Alivio

Description

Each tablet contains 600 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 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 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 in 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. It is important to note that ibuprofen tablets are 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, blood pressure should be monitored closely during NSAID therapy.

Gastrointestinal adverse events are a significant concern with NSAID use, as they can result in serious complications such as inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, which can be fatal. These events may occur unexpectedly, with or without warning symptoms. Patients with a history of peptic ulcer disease or gastrointestinal bleeding are at more than a tenfold increased risk for developing gastrointestinal bleeding compared to those without such risk factors. Both patients and healthcare providers should remain vigilant for signs and symptoms of gastrointestinal ulcerations and bleeding during NSAID therapy, initiating further evaluation and treatment promptly if a serious event is suspected.

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

Anaphylactoid reactions can occur in patients without prior exposure to ibuprofen, necessitating immediate emergency medical assistance if such a reaction occurs. Additionally, NSAIDs may cause serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. The use of ibuprofen should be discontinued 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. Patients should be educated on the signs and symptoms of serious cardiovascular events and the appropriate actions to take if they occur.

Monitoring parameters include regular blood pressure checks throughout NSAID treatment and close observation of renal function in patients with advanced renal disease. Emergency medical help should be sought in cases of anaphylactoid reactions, and the drug should be stopped immediately if any skin rash or hypersensitivity signs appear.

Side Effects

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

Serious adverse reactions include an increased risk of cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may escalate with prolonged use, particularly in patients with existing cardiovascular disease or risk factors. All NSAIDs, including ibuprofen, share this potential risk.

Gastrointestinal risks are significant, as NSAIDs can lead to serious adverse events such as bleeding, ulceration, and perforation of the stomach or intestines, which may also be fatal. These events can occur unexpectedly and without warning symptoms. In clinical studies, upper gastrointestinal ulcers, gross bleeding, or perforation occurred in approximately 1% of patients treated for 3-6 months and in about 2-4% of those treated for one year. Elderly patients are particularly vulnerable to these serious gastrointestinal events.

Long-term use of NSAIDs has been associated with renal complications, including renal papillary necrosis and other forms of renal injury. Patients with pre-existing renal impairment, heart failure, liver dysfunction, those on diuretics or ACE inhibitors, and the elderly are at an increased risk for renal toxicity.

Anaphylactoid reactions may occur in patients who have not previously been exposed to ibuprofen tablets, and the medication should be avoided in 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, often occurring without prior warning.

Hepatic effects may manifest as borderline elevations in liver tests 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 death, have been documented.

Hematological effects, including anemia, may occur in patients receiving NSAIDs, potentially due to fluid retention, occult or gross gastrointestinal blood loss, or an unclear impact on erythropoiesis. Additionally, ophthalmological effects such as blurred or diminished vision, scotomata, and changes in color vision have been reported.

Aseptic meningitis, characterized by fever and coma, has been observed on rare occasions in patients undergoing ibuprofen therapy. Patients should be informed of the signs and symptoms associated with serious cardiovascular events, gastrointestinal ulcerations and bleeding, serious skin reactions, hepatotoxicity, and anaphylactoid reactions.

Drug Interactions

Concomitant use of ibuprofen with certain drug classes may lead to significant interactions that warrant careful consideration and monitoring.

ACE Inhibitors Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may diminish the antihypertensive effect of ACE inhibitors. This interaction should be considered in patients receiving both medications.

Aspirin The co-administration of ibuprofen with aspirin may reduce the protein binding of ibuprofen; however, the clearance of free ibuprofen remains unchanged. The clinical significance of this interaction is not well established, but it is generally advised to avoid concomitant use due to the potential for increased adverse effects.

Diuretics Ibuprofen has been shown to reduce the natriuretic effect of diuretics such as furosemide and thiazides in some patients, likely due to the inhibition of renal prostaglandin synthesis. Patients receiving both ibuprofen and diuretics should be closely monitored for signs of renal failure and to ensure the efficacy of the diuretic therapy.

Lithium Ibuprofen can elevate plasma lithium levels and decrease renal clearance of lithium, as evidenced by a study showing a 15% increase in mean minimum lithium concentration 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, including ibuprofen, may competitively inhibit the accumulation of methotrexate, potentially enhancing its toxicity. Caution is advised when administering ibuprofen alongside methotrexate.

Warfarin-type Anticoagulants While short-term studies have not demonstrated a significant effect of ibuprofen on prothrombin times or clotting factors in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of ibuprofen and anticoagulants may lead to a synergistic effect on gastrointestinal bleeding, necessitating caution in concurrent use.

H2 Antagonists Co-administration of ibuprofen with H2 antagonists such as cimetidine or ranitidine has not shown any significant impact on ibuprofen serum concentrations in studies involving human volunteers.

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 (65 years and older) with this medication, as with any nonsteroidal anti-inflammatory drugs (NSAIDs). It is important for healthcare providers to closely monitor this population for potential adverse effects and to consider appropriate dosage adjustments based on individual patient needs and responses.

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 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 presentation can vary significantly based on the amount ingested and the timing of medical intervention.

Clinical Presentation and Symptoms A notable case involved a 19-month-old child who ingested between 7 to 10 ibuprofen tablets (400 mg). Approximately 1.5 hours post-ingestion, the child presented to the emergency department 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.

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 post-ingestion, which is approximately ten times the peak levels noted in absorption-excretion studies.

Management of Overdosage For adults, a case was reported involving a 19-year-old male who ingested 8,000 mg of ibuprofen over several hours. He experienced dizziness and exhibited nystagmus. Following hospitalization, he received parenteral hydration and was placed on bed rest for three days, after which he recovered without any reported sequelae.

In instances of acute overdosage, it is recommended that the stomach be emptied through vomiting or gastric lavage, although it is important to note that minimal drug recovery is expected if more than one hour has passed since ingestion. Given the acidic nature of ibuprofen and its urinary excretion, administering alkali and inducing diuresis may be beneficial.

Supportive measures are crucial, and the use of oral activated charcoal can be considered to reduce both the absorption and reabsorption of ibuprofen tablets. These interventions should be tailored to the individual patient's needs and clinical status.

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 that ibuprofen tablets, like other nonsteroidal anti-inflammatory drugs (NSAIDs), may lead to serious cardiovascular side effects, including myocardial infarction (MI) or stroke, which could result in hospitalization or even death. They should be advised to remain vigilant for signs and symptoms such as chest pain, shortness of breath, weakness, and slurring of speech, and to seek medical advice immediately if these occur.

It is important for patients to understand that ibuprofen tablets can cause gastrointestinal discomfort and, in rare cases, serious gastrointestinal side effects, such as ulcers and bleeding, which may also lead to hospitalization or death. Patients should be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and should seek medical attention if these symptoms arise.

Patients should be made aware that ibuprofen tablets can result in serious skin side effects, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which may necessitate hospitalization and could be fatal. They should be instructed to monitor for signs and symptoms such as skin rash, blisters, fever, or other indications of hypersensitivity, and to discontinue the medication immediately and contact their physician if any rash develops.

Patients should promptly report any signs or symptoms of unexplained weight gain or edema to their healthcare provider.

Additionally, patients should 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 symptoms occur, patients should stop therapy and seek immediate medical attention.

Patients should also be educated on the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat. In such cases, they should seek emergency help without delay.

In late pregnancy, patients should be advised to avoid ibuprofen tablets, as they may cause premature closure of the ductus arteriosus.

Finally, patients should be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed to ensure they are fully informed about the medication.

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 are advised to monitor patients on long-term NSAID treatment for signs or symptoms of gastrointestinal (GI) bleeding. Regular checks of complete blood count (CBC) and chemistry profiles are recommended for these patients. If any clinical signs indicative of liver or renal disease arise, or if abnormal liver tests persist or worsen, ibuprofen tablets should be discontinued.

Patients should be counseled on the potential serious cardiovascular side effects associated with ibuprofen tablets, including myocardial infarction (MI) and stroke, which may lead to hospitalization or death. They should also be made aware of the risk of GI discomfort and serious GI complications, such as ulcers and bleeding. Additionally, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported. Patients are encouraged to report any unexplained weight gain, edema, or signs of hepatotoxicity, such as nausea and jaundice, to their healthcare provider. Signs of an anaphylactoid reaction, including difficulty breathing and facial swelling, should also be communicated. Furthermore, ibuprofen should be avoided during late pregnancy 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)