Urinorm Special Precautions

Gout Flares: After initiation of febuxostat, an increase in gout flares is frequently observed. This increase is due to reduction in serum uric acid levels resulting in mobilization of urate from tissue deposits. Flare prophylaxis with a nonsteroidal anti-inflammatory drug (NSAID) or colchicine is recommended upon initiation of febuxostat. Prophylactic therapy may be beneficial for up to 6 months. Febuxostat treatment should not be discontinued when gout flares occur. The gout flare should be managed concurrently, as appropriate for the individual patient.
Cardiovascular Events: Treatment with febuxostat in patients with ischemic heart disease or congestive heart failure is not recommended.
In the randomized controlled studies, there was a higher rate of cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions and non-fatal strokes) in patients treated with febuxostat than with allopurinol. A causal relationship with febuxostat has not been established. Signs and symptoms of myocardial infarction and stroke should be monitored.
Hepatic Effects: There have been postmarketing reports of fatal and non-fatal hepatic failure in patients taking febuxostat, although the reports contain insufficient information necessary to establish the probable cause. Serum transaminase concentrations exceeding 3 times the upper limit of normal have been reported in patients receiving febuxostat. Laboratory assessment of liver function is recommended prior to initiation of febuxostat therapy and periodically thereafter.
A liver test panel [serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin] should be obtained as a baseline before initiating febuxostat.
Liver tests should be measured promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. In this clinical context, if the patient is found to have abnormal liver tests, febuxostat treatment should be interrupted and investigation done to establish the probable cause. Febuxostat should not be restarted in these patients without another explanation for the liver test abnormalities. Patients who have serum ALT greater than three times the reference range with serum total bilirubin greater than two times the reference range without alternative etiologies are at risk for severe drug-induced liver injury and should not be restarted on febuxostat. For patients with lesser elevations of serum ALT or bilirubin and with an alternate probable cause, treatment with febuxostat can be used with caution.
Medicinal Product Allergy/Hypersensitivity: Rare reports of serious allergic/hypersensitivity reactions, including life-threatening Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and acute anaphylactic reaction/shock, have been reported in post-marketing experience. In most cases, these reactions occurred during the first month of therapy with febuxostat. Some, but not all of these patients reported renal impairment and/or previous hypersensitivity to allopurinol. Severe hypersensitivity reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS) were associated with fever, hematological, renal or hepatic involvement in some cases.
Patients should be advised of the signs and symptoms and monitored closely for symptoms of allergic/hypersensitivity reactions. Febuxostat treatment should be immediately stopped if serious allergic/hypersensitivity reactions, including SJS, occur since early withdrawal is associated with a better prognosis. If patient has developed allergic/hypersensitivity reactions and acute anaphylactic reaction/shock, febuxostat must not be re-started in this patient at any time.
Thyroid Disorders: Increased thyroid stimulating hormone values (>5.5 μIU/mL) were observed in patients on long-term treatment with febuxostat (5.5%). Caution is required when febuxostat is used in patients with alteration of thyroid function.
Secondary Hyperuricemia: No studies have been conducted in patients with secondary hyperuricemia (including organ transplant recipients). Febuxostat is not recommended for use in patients whose rate of urate formation is greatly increased (e.g., malignant disease and its treatment, Lesch-Nyhan syndrome). In rare cases, the concentration of xanthine in urine could rise sufficiently to allow deposition in the urinary tract.
Other Diseases: Febuxostat is not recommended for use in patients with a greatly increased rate of urate formation (e.g., malignant disease and its treatment, Lesch-Nyhan syndrome). No studies have been conducted in these populations.
Febuxostat has not been studied in organ transplant patients.
Hepatic Impairment: No dose adjustment is necessary in patients with mild or moderate hepatic impairment. No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C), thus, caution should be exercised in these patients.
Renal Impairment: No dose adjustment is necessary in patients with mild or moderate renal impairment. There are insufficient data in patients with severe renal impairment (creatinine clearance less than 30 mL/min); therefore, caution should be exercised in these patients.
Effects on Ability to Drive and Use Machine: Somnolence, dizziness, paresthesia and blurred vision have been reported with the use of febuxostat. Patients should exercise caution before driving, using machinery or participating in dangerous activities until they are reasonably certain that febuxostat does not adversely affect performance.
Use in Children (<18 years old): The safety and efficacy of febuxostat have not been established in pediatric patients.
Use in Elderly (≥ 65 years old): No dose adjustment is necessary in elderly patients. The C_max and AUC₂₄ of febuxostat following multiple oral doses in geriatric subjects were similar to those in younger subjects (18 to 40 years old).