Ibuprofen

Description

Ibuprofen Oral Suspension, USP contains ibuprofen, USP as the active ingredient, which is classified as a member of the propionic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen, USP is a racemic mixture of +S- and -R-enantiomers, appearing as a white to off-white crystalline powder with a melting point of 74° to 77°C. It is characterized by its low solubility in water (less than 0.1 mg/mL) but demonstrates good solubility in organic solvents such as ethanol and acetone. The compound has a pKa of 4.43 ± 0.03 and an n-octanol/water partition coefficient of 11.7 at pH 7.4. The chemical name for ibuprofen, USP is (±)-2-(p-Isobutylphenyl) propionic acid, with a molecular weight of 206.28 and a molecular formula of C13H18O2.

Ibuprofen Oral Suspension, USP is formulated as a sucrose-sweetened, orange-colored, berry-flavored suspension, containing 100 mg of ibuprofen, USP per 5 mL (20 mg/mL). The formulation includes inactive ingredients such as acesulfame potassium, citric acid anhydrous, D&C yellow #10, FD&C red #40, glycerin, polysorbate 80, pregelatinized corn starch, purified water, sodium benzoate, strawberry flavor, sucrose, and xanthan gum.

Uses and Indications

Ibuprofen Oral Suspension is indicated for use in pediatric patients and adults for the management of various conditions.

In pediatric patients aged 6 months to 2 years, Ibuprofen Oral Suspension is indicated for the reduction of fever, relief of mild to moderate pain, and alleviation of signs and symptoms associated with juvenile arthritis.

In adults, this formulation is indicated for the treatment of primary dysmenorrhea and for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis.

There are no teratogenic or nonteratogenic effects associated with the use of Ibuprofen Oral Suspension.

Dosage and Administration

Pediatric patients requiring fever reduction should receive a recommended dose of 5 mg/kg if the baseline temperature is less than 102.5ºF, and 10 mg/kg if the baseline temperature is 102.5ºF or greater. The duration of fever reduction typically lasts for 6 to 8 hours. The maximum daily dose for pediatric patients is 40 mg/kg.

For analgesia in pediatric patients, the recommended dosage is 10 mg/kg administered every 6 to 8 hours, with a maximum daily dose also set at 40 mg/kg. In cases of juvenile arthritis, the recommended dose ranges from 30 to 40 mg/kg/day, divided into three to four doses. Patients with milder disease may be treated with a lower dose of 20 mg/kg/day. Doses exceeding 50 mg/kg/day are not recommended.

In adult patients, the dosage for primary dysmenorrhea is 400 mg every 4 hours as necessary for pain relief. For rheumatoid arthritis and osteoarthritis, the suggested daily dosage ranges from 1200 to 3200 mg, which 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 individualize the dosage for each patient, adjusting based on symptom severity and response to treatment.

Contraindications

Ibuprofen Oral Suspension is contraindicated in patients with known hypersensitivity to ibuprofen. It should not be administered to individuals who have experienced asthma, urticaria, or allergic-type reactions following the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as severe, potentially fatal, anaphylactic-like reactions have been reported in these patients. Additionally, the use of ibuprofen 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

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen oral suspension, are associated with significant risks that healthcare professionals must consider when prescribing and monitoring treatment.

Cardiovascular Risks NSAIDs are linked to 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 known to escalate with prolonged use. Clinical trials indicate that the risk of these events is particularly pronounced at higher doses. Patients with existing cardiovascular disease or risk factors are at a heightened risk for these serious events.

Gastrointestinal Adverse Events The use of NSAIDs can lead to severe gastrointestinal complications, including bleeding, ulceration, and perforation of the stomach or intestines, which may occur without warning and can be fatal. Elderly patients are especially vulnerable to these gastrointestinal risks. Physicians should monitor patients on long-term NSAID therapy for signs or symptoms of gastrointestinal bleeding and consider periodic checks of hemoglobin or hematocrit in those exhibiting any signs of anemia.

Hypertension NSAIDs, including ibuprofen, may cause new-onset hypertension or exacerbate pre-existing hypertension. Regular monitoring of blood pressure is advised for patients receiving long-term NSAID treatment.

Dermatological Reactions Serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported with NSAID use and can be fatal. Patients should be advised to discontinue ibuprofen oral suspension at the first sign of a skin rash or any other hypersensitivity reaction.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) DRESS has been reported in patients taking NSAIDs, including ibuprofen oral suspension, with some cases being fatal or life-threatening. Immediate evaluation and discontinuation of the drug are warranted if symptoms consistent with DRESS arise.

Pregnancy Considerations The use of NSAIDs, including ibuprofen oral suspension, is contraindicated in pregnant women at approximately 30 weeks of gestation and later due to the risk of premature closure of the fetal ductus arteriosus.

Corticosteroid Considerations Ibuprofen is not a substitute for corticosteroids and should not be used to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids can 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.

Laboratory Monitoring For patients on long-term NSAID therapy, periodic monitoring of a complete blood count (CBC) and chemistry profile is recommended. If clinical signs or symptoms indicative of liver or renal disease develop, or if liver function tests show persistent or worsening abnormalities, ibuprofen should be discontinued.

Emergency and Discontinuation Instructions Patients should be instructed to seek emergency medical assistance if they experience an anaphylactoid reaction. They should also be informed about the signs and symptoms of serious cardiovascular events and the appropriate actions to take if these occur. Immediate discontinuation of ibuprofen oral suspension is advised at the first appearance of a skin rash or any other sign of hypersensitivity, and patients should be evaluated promptly if symptoms of DRESS are present.

Side Effects

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

Common adverse reactions, occurring in 1 to 10% of patients, include abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, fluid retention, and various gastrointestinal symptoms such as abdominal pain, bloating, constipation, diarrhea, dyspepsia, epigastric pain, flatulence, heartburn, nausea, and vomiting. Additional common reactions include headaches, increased bleeding time, nervousness, pruritus, rashes (including maculopapular), and tinnitus.

Occasionally reported adverse reactions encompass a broader spectrum of effects. Systemic reactions may include fever, infection, and sepsis. Cardiovascular effects can manifest as congestive heart failure in patients with marginal cardiac function, hypertension, tachycardia, and syncope. Digestive system reactions may involve dry mouth, duodenitis, esophagitis, gastric or duodenal ulcers with bleeding and/or perforation, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice, melena, and rectal bleeding. Hematologic reactions include ecchymosis, eosinophilia, leukopenia, purpura, stomatitis, and thrombocytopenia. Metabolic and nutritional changes may present as weight fluctuations.

Nervous system effects can include anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, paresthesia, somnolence, tremors, and vertigo. Respiratory reactions may consist of asthma and dyspnea. Skin and appendage reactions can include alopecia, photosensitivity, and increased sweating. Visual disturbances such as blurred vision have also been reported. Urogenital effects may involve cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, and acute renal failure in patients with pre-existing significantly impaired renal function.

Rare adverse reactions have also been documented. Systemic reactions may include anaphylactic and anaphylactoid reactions, as well as appetite changes. Cardiovascular issues can involve arrhythmia, cerebrovascular accidents, hypotension, myocardial infarction, palpitations, and vasculitis. Digestive system reactions may include eructation, gingival ulcers, hepatorenal syndrome, liver necrosis, liver failure, and pancreatitis. Hematologic reactions can be severe, including agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, neutropenia, and pancytopenia. Metabolic reactions may present as hyperglycemia.

Nervous system effects can be serious, including convulsions, coma, emotional lability, hallucinations, and aseptic meningitis. Respiratory reactions may include apnea, respiratory depression, pneumonia, and rhinitis. Skin and appendage reactions can be severe, including angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, fixed drug eruptions, urticaria, and vesiculobullous eruptions. Special senses may be affected, leading to amblyopia, conjunctivitis, dry eyes, and hearing impairment. Urogenital reactions may include azotemia, decreased creatinine clearance, glomerulitis, renal papillary necrosis, and tubular necrosis.

It is important to note the warnings associated with this medication. There is an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may arise early in treatment and may increase with prolonged use. Additionally, there is an increased risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can also be fatal. These gastrointestinal events can occur at any time during treatment and without warning symptoms, with elderly patients being at greater risk for such serious events.

Drug Interactions

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and other medications may lead to significant drug interactions that require careful consideration and monitoring.

Antihypertensive Agents NSAIDs may diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors. Clinicians should monitor blood pressure in patients receiving both NSAIDs and ACE inhibitors to ensure therapeutic efficacy.

Antiplatelet Agents Pharmacodynamic studies indicate that ibuprofen can interfere with the antiplatelet activity of aspirin, particularly when ibuprofen is administered prior to enteric-coated low-dose aspirin. This interaction persists even with a once-daily regimen of ibuprofen at 400 mg. To mitigate this risk, it is advisable to administer immediate-release low-dose aspirin at least 2 hours before ibuprofen. However, this timing does not apply to enteric-coated formulations. Given the potential for increased cardiovascular events due to this interaction, alternative analgesics that do not affect aspirin's antiplatelet effect should be considered for patients using low-dose aspirin for cardioprotection.

Diuretics Clinical studies and post-marketing observations have shown that ibuprofen may reduce the natriuretic effect of furosemide and thiazide diuretics, likely due to inhibition of renal prostaglandin synthesis. Patients receiving concomitant therapy with NSAIDs should be closely monitored for signs of renal failure and to ensure the efficacy of diuretics.

Lithium Ibuprofen has been shown to elevate plasma lithium levels and decrease renal clearance of lithium, with a mean increase in minimum lithium concentration of 15% and a 19% reduction in renal clearance during concurrent administration. Careful observation for signs of lithium toxicity is recommended when these drugs are used together.

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

Anticoagulants While several short-term studies have not demonstrated a significant effect of ibuprofen on prothrombin times or other clotting factors in patients on warfarin-type anticoagulants, there is a documented risk of bleeding when these medications are used together. The synergistic effects of warfarin and NSAIDs on gastrointestinal bleeding necessitate caution in prescribing ibuprofen to patients on anticoagulants, as the risk of serious GI bleeding is elevated in this population.

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 in pediatric patients below the age of 6 months have not been established. For children aged 6 months and older, dosing should be guided by body weight to ensure appropriate administration.

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 NSAIDs, including ibuprofen oral suspension, during pregnancy is associated with significant risks, particularly when administered around 20 weeks of gestation or later. The use of these medications can lead to premature closure of the fetal ductus arteriosus and fetal renal dysfunction, which may result in oligohydramnios and, in some cases, neonatal renal impairment. Therefore, it is recommended to limit the dose and duration of ibuprofen oral suspension use between approximately 20 and 30 weeks of gestation, and to avoid its use at around 30 weeks of gestation and later in pregnancy.

Observational studies regarding the potential risks of NSAID use during the first and second trimesters have yielded inconclusive results. Animal reproductive studies have not demonstrated developmental abnormalities; however, these studies may not accurately predict human responses. Prostaglandins play a crucial role in various reproductive processes, and their inhibition by NSAIDs like ibuprofen has been associated with increased pre- and post-implantation loss in animal models. Additionally, prostaglandins are vital for fetal kidney development, and the use of prostaglandin synthesis inhibitors has been reported to impair kidney development at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2 to 4% and 15 to 20%, respectively. There are no adequate, well-controlled studies in pregnant women, and ibuprofen should only be used during pregnancy if the potential benefits outweigh the risks to the fetus.

If NSAID use is deemed necessary after 20 weeks of gestation, it is crucial to limit the use to the lowest effective dose for the shortest duration possible. If treatment with ibuprofen oral suspension extends beyond 48 hours, monitoring with ultrasound for oligohydramnios is advised. Should oligohydramnios occur, discontinuation of ibuprofen oral suspension is recommended, followed by appropriate clinical follow-up.

Published literature indicates that maternal NSAID use at around 30 weeks of gestation or later may lead to premature closure of the fetal ductus arteriosus. Reports also describe associations between maternal NSAID use after 20 weeks of gestation and fetal renal dysfunction, which can manifest as oligohydramnios or neonatal renal impairment. These adverse outcomes typically arise after days to weeks of treatment, although oligohydramnios has been reported as early as 48 hours after initiation. While many cases of decreased amniotic fluid were transient and reversible upon cessation of the drug, some instances of neonatal renal dysfunction occurred without oligohydramnios and required invasive interventions.

It is important to note that methodological limitations in postmarketing studies, such as the absence of control groups and limited data on dosage and duration of exposure, hinder the establishment of a reliable risk estimate for adverse fetal and neonatal outcomes associated with maternal NSAID use. Furthermore, the safety data primarily involve preterm infants, raising uncertainties about the generalizability of reported risks to full-term infants exposed to NSAIDs through maternal use.

Lactation

It is not known whether this drug is excreted in human milk. Given that many drugs are excreted in human milk and considering the potential for serious adverse reactions in nursing infants from ibuprofen, lactating mothers should make a decision regarding the continuation of breastfeeding or the discontinuation of the drug. This decision should take into account the importance of the drug to the mother.

Renal Impairment

Long-term administration of nonsteroidal anti-inflammatory drugs (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. In these individuals, the use of NSAIDs can lead to a dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow, potentially precipitating overt renal decompensation.

Patients at the highest risk for these adverse effects include 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.

There is no available information from controlled clinical studies regarding the use of ibuprofen in patients with advanced renal disease; therefore, treatment with ibuprofen is not recommended in this population. If ibuprofen therapy is deemed necessary, close monitoring of the patient’s renal function is advised.

Additionally, the use of NSAIDs, including ibuprofen oral suspension, 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 can manifest after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after initiation of NSAID therapy. While oligohydramnios is often reversible upon discontinuation of treatment, if NSAID use is required between 20 and 30 weeks gestation, it is recommended to limit ibuprofen oral suspension 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 oral suspension 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 nonsteroidal anti-inflammatory drugs (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 compensatory role in maintaining renal perfusion. In patients with compromised liver function, the administration of an NSAID may lead to a dose-dependent reduction in prostaglandin formation, which can subsequently decrease renal blood flow and potentially precipitate overt renal decompensation.

Patients at the highest risk for these adverse reactions include those with impaired renal function, heart failure, liver dysfunction, individuals taking diuretics and ACE inhibitors, and the elderly. Therefore, it is crucial to exercise caution when considering NSAID therapy in this population.

Currently, there is no available information from controlled clinical studies regarding the use of ibuprofen in patients with advanced renal disease. Consequently, treatment with ibuprofen is not recommended for these patients. If ibuprofen therapy is deemed necessary, close monitoring of the patient's renal function is advised to mitigate potential risks. Discontinuation of NSAID therapy typically results in recovery to the pretreatment state, underscoring the importance of careful patient management in those with hepatic impairment.

Overdosage

The toxicity associated with ibuprofen overdose is influenced by the quantity ingested and the time elapsed since ingestion; however, individual responses may vary, necessitating a case-by-case evaluation. Although serious toxicity and fatalities are rare, they have been documented in the medical literature.

Symptoms of Overdosage

The most commonly reported symptoms following ibuprofen overdose include abdominal pain, nausea, vomiting, lethargy, and drowsiness. Additional central nervous system manifestations may include headache, tinnitus, CNS depression, and seizures. In rare instances, more severe complications such as metabolic acidosis, coma, acute renal failure, and apnea—particularly in very young children—may occur. Cardiovascular effects, including hypotension, bradycardia, tachycardia, and atrial fibrillation, have also been noted.

Management of Overdosage

The management of acute ibuprofen overdose is primarily supportive. It may be necessary to address hypotension, acidosis, and gastrointestinal bleeding as part of the treatment protocol. In cases of acute overdose, gastric emptying should be performed, ideally through ipecac-induced emesis or gastric lavage. Emesis is most effective when initiated within 30 minutes of ingestion.

Orally administered activated charcoal may be beneficial in reducing both the absorption and reabsorption of ibuprofen. In pediatric patients, the estimated amount of ibuprofen ingested per body weight can assist in predicting the potential for toxicity, although each case must be evaluated individually.

For children, ingestion of less than 100 mg/kg is generally considered unlikely to result in toxicity. Those ingesting between 100 to 200 mg/kg may be managed with induced emesis and should be observed for a minimum of four hours. Children who ingest between 200 to 400 mg/kg require immediate gastric emptying and at least four hours of observation in a healthcare facility. In cases where ingestion exceeds 400 mg/kg, immediate medical referral, careful observation, and appropriate supportive therapy are essential. Ipecac-induced emesis is contraindicated in these higher doses due to the risk of convulsions and aspiration of gastric contents.

In adult patients, the reported dose ingested does not reliably predict the likelihood of toxicity. Therefore, the need for referral and follow-up should be determined based on the specific circumstances surrounding the overdose. Symptomatic adults should undergo careful evaluation, observation, and supportive care as needed.

Nonclinical Toxicology

Teratogenic effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen oral suspension, have been observed, particularly in pregnant women around 30 weeks gestation and later. The use of NSAIDs during this period increases the risk of premature closure of the fetal ductus arteriosus. Additionally, administration of NSAIDs, including ibuprofen oral suspension, at approximately 20 weeks gestation or later may lead to fetal renal dysfunction, resulting in oligohydramnios and, in some instances, neonatal renal impairment. These adverse effects can 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 lead to complications such as limb contractures and delayed lung maturation. In certain post-marketing cases of impaired neonatal renal function, invasive interventions like exchange transfusion or dialysis were necessary.

In situations where NSAID treatment is deemed necessary between 20 and 30 weeks of gestation, it is recommended to limit the use of ibuprofen oral suspension to the lowest effective dose for the shortest duration possible. Ultrasound monitoring of amniotic fluid should be considered if treatment extends beyond 48 hours, and ibuprofen oral suspension should be discontinued if oligohydramnios occurs, with appropriate follow-up according to clinical practice.

Data from observational studies regarding potential embryo-fetal risks of NSAID use during the first or second trimesters of pregnancy remain inconclusive. Animal reproductive studies conducted in rats and rabbits have not shown evidence of developmental abnormalities; however, these studies may not accurately predict human responses. Prostaglandins play a critical role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, the administration of prostaglandin synthesis inhibitors, such as ibuprofen, has been associated with increased pre- and post-implantation loss. Furthermore, prostaglandins are essential for fetal kidney development, and published animal studies indicate that prostaglandin synthesis inhibitors can impair kidney development when administered at clinically relevant doses.

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

In animal studies, the administration of prostaglandin synthesis inhibitors, including ibuprofen, has resulted in increased pre- and post-implantation loss. Prostaglandins are crucial for fetal kidney development, and evidence from published animal studies suggests that prostaglandin synthesis inhibitors can adversely affect kidney development when given at clinically relevant doses.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of ibuprofen oral suspension. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients, with some cases being fatal or life-threatening. DRESS typically presents with symptoms such as fever, rash, lymphadenopathy, and/or facial swelling, and may also involve other clinical manifestations including hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Eosinophilia is often present, and early signs of hypersensitivity may occur even in the absence of a rash. Immediate discontinuation of ibuprofen oral suspension and patient evaluation are recommended upon the appearance of such symptoms.

Anaphylactoid reactions have been observed in patients without prior exposure to ibuprofen. It is contraindicated in patients with the aspirin triad, a symptom complex that typically affects asthmatic individuals who may experience severe bronchospasm after taking aspirin or other NSAIDs.

Serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, sometimes occurring without warning. Patients should be educated on the signs and symptoms of serious skin reactions, and ibuprofen should be discontinued at the first indication of a rash or other hypersensitivity signs.

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

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, with a notable incidence of death in the first year post-MI being 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in those not exposed to NSAIDs.

The use of NSAIDs, including ibuprofen oral suspension, during pregnancy, particularly at around 20 weeks gestation or later, has been linked to fetal renal dysfunction leading to oligohydramnios, with some cases of neonatal renal impairment reported. These adverse outcomes typically arise after days to weeks of treatment, although oligohydramnios has been infrequently reported as early as 48 hours after initiation. In some instances of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were necessary.

A limited number of case reports have documented maternal NSAID use resulting in neonatal renal dysfunction without oligohydramnios, with some cases being irreversible and requiring invasive interventions.

Patient Counseling

Patients should be advised to remain vigilant for symptoms indicative of cardiovascular thrombotic events, such as chest pain, shortness of breath, weakness, or slurring of speech. They should be instructed to report any of these symptoms to their healthcare provider immediately.

It is important to inform patients that ibuprofen, like other nonsteroidal anti-inflammatory drugs (NSAIDs), may cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, including ulcers and bleeding, which could lead to hospitalization or even death. Patients should be alert for signs and symptoms of ulcerations and bleeding, such as epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical advice if they observe any of these indicative signs.

Patients should be counseled to discontinue ibuprofen oral suspension immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

Additionally, 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 essential to inform patients 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 symptoms occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should also be informed of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. In the event of these symptoms, patients should be advised to seek immediate emergency help.

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

Storage and Handling

The product is supplied in a tight container as defined by the United States Pharmacopeia (USP). It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Prior to use, it is essential to shake the container well to ensure proper mixing of the contents.

Additional Clinical Information

Clinicians are advised to monitor patients for signs or symptoms of gastrointestinal (GI) bleeding during treatment. For patients undergoing long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), it is recommended that complete blood counts (CBC) and chemistry profiles be assessed periodically to ensure safety and efficacy.

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 should be discontinued. Additionally, if abnormal liver function 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 Actavis Pharma, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)