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 formulated for oral administration in dosages of 400 mg, 600 mg, and 800 mg. The formulation includes several inactive ingredients: silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycols, 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, as well as 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 these effects.

For the management of rheumatoid arthritis and osteoarthritis, 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). It is important to tailor the dose to each patient, which may involve lowering or raising the dosage based on the severity of symptoms at the initiation of therapy or in response to treatment.

Generally, 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.

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

Warnings and Precautions

Nonsteroidal 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 present without warning symptoms. Elderly patients are particularly vulnerable to these serious gastrointestinal events.

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 receiving 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 monitor patients for signs or symptoms of gastrointestinal bleeding, particularly in those on long-term NSAID therapy. Regular monitoring of complete blood count (CBC) and chemistry profiles is recommended for these patients. If any clinical signs or symptoms indicative 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.

In cases of an anaphylactoid reaction, immediate emergency medical assistance should be sought. Patients should be educated on the signs and symptoms of serious skin reactions. They must be advised to discontinue ibuprofen tablets at the first indication of a skin rash or any other signs of hypersensitivity and to seek immediate evaluation.

Side Effects

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

Serious adverse reactions include cardiovascular thrombotic events, such as myocardial infarction and stroke, which can be fatal. The risk of these events may increase with the duration of use and can occur early in treatment. Additionally, there is a significant risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal events may occur at any time during treatment and without warning symptoms, with elderly patients being at greater risk.

Gastrointestinal reactions are common and may include nausea, epigastric pain, heartburn, diarrhea, abdominal distress, vomiting, indigestion, constipation, and abdominal cramps or pain. More severe gastrointestinal issues 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 reported.

Central nervous system effects may manifest as dizziness, headache, and nervousness. Other reported symptoms include depression, insomnia, confusion, emotional liability, somnolence, and in rare cases, aseptic meningitis with fever and coma. Patients may also experience paresthesias, hallucinations, dream abnormalities, and pseudo-tumor cerebri.

Dermatologic reactions can range from common rashes, including maculopapular types and pruritis, to more severe conditions such as vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, and photoallergic skin reactions.

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

Hematologic reactions may include 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 can include decreased appetite, gynecomastia, hypoglycemic reactions, and acidosis.

Cardiovascular reactions may present 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 manifest 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 reactions reported include dry eyes and mouth, gingival ulcer, and rhinitis.

Postmarketing experience has revealed additional serious skin and appendage reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and fixed drug eruption.

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 monitor blood pressure in patients receiving both medications and consider dosage adjustments as necessary.

• Aspirin:

  • Ibuprofen can interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered shortly before aspirin. This interaction is noted with both immediate-release and enteric-coated low-dose aspirin. To mitigate this risk, it is advisable to administer immediate-release low-dose aspirin at least 2 hours prior to ibuprofen. However, this timing does not apply to enteric-coated formulations.

  • Due to the potential for increased cardiovascular events from this interaction, patients taking low-dose aspirin for cardioprotection who require analgesics should be considered for alternative NSAIDs that do not affect aspirin's antiplatelet effect or non-NSAID analgesics.

• 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.

• Warfarin-type Anticoagulants: While short-term studies have not shown significant effects of ibuprofen on prothrombin times in patients on coumarin-type anticoagulants, there is a risk of increased gastrointestinal bleeding when these medications are used together. Caution is advised when prescribing ibuprofen to patients on anticoagulants, and monitoring for signs of bleeding is recommended.

Pharmacokinetic Interactions

• 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 during concurrent administration. Patients should be monitored for signs of lithium toxicity 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.

• H-2 Antagonists: Co-administration of ibuprofen with 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 may be warranted 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 in the later stages of gestation. Administration of NSAIDs around 30 weeks of gestation or later can lead to premature closure of the fetal ductus arteriosus, a critical vessel in fetal circulation. Additionally, the use of NSAIDs from approximately 20 weeks of gestation onward has been linked to fetal renal dysfunction, which may result in oligohydramnios and, in some instances, neonatal renal impairment.

Due to these potential risks, it is recommended that the use of ibuprofen tablets be limited to the lowest effective dose and the shortest duration possible if necessary after 20 weeks of gestation. If treatment extends beyond 48 hours, monitoring with ultrasound for oligohydramnios is advised. Should oligohydramnios be detected, discontinuation of ibuprofen tablets should occur, followed by appropriate clinical follow-up.

There are no adequate, well-controlled studies in pregnant women, and the estimated background risk of major birth defects and miscarriage in the general population is 2-4% and 15-20%, respectively. While animal studies have not demonstrated developmental abnormalities, they have indicated that prostaglandins play a crucial role in fetal kidney development and implantation processes. In these studies, the use of prostaglandin synthesis inhibitors like ibuprofen has been associated with increased pre- and post-implantation loss and impaired kidney development at clinically relevant doses.

Published literature indicates that adverse outcomes, such as fetal renal dysfunction leading to oligohydramnios, may occur after days to weeks of NSAID treatment, although some cases of oligohydramnios have been reported as early as 48 hours post-initiation. While many instances of decreased amniotic fluid have been transient and reversible upon cessation of the drug, there are reports of irreversible neonatal renal dysfunction requiring invasive interventions.

Given the methodological limitations of existing postmarketing studies, including the absence of control groups and limited data on dosing and timing, the risk of adverse fetal and neonatal outcomes with maternal NSAID use remains uncertain. Therefore, ibuprofen tablets should only be used during pregnancy if the potential benefits outweigh the risks to the fetus.

Lactation

It is not known whether this drug is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants from ibuprofen tablets, lactating mothers should consider the importance of the drug to their health when making a decision to either discontinue nursing or discontinue the drug.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. In patients with reduced kidney function, renal prostaglandins play a compensatory role in maintaining renal perfusion; therefore, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation and, subsequently, renal blood flow. This can precipitate overt renal decompensation, particularly in patients at greatest risk, including those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.

Discontinuation of NSAID therapy typically results in recovery to the pretreatment state. However, there is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease, and treatment with ibuprofen tablets 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.

Additionally, the use of NSAIDs, including ibuprofen tablets, during pregnancy, particularly around 20 weeks gestation or later, may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes may occur after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after NSAID initiation. If NSAID treatment is required between 20 and 30 weeks of gestation, it is recommended to limit ibuprofen tablets to the lowest effective dose and shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if treatment extends beyond 48 hours, and ibuprofen tablets should be discontinued if oligohydramnios occurs, with follow-up according to clinical practice.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics and increased risk of adverse effects when treated with NSAIDs. Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury, particularly in individuals with compromised renal function. In patients with hepatic dysfunction, the administration of NSAIDs may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and precipitate renal decompensation.

Due to the potential for renal toxicity, treatment with ibuprofen tablets is not recommended for patients with advanced renal disease. If therapy with ibuprofen tablets is deemed necessary in patients with hepatic impairment, it is essential to initiate treatment with caution and to closely monitor renal function throughout the course of therapy. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of vigilant monitoring and assessment of liver and renal function in this patient population.

Overdosage

In cases of ibuprofen overdosage, clinical manifestations can vary significantly based on the amount ingested and the time elapsed since ingestion.

Clinical Presentation

A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg each). Approximately 1½ hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli. 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 exhibit periods of 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 responsive, able to sit independently and follow verbal commands. A blood level of ibuprofen measured 102.9 µg/mL approximately 8½ hours after ingestion, and the child appeared to have fully recovered by the 12-hour mark.

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 post-ingestion, which is approximately 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. After hospitalization, he received parenteral hydration and was placed on bed rest for three days, ultimately recovering without any reported sequelae.

Management Recommendations

In instances of acute ibuprofen overdosage, it is recommended to empty the stomach 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, administering alkali and inducing diuresis may be beneficial. Supportive measures are essential, and the use of oral activated charcoal can be considered to reduce both absorption and reabsorption of ibuprofen tablets.

Healthcare professionals should remain vigilant for potential symptoms and manage each case based on the clinical presentation and the specific circumstances surrounding the overdosage event.

Nonclinical Toxicology

In animal studies, no teratogenic effects were observed. However, adverse developmental outcomes were noted at doses that also resulted in maternal toxicity. Specifically, in rats, ibuprofen administration led to a decrease in fetal body weight and an increase in the incidence of skeletal malformations, which were associated with maternal toxicity.

Additionally, ibuprofen was shown to cause renal toxicity and gastrointestinal toxicity at high doses in nonclinical studies. These findings underscore the importance of considering both maternal and fetal health when evaluating the safety profile of ibuprofen in a developmental context.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include gastrointestinal bleeding, renal impairment, and hypersensitivity reactions. Notably, hypersensitivity reactions encompass cases of anaphylaxis and angioedema.

Patient Counseling

Patients should be advised to take ibuprofen with food or milk to minimize gastrointestinal irritation. It is important for patients to be informed about the potential for gastrointestinal bleeding, particularly if they have a history of ulcers or gastrointestinal bleeding. Healthcare providers should instruct patients to avoid alcohol while taking ibuprofen, as it may increase the risk of stomach bleeding.

Patients should be advised to consult their healthcare provider if they experience any signs of allergic reactions, such as rash, itching, or difficulty breathing. Additionally, patients should be informed that ibuprofen may cause dizziness or drowsiness, and they should exercise caution when driving or operating machinery.

It is essential for patients to keep ibuprofen out of reach of children and to seek medical attention immediately if a child accidentally ingests it. Patients should also be instructed to inform their healthcare provider if they are pregnant, plan to become pregnant, or are breastfeeding.

Healthcare providers should encourage patients to report any unusual weight gain, swelling, or changes in urine output. Furthermore, patients should be informed that prolonged use of ibuprofen may lead to kidney problems, and they should be monitored for signs of kidney dysfunction.

Storage and Handling

The product is supplied in well-closed containers to ensure integrity and stability. It should be stored at a temperature range of 20 ° to 25 °C (68 ° to 77 °F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the quality and efficacy of the product.

Additional Clinical Information

Physicians are advised to monitor patients for any signs or symptoms indicative of gastrointestinal (GI) bleeding. For patients undergoing long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that clinicians periodically check complete blood counts (CBC) and chemistry profiles to ensure patient safety.

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. Additionally, 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 TIME CAP LABORATORIES, INC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)