Alivio

Description

Each tablet contains 800 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, healthcare professionals should exercise caution when considering the use of ibuprofen 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 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 treatment of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Warnings and Precautions

NSAIDs, including ibuprofen, are associated with significant cardiovascular risks, including an increased likelihood of serious thrombotic events, myocardial infarction, and stroke, which may be fatal. The risk of these events escalates with prolonged use, particularly in patients with existing cardiovascular disease or risk factors. It is imperative to note that ibuprofen is contraindicated for the management of peri-operative pain in patients undergoing coronary artery bypass graft (CABG) surgery.

Hypertension is another concern, as NSAIDs can induce new hypertension or exacerbate pre-existing conditions, potentially leading to a higher incidence of cardiovascular events. Therefore, blood pressure should be monitored closely during NSAID therapy.

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

Gastrointestinal adverse events are a serious risk associated with NSAID use, including inflammation, bleeding, ulceration, and perforation of the gastrointestinal tract, which can be fatal. These events may occur unexpectedly, with or without prior 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 histories.

Renal effects are also a concern, as long-term NSAID use has been linked to 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 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 can occur in individuals without prior exposure to ibuprofen, and it is crucial to avoid administering ibuprofen to patients with the aspirin triad. Emergency medical assistance should be sought immediately in the event of an anaphylactoid reaction.

Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), may arise without warning. Patients should discontinue NSAID use at the first sign of a skin rash or any indication of hypersensitivity and seek medical advice.

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 at the initiation of treatment and throughout the course of therapy. Additionally, renal function should be closely monitored in patients with advanced renal disease requiring ibuprofen.

In cases of anaphylactoid reactions, immediate emergency medical help is essential. Patients should discontinue NSAID use at the first appearance of a skin rash or any other sign of hypersensitivity and should promptly seek further evaluation and treatment if a serious gastrointestinal event is suspected.

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. Serious gastrointestinal events, including bleeding, ulceration, and perforation of the stomach or intestines, can occur at any time during treatment and may be fatal. Elderly patients are particularly at increased risk for these serious gastrointestinal complications. In patients treated for 3-6 months, upper gastrointestinal ulcers, gross bleeding, or perforation occur in approximately 1% of cases, while the incidence rises to about 2-4% in those 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. It is important to note that ibuprofen is contraindicated for the treatment of peri-operative pain in the context of coronary artery bypass graft (CABG) surgery.

Renal effects have been observed with long-term NSAID administration, including renal papillary necrosis and other forms of renal injury. Patients at heightened risk for renal toxicity include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.

Anaphylactoid reactions may occur in patients who have not previously been exposed 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), can also occur without warning and may be fatal.

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, have been reported, some resulting in fatal outcomes.

Hematological effects, including anemia, may occur in patients receiving ibuprofen, potentially due to fluid retention, occult or gross gastrointestinal blood loss, or an unclear effect on erythropoiesis. Additionally, NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients.

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.

In clinical trials involving patients with rheumatoid arthritis, reported side effects were more prevalent at doses of 3200 mg/day compared to doses of 2400 mg or less per day. Patients should be informed about the signs and symptoms of serious cardiovascular events, gastrointestinal complications, serious skin manifestations, and hepatotoxicity.

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 who are concurrently taking ACE-inhibitors.

• Diuretics: Ibuprofen has been shown to 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 assessment of diuretic efficacy is recommended during concomitant therapy.

• Warfarin-Type Anticoagulants: While short-term studies have not demonstrated a significant effect of ibuprofen on prothrombin times in patients on coumarin-type anticoagulants, there is a risk of increased bleeding. The combination of NSAIDs and anticoagulants may lead to a synergistic effect on gastrointestinal bleeding. Caution is advised when prescribing ibuprofen to patients on anticoagulants.

Pharmacokinetic Interactions

• Aspirin: Co-administration of ibuprofen with aspirin may reduce the protein binding of ibuprofen, although it does not alter the clearance of free ibuprofen. The clinical significance of this interaction is unclear, but it is generally not recommended to use ibuprofen and aspirin together due to the potential for increased adverse effects.

• Lithium: Ibuprofen can elevate plasma lithium levels and decrease renal clearance of lithium, with observed increases in mean minimum lithium concentration and reductions in renal clearance during concurrent administration. Patients should be monitored closely 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: Studies indicate that the co-administration of ibuprofen with H-2 antagonists such as cimetidine or ranitidine does not significantly affect ibuprofen serum concentrations, suggesting that no dosage adjustments are necessary in this context.

In summary, careful consideration and monitoring are advised when ibuprofen is used in conjunction with the aforementioned drug classes to mitigate potential adverse effects and ensure therapeutic efficacy.

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.

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. Regular evaluation of therapeutic outcomes and adverse effects is recommended to optimize care in this demographic.

Pregnancy

Pregnancy Category C indicates that ibuprofen tablets should be used during pregnancy only if the potential benefits justify the potential risks to the fetus. 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 to assess the safety of ibuprofen.

Healthcare professionals should be aware of the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system, particularly the closure of the ductus arteriosus. Therefore, the use of ibuprofen during late pregnancy should be avoided. Additionally, studies in rats have shown that NSAIDs, including ibuprofen, may lead to 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. Given these considerations, healthcare providers should carefully evaluate the risks and benefits 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, 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 Recommendations For acute ibuprofen 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. 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, the administration of alkali to induce diuresis may also be advantageous.

Severe Cases In a 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 for potential symptoms of ibuprofen overdosage and implement appropriate management strategies to ensure patient safety and 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 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. Healthcare providers should advise patients to be vigilant for signs and symptoms such as chest pain, shortness of breath, weakness, and slurring of speech, and to seek medical advice if they observe any of these indicative signs or symptoms.

Additionally, patients should be made aware 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. It is important for healthcare providers to instruct patients to be alert for signs and symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis, and to seek medical advice if they experience any of these symptoms.

Patients should also be informed about the potential for serious skin side effects associated with ibuprofen tablets, such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which may result in hospitalization or death. Healthcare providers should encourage patients to be aware of signs and symptoms such as skin rash and blisters, fever, or other signs of hypersensitivity, including itching, and to seek medical advice if they notice any of these symptoms.

It is essential for patients to promptly report any signs or symptoms of unexplained weight gain or edema to their physicians. Furthermore, 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 occur, patients should be instructed to discontinue therapy and seek immediate medical attention.

Patients should also be made aware of the signs of an anaphylactoid reaction, such as difficulty breathing and swelling of the face or throat, and should be advised to seek immediate emergency help if these symptoms arise. In late pregnancy, ibuprofen tablets should be avoided due to the risk of premature closure of the ductus arteriosus.

Finally, healthcare providers should encourage patients 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 and to periodically check complete blood count (CBC) and chemistry profiles. If patients exhibit clinical signs consistent with liver or renal disease, 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, as well as GI complications such as ulcers and bleeding. They should also be made aware of serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Patients are encouraged to report any unexplained weight gain, edema, or signs of hepatotoxicity, such as nausea and jaundice, and to recognize symptoms of anaphylactoid reactions. Additionally, ibuprofen should be avoided in 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)