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 of 74-77°C. It is characterized by very slight solubility in water (less than 1 mg/mL) and is readily soluble in organic solvents such as ethanol and acetone. The structural formula of ibuprofen is provided below.

These tablets are classified as a nonsteroidal anti-inflammatory drug (NSAID) and are available in dosages of 400 mg, 600 mg, and 800 mg for oral administration. The formulation includes several inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, talc, 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 administered as 300 mg four times daily (qid) or as 400 mg, 600 mg, or 800 mg three to four times daily (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 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. 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 begin 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, the use of Ibuprofen is not recommended for individuals who have a history of asthma, urticaria, or allergic-type reactions following the administration 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 peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Patients receiving NSAIDs, including ibuprofen, should be aware of the potential for serious cardiovascular and gastrointestinal risks associated with their use.

Cardiovascular 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 those with risk factors for cardiovascular conditions. It is crucial for healthcare professionals to evaluate the cardiovascular status of patients prior to initiating NSAID therapy.

Contraindications Ibuprofen tablets are contraindicated for the treatment of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery. This contraindication should be strictly adhered to in clinical practice to avoid potential complications.

Gastrointestinal Risks The use of NSAIDs is linked to an increased risk of serious gastrointestinal adverse events, such as bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These events may occur at any time during treatment and can arise without warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal complications, necessitating careful monitoring.

Monitoring Parameters Healthcare professionals should monitor patients for signs or symptoms indicative of gastrointestinal bleeding. For those on long-term NSAID therapy, it is recommended that a complete blood count (CBC) and chemistry profile be assessed periodically to detect any potential adverse effects. Should any clinical signs or symptoms suggestive of liver or renal disease develop, or if systemic manifestations such as eosinophilia or rash occur, or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued immediately.

In summary, vigilance in monitoring and adherence to contraindications is essential for the safe use of ibuprofen and other NSAIDs, particularly in at-risk populations.

Side Effects

Patients may experience a range of adverse reactions while using this medication, categorized by incidence and seriousness.

Serious adverse reactions include an increased risk of cardiovascular thrombotic events, 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, there is a significant risk of serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. Such events may occur unexpectedly at any time during treatment, with elderly patients being at a heightened risk.

Common adverse reactions, occurring in greater than 1% but less than 3% of patients, encompass gastrointestinal symptoms such as nausea, epigastric pain, heartburn, diarrhea, abdominal distress, and constipation. Central nervous system effects may include dizziness, headache, and nervousness. Dermatologic reactions such as rash and pruritus, as well as tinnitus in the special senses, have also been reported. Metabolic and endocrine effects may manifest as decreased appetite, while cardiovascular reactions can include edema and fluid retention, which typically resolve upon discontinuation of the drug.

Less common adverse reactions, with a precise incidence unknown but occurring in less than 1% of patients, include serious gastrointestinal complications such as gastric or duodenal ulcers with bleeding or perforation, gastrointestinal hemorrhage, and pancreatitis. Central nervous system reactions may involve depression, insomnia, confusion, emotional lability, and aseptic meningitis. Dermatologic reactions can include severe conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Hematologic issues may present as neutropenia, agranulocytosis, and thrombocytopenia. Cardiovascular concerns may involve congestive heart failure in patients with marginal cardiac function, elevated blood pressure, and palpitations. Allergic reactions can manifest as anaphylaxis or bronchospasm, while renal complications may include acute renal failure and hematuria.

Additional adverse reactions with a potential causal relationship, though with a precise incidence unknown, include bleeding episodes such as epistaxis and menorrhagia, gynecomastia, and hypoglycemic reactions. Cardiovascular arrhythmias, dermatologic photoallergic skin reactions, and special senses issues such as conjunctivitis and diplopia have also been noted.

Patients should be monitored for these adverse reactions, and any concerning symptoms should prompt immediate medical evaluation.

Drug Interactions

Concomitant use of certain medications with ibuprofen may lead to significant drug interactions, which can affect therapeutic outcomes and safety. The following interactions have been identified:

Pharmacodynamic Interactions

• ACE-Inhibitors: Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may reduce the antihypertensive effect of ACE-inhibitors. Clinicians should consider this interaction when prescribing NSAIDs to patients already receiving ACE-inhibitors.

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

• Warfarin-Type Anticoagulants: While short-term studies have not demonstrated a significant effect of ibuprofen on prothrombin times in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of NSAIDs and anticoagulants may synergistically elevate the risk of serious gastrointestinal bleeding. Caution is advised when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

• Aspirin: Co-administration of ibuprofen with aspirin may reduce the protein binding of aspirin, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction remains unclear, but the concurrent use of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

• Lithium: Ibuprofen has been associated with elevated plasma lithium levels and decreased renal clearance of lithium. In a study, the mean minimum lithium concentration increased by 15%, and renal clearance decreased by 19% during concurrent administration. Patients receiving both ibuprofen and lithium should be monitored closely for signs of lithium toxicity.

• Methotrexate: NSAIDs, including ibuprofen, may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is warranted when these medications are used together.

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 minimal interaction 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, specifically those aged 65 years and older. Due to the potential for altered pharmacokinetics and increased sensitivity to medications in this population, careful consideration of dosage adjustments and monitoring is essential. Healthcare providers are advised to assess the individual health status and comorbidities of geriatric patients to ensure safe and effective treatment. Regular evaluation of therapeutic outcomes and adverse effects is recommended to mitigate risks associated with medication use in this age group.

Pregnancy

Pregnant patients should be aware that ibuprofen tablets are 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. Currently, there are no adequate and well-controlled studies in pregnant women.

The use of ibuprofen during pregnancy should be considered only if the potential benefits justify the potential risks to the fetus. Special caution is warranted during late pregnancy due to the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, particularly the risk of closure of the ductus arteriosus. Therefore, the use of ibuprofen should be avoided in this period.

Additionally, studies in rats have indicated that NSAIDs, including ibuprofen, may lead to 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. Healthcare professionals should carefully evaluate the risks and benefits before 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 breastfeeding or discontinue the drug.

Renal Impairment

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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 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 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 μg/mL approximately 8½ hours after ingestion, and by 12 hours, the child appeared to have fully recovered.

In another instance, two children, each weighing approximately 10 kg, ingested about 120 mg/kg of ibuprofen. Remarkably, neither child exhibited signs of acute intoxication or any late sequelae. One child had a blood level of 700 μg/mL 90 minutes after ingestion, which is approximately ten times the peak levels observed in absorption-excretion studies.

Management of Overdosage For acute ibuprofen overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage, although 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 beneficial. Supportive measures should be prioritized, and the use of oral activated charcoal can be considered to reduce both absorption and reabsorption of the drug.

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

In summary, while ibuprofen overdosage can lead to significant clinical symptoms, prompt medical intervention and supportive care can result in favorable outcomes.

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 tablets 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.

Patient Counseling

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

Healthcare providers should advise patients that ibuprofen tablets, like other NSAIDs, may cause serious cardiovascular (CV) side effects, including myocardial infarction (MI) or stroke, which could result in hospitalization or even death. Patients should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, or slurring of speech, and should seek medical advice if they observe any indicative signs or symptoms. It is important for patients to understand the significance of this follow-up.

Patients should also be made aware that ibuprofen tablets can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may lead to hospitalization or death. Serious GI tract ulcerations and bleeding can occur without warning symptoms; therefore, patients should be vigilant for signs such as epigastric pain, dyspepsia, melena, or hematemesis. They should be instructed to seek medical advice if they experience any of these symptoms and understand the importance of this follow-up.

Additionally, patients should be informed that ibuprofen tablets can lead to serious skin side effects, including 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 alert for signs such as skin rash, blisters, fever, or other hypersensitivity symptoms 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.

Patients should promptly report any signs or symptoms of unexplained weight gain or edema to their physicians. They should also be informed about the warning signs and symptoms of hepatotoxicity, which 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.

Furthermore, patients should be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat. In such cases, they should be instructed to seek immediate emergency help.

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

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Clinicians are advised to monitor 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 complications. Additionally, ibuprofen tablets should be discontinued if patients exhibit clinical signs and symptoms indicative of liver or renal disease, experience systemic manifestations such as eosinophilia or rash, or if abnormal liver tests persist or worsen.

FDA Insert (PDF)

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

View full prescribing information (PDF)