Alivio

Description

Each tablet contains 400 mg of Ibuprofen, USP. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used for its analgesic and anti-inflammatory properties. The formulation is designed for oral administration.

Uses and Indications

Ibuprofen tablets are indicated for the relief of the signs and symptoms associated with rheumatoid arthritis and osteoarthritis. Additionally, these tablets are indicated for the relief of mild to moderate pain and for the treatment of primary dysmenorrhea.

Controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in pediatric populations have not been conducted. Therefore, caution is advised when considering the use of this medication in children.

Dosage and Administration

Healthcare professionals are advised to refer to the package insert for complete product information regarding dosage and administration. Specific details concerning the route, method, and frequency of administration are not provided in the available data. It is essential to consult the package insert to ensure proper use and adherence to recommended guidelines.

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). Furthermore, ibuprofen tablets are contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

Cardiovascular effects associated with NSAID use include an increased risk of serious thrombotic events, myocardial infarction, and stroke, which may be fatal. This risk is heightened with prolonged use, particularly in patients with pre-existing cardiovascular disease or risk factors. Ibuprofen is contraindicated for the treatment of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

NSAIDs may also lead to the onset of new hypertension or exacerbate existing hypertension, potentially increasing the incidence of cardiovascular events. Therefore, it is essential to monitor blood pressure closely during NSAID therapy.

Patients with a history of congestive heart failure or fluid retention should use NSAIDs with caution, as these medications can cause fluid retention and edema.

Gastrointestinal adverse events, including inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, can occur with NSAID use and may be fatal. These events can arise unexpectedly, with or without warning symptoms. Patients with a prior history of peptic ulcer disease or gastrointestinal bleeding are at significantly increased risk, with a greater than tenfold increase in the likelihood of developing a GI bleed compared to those without such risk factors.

Long-term use of NSAIDs has been associated with renal complications, including renal papillary necrosis and other forms of renal injury. Patients at higher risk include those with impaired renal function, heart failure, liver dysfunction, those on diuretics or ACE inhibitors, and the elderly. Close monitoring of renal function is recommended for patients with advanced renal disease who require ibuprofen therapy.

Anaphylactoid reactions may occur in individuals without prior exposure to ibuprofen, necessitating immediate emergency medical assistance in such cases. Additionally, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), can develop without warning. Patients should discontinue NSAID use at the first sign of a skin rash or any indication of hypersensitivity.

In late pregnancy, ibuprofen should be avoided due to the risk of premature closure of the ductus arteriosus.

Healthcare professionals and patients should remain vigilant for signs and symptoms indicative of serious cardiovascular events and gastrointestinal complications during NSAID therapy. Blood pressure should be monitored closely during the initiation and throughout the course of NSAID treatment. If any serious gastrointestinal event is suspected, prompt evaluation and treatment should be initiated. Discontinuation of NSAID therapy is advised at the first appearance of a skin rash or any other sign of hypersensitivity, and emergency medical help should be sought in cases of anaphylactoid reactions.

Side Effects

The most frequent adverse reactions associated with ibuprofen tablets are gastrointestinal in nature, with clinical trials indicating that the percentage of patients reporting one or more gastrointestinal complaints ranges from 4% to 16%. Notably, the incidence of gastrointestinal side effects is higher at doses of 3200 mg/day compared to doses of 2400 mg or less in patients with rheumatoid arthritis.

Serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, can occur at any time during treatment and without warning symptoms. Elderly patients are particularly at increased risk for these serious gastrointestinal events. In clinical studies, upper gastrointestinal ulcers, gross bleeding, or perforation due to NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year.

Ibuprofen tablets are also associated with an increased risk of serious 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. Consequently, ibuprofen is contraindicated for the treatment of peri-operative pain in the context of coronary artery bypass graft (CABG) surgery.

Long-term administration of NSAIDs, including ibuprofen, has been linked to renal toxicity, including renal papillary necrosis and other forms of renal injury. This is particularly relevant for patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion.

Anaphylactoid reactions may occur in patients without prior exposure to ibuprofen tablets, and the medication should not be administered to individuals with the aspirin triad. Serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have also been reported and can be fatal, occurring without warning.

Additional adverse reactions may include borderline elevations in liver tests, observed in up to 15% of patients taking NSAIDs, including ibuprofen. Rare but severe hepatic reactions, such as jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some of which have resulted in fatal outcomes, have been documented. Anemia may occur in patients receiving ibuprofen, potentially due to fluid retention, occult or gross gastrointestinal blood loss, or an unclear effect on erythropoiesis.

Visual disturbances, including blurred or diminished vision, scotomata, and changes in color vision, have been reported. If such symptoms develop, discontinuation of ibuprofen is advised. Additionally, rare cases of aseptic meningitis with fever and coma have been observed in patients undergoing ibuprofen therapy.

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 may 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 ensuring diuretic efficacy is advised during concurrent NSAID therapy.

• Warfarin-Type Anticoagulants: While short-term studies have not shown significant effects of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, there is an increased risk of gastrointestinal bleeding when NSAIDs are used alongside anticoagulants. Caution is warranted due to the synergistic effects on GI bleeding.

Pharmacokinetic Interactions

• Aspirin: The co-administration of ibuprofen with aspirin may reduce the protein binding of aspirin, although it does not alter the clearance of free ibuprofen. Due to the potential for increased adverse effects, concomitant use of ibuprofen and aspirin is generally not recommended.

• 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. Careful monitoring for signs of lithium toxicity is recommended when these medications are used together.

• Methotrexate: NSAIDs may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is advised when administering NSAIDs in conjunction with methotrexate.

H-2 Antagonists: Studies indicate that the co-administration of cimetidine or ranitidine with ibuprofen does not significantly affect ibuprofen serum concentrations. Therefore, no dosage adjustments are necessary when these medications are used together.

Healthcare providers should remain vigilant for potential interactions and consider appropriate monitoring or dosage adjustments as necessary when prescribing ibuprofen alongside these medications.

Packaging & NDC

The table below lists all NDC Code configurations of Alivio (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 and adolescents.

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.

Pregnancy

Pregnancy Category C. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities; however, 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. Additionally, the effects of ibuprofen tablets on labor and delivery in pregnant women are unknown. In rat studies involving NSAIDs, there was an increased incidence of dystocia, delayed parturition, and decreased pup survival. Healthcare professionals should carefully consider these factors when 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 nursing or discontinue the drug.

Renal Impairment

Long-term administration of NSAIDs has been associated with renal papillary necrosis and other forms of renal injury. Renal toxicity may occur in patients where renal prostaglandins play a compensatory role in maintaining renal perfusion. The administration of an NSAID can lead to a dose-dependent reduction in prostaglandin formation, which may subsequently decrease renal blood flow and precipitate overt renal decomposition.

Patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly are at the greatest risk for renal reactions. In cases where NSAID therapy is discontinued, recovery to the pretreatment state is typically observed.

There is no available information from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease, and treatment with ibuprofen tablets is not recommended for these patients. If initiation of ibuprofen tablet therapy is deemed necessary in patients with advanced renal disease, close monitoring of renal function is advised.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no established 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 patient's age and weight.

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 1.5 hours post-ingestion, the child presented to the emergency department in an apneic and cyanotic state, responding only to painful stimuli, which was sufficient to induce respiration. Upon examination, a greenish-yellow fluid was aspirated from the stomach, revealing no evidence of ibuprofen.

Two hours after ingestion, the child's condition stabilized, although she continued to respond solely to painful stimuli and experienced intermittent apnea lasting 5 to 10 seconds. The child was subsequently admitted to intensive care, where sodium bicarbonate, along with dextrose and normal saline infusions, 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 8.5 hours after ingestion, and by 12 hours, the child appeared to have fully recovered.

In two additional cases involving children weighing approximately 10 kg who ingested about 120 mg/kg of ibuprofen, no acute intoxication or late sequelae were observed. One child exhibited a blood level of 700 µg/mL 90 minutes after ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

Management of Overdosage

For acute ibuprofen overdosage, it is recommended to empty the stomach through vomiting or gastric lavage; however, it is important to note that minimal drug recovery is expected if more than one hour has passed since ingestion. Supportive measures should be prioritized, and the administration of oral activated charcoal may be beneficial in reducing both absorption and reabsorption of ibuprofen.

Given the acidic nature of ibuprofen and its urinary excretion, administering alkali and inducing diuresis may theoretically enhance elimination.

Severe Cases

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

Healthcare professionals should remain vigilant in monitoring patients for potential symptoms of overdosage and implement appropriate management strategies to ensure optimal recovery.

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 observed compared to previous reports. Specifically, a decrease in hemoglobin of 1 gram or more occurred in 17.1% of 193 patients receiving 1600 mg of ibuprofen daily for osteoarthritis and in 22.8% of 189 patients taking 2400 mg of ibuprofen daily for rheumatoid arthritis. Additionally, positive stool occult blood tests and elevated serum creatinine levels were noted in these studies. Furthermore, reported side effects were more frequent at doses of 3200 mg per day than at doses of 2400 mg or less per day in clinical trials involving patients with rheumatoid arthritis.

Patient Counseling

Patients should be informed of essential information before initiating therapy with ibuprofen tablets, as well as periodically during the course of ongoing therapy. Healthcare providers should encourage patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Patients should be made aware that ibuprofen, like other NSAIDs, may cause serious cardiovascular (CV) side effects, including myocardial infarction (MI) or stroke, which could lead to hospitalization or even death. Although serious CV events can occur without warning symptoms, patients should be vigilant for signs and symptoms such as chest pain, shortness of breath, weakness, or slurring of speech. They should be advised to seek medical advice if they observe any of these indicative signs or symptoms and understand the importance of follow-up.

Additionally, patients should be informed that ibuprofen can cause gastrointestinal (GI) discomfort and, in rare cases, serious GI side effects such as ulcers and bleeding, which may also result in hospitalization or death. Serious GI tract ulcerations and bleeding can occur without warning symptoms; therefore, patients should be alert 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 to recognize the importance of follow-up.

Patients should also be made aware that ibuprofen 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 vigilant 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. Furthermore, they should 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 occur, patients should be instructed to stop therapy and seek immediate medical attention.

Patients should also be educated on 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, patients should be advised that ibuprofen tablets should be avoided in late pregnancy, as with other NSAIDs, due to the risk of premature closure of the ductus arteriosus.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product at a temperature range of 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions must be maintained to ensure the integrity and efficacy of the product.

Additional Clinical Information

Physicians should monitor patients on long-term NSAID treatment for signs or symptoms of gastrointestinal (GI) bleeding and periodically check complete blood count (CBC) and chemistry profiles. If patients exhibit clinical signs consistent with liver or renal disease, systemic manifestations (e.g., eosinophilia, rash), or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued.

Before initiating therapy with ibuprofen, patients should be counseled on potential serious cardiovascular side effects, including myocardial infarction (MI) and stroke, and advised to recognize symptoms such as chest pain and shortness of breath. They should also be informed about the risk of GI discomfort and serious complications like ulcers and bleeding, with instructions to report symptoms such as epigastric pain or melena. Additionally, patients should be aware of serious skin reactions, signs of hepatotoxicity, and anaphylactoid reactions, and should seek immediate medical attention if these occur. In late pregnancy, ibuprofen should be avoided due to the risk of premature closure of the ductus arteriosus.

FDA Insert (PDF)

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

View full prescribing information (PDF)