oxygen and parenteral fluids were administered, and a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen. Two hours post-ingestion, the child's condition appeared stable; however, she continued to respond solely to painful stimuli and experienced intermittent 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 showed complete recovery.

In two additional reported 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 was noted. Following hospitalization, the patient 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, it is important to note 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. Supportive measures should be employed, and the use of oral activated charcoal may assist 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, 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, use during late pregnancy should be avoided.

In studies involving rats, the administration of NSAIDs has been associated with an increased incidence of dystocia, delayed parturition, and decreased pup survival. The effects of ibuprofen tablets on labor and delivery in pregnant women remain unknown.

Postmarketing Experience

In two postmarketing clinical studies, a greater incidence of decreased hemoglobin levels was observed compared to previous reports. 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.

Furthermore, reported side effects were found to be higher at doses of 3200 mg per day compared to doses of 2400 mg or less per day in clinical trials involving patients with rheumatoid arthritis. Although the increases in incidence were slight, they remained within the ranges previously reported.

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 advise patients to be vigilant for symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately. It is important to communicate that ibuprofen, like other NSAIDs, may cause serious cardiovascular side effects, such as myocardial infarction or stroke, which could lead to hospitalization or even death. Although serious cardiovascular events can occur without warning, patients should be made aware of the signs and symptoms to monitor and the importance of seeking medical advice if they observe any indicative signs.

Additionally, patients should be informed that ibuprofen can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, such as ulcers and bleeding, which may also result in hospitalization or death. Patients should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should be instructed to seek medical advice if they experience any of these symptoms.

Healthcare providers should also discuss the potential for serious skin side effects associated with ibuprofen, such as 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 of skin rash, blisters, fever, or other hypersensitivity reactions, such as itching, and to stop the medication immediately and contact their physician if any rash develops.

Patients should be made aware of the symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema, and should be instructed to contact their healthcare provider if such symptoms occur.

It is crucial to inform patients about the warning signs and symptoms of hepatotoxicity, such as nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms. If these symptoms occur, patients should be instructed to discontinue therapy and seek immediate medical attention.

Patients should also be educated on the signs of an anaphylactoid reaction, including difficulty breathing and swelling of the face or throat, and should be advised to seek emergency help if these symptoms arise.

Finally, healthcare providers should inform patients that ibuprofen should be avoided in late pregnancy, as it may cause 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 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), to maintain product integrity.

Additional Clinical Information

Physicians are advised to monitor patients on long-term treatment with NSAIDs for any signs or symptoms indicative of gastrointestinal bleeding. Additionally, it is recommended that these patients undergo periodic evaluations 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 suggestive 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 Virtue Rx, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)