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. 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 each 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. This can be achieved through various dosing schedules, 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 always be employed.

For the treatment of mild to moderate pain, a dosage of 400 mg may be administered every 4 to 6 hours as necessary for pain relief. In the case of dysmenorrhea, ibuprofen tablets should be given at the onset of pain, starting with a dose of 400 mg every 4 hours as needed 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 other 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 in the context of coronary artery bypass graft (CABG) surgery.

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. It is important to note that ibuprofen tablets are contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery.

In addition to cardiovascular risks, NSAIDs can lead to serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which may also be fatal. These gastrointestinal complications can occur at any time during treatment and may arise without warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal events and should be monitored closely.

Ibuprofen tablets are not intended to replace corticosteroids or to address corticosteroid insufficiency. Abrupt cessation of corticosteroids can result in exacerbation of the underlying condition. Therefore, patients who have been on prolonged corticosteroid therapy should have their medication tapered gradually if discontinuation is deemed necessary.

The pharmacological effects of ibuprofen in reducing fever and inflammation may obscure diagnostic signs that are critical for identifying complications in presumed noninfectious, painful conditions. Healthcare professionals should remain vigilant in assessing patients for these complications.

Due to the potential for serious gastrointestinal ulcerations and bleeding, physicians should actively monitor patients for any signs or symptoms indicative of gastrointestinal bleeding. For patients on long-term NSAID therapy, it is recommended that a complete blood count (CBC) and chemistry profile be conducted periodically. Should any clinical signs or symptoms suggestive of liver or renal disease arise, or if systemic manifestations such as eosinophilia or rash occur, or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued immediately.

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 cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. This risk is particularly concerning as it may arise early in treatment and can increase with prolonged use. 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. These gastrointestinal complications can occur at any time during treatment, often without warning symptoms, and elderly patients are at a heightened risk.

Common gastrointestinal adverse reactions 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 a sensation of fullness in the gastrointestinal tract, such as bloating and flatulence. More severe gastrointestinal complications, 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 observed.

Central nervous system reactions may include dizziness, headache, and nervousness, with more serious effects such as depression, insomnia, confusion, emotional liability, somnolence, and aseptic meningitis with fever and coma. Other reported symptoms include paresthesias, hallucinations, dream abnormalities, and pseudo-tumor cerebri.

Dermatologic reactions can range from rash (including maculopapular types) and pruritus to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, and alopecia. Rare but serious skin reactions include toxic epidermal necrolysis and photoallergic skin reactions.

Hematologic adverse reactions include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), and thrombocytopenia with or without purpura. Patients may also experience eosinophilia and decreases in hemoglobin and hematocrit, as well as bleeding episodes such as epistaxis and menorrhagia.

Metabolic and endocrine reactions may manifest as decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis. Cardiovascular reactions can include edema and fluid retention, which generally respond promptly to drug discontinuation, as well as congestive heart failure in patients with marginal cardiac function, elevated blood pressure, palpitations, and arrhythmias (sinus tachycardia and sinus bradycardia).

Allergic reactions may present as a syndrome of abdominal pain, fever, chills, nausea, and vomiting, as well as anaphylaxis and bronchospasm. Other allergic conditions reported include 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 reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

Healthcare providers should monitor patients for these adverse reactions and consider the risk factors associated with their occurrence.

Drug Interactions

Concomitant use of certain medications with ibuprofen may lead to significant drug interactions, which can affect therapeutic outcomes and patient 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 monitor blood pressure in patients receiving both medications and consider alternative analgesics if necessary.

• Aspirin:

  • Ibuprofen can interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered before aspirin. This interaction is significant even with a once-daily regimen of ibuprofen at 400 mg.

  • To mitigate this interaction, immediate-release low-dose aspirin should be taken at least 2 hours prior to ibuprofen. However, this timing does not apply to enteric-coated low-dose aspirin.

  • There is an increased risk of cardiovascular events due to this interaction. For patients on low-dose aspirin for cardioprotection who require analgesics, alternative NSAIDs that do not affect aspirin's antiplatelet effect or non-NSAID analgesics should be considered.

  • Co-administration of ibuprofen with aspirin may reduce ibuprofen's protein binding, although its clearance remains unchanged. The clinical significance of this interaction is not fully understood, but concomitant use is generally not recommended due to potential adverse effects.

• Diuretics: Ibuprofen may diminish the natriuretic effect of diuretics such as furosemide and thiazides, likely due to inhibition of renal prostaglandin synthesis. Patients should be closely monitored for signs of renal failure and to ensure diuretic efficacy during concurrent therapy.

• Lithium: Ibuprofen has been shown to elevate plasma lithium levels and decrease renal clearance of lithium. Specifically, a study indicated a 15% increase in mean minimum lithium concentration and a 19% reduction in renal clearance. Careful monitoring for signs of lithium toxicity is advised when these drugs are used together.

• Methotrexate: NSAIDs may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is warranted when administering NSAIDs alongside methotrexate.

• Warfarin-type Anticoagulants: While short-term studies have not demonstrated significant effects of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of warfarin and NSAIDs can lead to a synergistic effect on gastrointestinal bleeding risk. Physicians should exercise caution when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

• H-2 Antagonists: Co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine does not significantly affect ibuprofen serum concentrations, indicating no major pharmacokinetic interaction.

In summary, careful consideration and monitoring are essential 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

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

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy is associated with significant risks, particularly when used after approximately 20 weeks of gestation. The administration of NSAIDs at around 30 weeks of gestation or later can lead to premature closure of the fetal ductus arteriosus, which may result in serious fetal complications. Additionally, NSAID use during this period has been linked to fetal renal dysfunction, leading to oligohydramnios and, in some cases, neonatal renal impairment.

To mitigate these risks, it is recommended that the use of ibuprofen tablets be limited in dose and duration between 20 and 30 weeks of gestation, and avoided entirely after 30 weeks. If NSAID treatment is deemed necessary after 20 weeks, it should be restricted to the lowest effective dose for the shortest duration possible. In cases where ibuprofen treatment extends beyond 48 hours, monitoring with ultrasound for oligohydramnios is advised. Should oligohydramnios be detected, discontinuation of ibuprofen tablets is warranted, followed by appropriate clinical follow-up.

While observational studies have provided inconclusive data regarding other potential embryo-fetal risks associated with NSAID use in the first and second trimesters, the background rate of major malformations in the general U.S. population is 2-4%, with a pregnancy loss rate of 15-20%, regardless of drug exposure. Animal studies have not demonstrated developmental abnormalities with ibuprofen; however, these studies are not always predictive of human outcomes.

There are no adequate and well-controlled studies in pregnant women, and ibuprofen should only be used during pregnancy if the potential benefits justify the risks to the fetus. Prostaglandins play a crucial role in various reproductive processes, and animal studies indicate that prostaglandin synthesis inhibitors like ibuprofen may impair kidney development and increase pre- and post-implantation loss.

Published literature indicates that adverse outcomes, such as neonatal renal dysfunction, may occur following maternal NSAID use, with some cases requiring invasive interventions. However, methodological limitations in these studies, including the absence of control groups and variability in drug exposure, hinder the establishment of a reliable risk estimate for adverse fetal and neonatal outcomes. Furthermore, the generalizability of reported risks to full-term infants remains uncertain, as most safety data involve preterm infants.

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

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 available prescribing information.

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 patient 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 presence. Two hours post-ingestion, the child's condition appeared stable; however, she continued to respond solely to painful stimuli and exhibited periods of apnea lasting 5 to 10 seconds. The patient 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 appeared to have fully recovered.

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 should be noted that minimal drug recovery is expected if more than one hour has passed since ingestion. Given the acidic nature of ibuprofen and its urinary excretion, the administration of alkali and the induction of diuresis may be theoretically beneficial. Supportive measures should be implemented, and the use of oral activated charcoal may assist in reducing both the absorption and reabsorption of ibuprofen tablets.

Nonclinical Toxicology

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen tablets, during pregnancy, particularly after approximately 20 weeks of gestation, has been associated with an increased risk of fetal renal dysfunction, leading to oligohydramnios and, in some instances, neonatal renal impairment. These adverse effects may manifest after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours following the initiation of NSAID therapy. While oligohydramnios is often reversible upon discontinuation of treatment, prolonged cases may result in complications such as limb contractures and delayed lung maturation. In certain postmarketing reports, instances of impaired neonatal renal function necessitated invasive interventions, including exchange transfusion or dialysis.

Data from observational studies regarding potential embryo-fetal risks associated with NSAID use during the first or second trimesters of pregnancy remain inconclusive. In animal reproductive studies conducted in rats and rabbits, no evidence of developmental abnormalities was observed; however, it is important to note that animal reproduction studies do not always predict human responses. Administration of prostaglandin synthesis inhibitors, such as ibuprofen, has been linked to increased pre- and post-implantation loss. Prostaglandins play a critical role in fetal kidney development, and published animal studies indicate that the use of prostaglandin synthesis inhibitors at clinically relevant doses may impair kidney development.

No controlled clinical study data are available regarding the use of ibuprofen tablets in patients with advanced renal disease. Consequently, the use of ibuprofen tablets is not recommended in this patient population. If therapy with ibuprofen tablets is deemed necessary, close monitoring of renal function is advised.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of ibuprofen tablets, reported voluntarily or through surveillance programs. Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen, necessitating immediate medical attention in such cases.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, with the potential for these events to be fatal and to occur without warning. Additionally, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been documented in patients taking NSAIDs, including ibuprofen, with some cases resulting in fatal or life-threatening outcomes.

In two postmarketing clinical studies, a higher incidence of decreased hemoglobin levels was observed than previously reported. Specifically, a decrease of 1 gram or more in hemoglobin was noted in 17.1% of 193 patients taking 1600 mg of ibuprofen daily for osteoarthritis, and in 22.8% of 189 patients taking 2400 mg daily for rheumatoid arthritis. Positive stool occult blood tests and elevated serum creatinine levels were also recorded in these studies.

Observational studies from the Danish National Registry indicated that patients treated with NSAIDs in the post-myocardial infarction (MI) period faced an increased risk of reinfarction, cardiovascular-related death, and all-cause mortality, beginning within the first week of treatment. The incidence of death in the first year post-MI was reported at 20 per 100 person-years among NSAID-treated patients, compared to 12 per 100 person-years in those not exposed to NSAIDs.

Furthermore, some cases of neonatal renal dysfunction associated with ibuprofen use required invasive treatments, such as exchange transfusion or dialysis.

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 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. Patients should be made aware 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 alert for the signs and symptoms mentioned and seek 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 vigilant for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they experience any of these symptoms. The importance of follow-up regarding these potential side effects should be emphasized.

Patients should be advised to discontinue ibuprofen immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible. They should also be alert for symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or edema, and to contact their healthcare provider if such symptoms occur.

It is crucial for patients to 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 occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should also be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing or swelling of the face or throat, and should be instructed to seek immediate emergency help if these symptoms arise.

Pregnant women should be advised to avoid the use of ibuprofen and other NSAIDs starting at 30 weeks gestation due to the risk of premature closure of the fetal ductus arteriosus. If treatment with ibuprofen is necessary for a pregnant woman between approximately 20 to 30 weeks gestation, she should be informed that monitoring for oligohydramnios may be required if treatment continues for longer than 48 hours.

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), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Clinicians should be vigilant in monitoring patients for signs or symptoms of gastrointestinal (GI) bleeding, as there is a risk of serious GI tract ulcerations and bleeding associated with the use of ibuprofen. For patients undergoing long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that complete blood counts (CBC) and chemistry profiles be checked periodically to assess for potential adverse effects.

In cases where patients exhibit clinical signs and symptoms indicative of liver or renal disease, or if systemic manifestations such as eosinophilia or rash occur, ibuprofen tablets should be discontinued. Additionally, if abnormal liver tests persist or worsen, immediate cessation of the medication is advised.

FDA Insert (PDF)

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

View full prescribing information (PDF)