Fexoxan Special Precautions

Gout Flare: 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.
In order to prevent gout flares when FEBUXOSTAT is initiated, concurrent prophylactic treatment with an NSAID or colchicine is recommended (see Dosage & Administration).
Cardiovascular Events: 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 (0.74 per 100 P-Y [95% Confidence Interval (CI) 0.36-1.37]) than allopurinol (0.60 per 100 P-Y [95% CI 0.16-1.53]) (see Adverse Reactions). A casual relationship with FEBUXOSTAT has not been established. Monitor for signs and symptoms of myocardial infarction (Ml) and stroke.
Hepatic Effects: There have been post-marketing reports of fatal and non-fatal hepatic failure in patients taking FEBUXOSTAT, although the reports contain insufficient information necessary to establish the probable cause. During randomized controlled studies, transaminase elevations greater than three times the upper limit of normal (ULN) were observed (AST: 2%, 2%, and ALT: 3%, 2% in FEBUXOSTAT and allopurinol-treated patients, respectively). No dose-effect relationship for these transaminase elevations was noted (see Pharmacology under Actions).
Obtain a liver test panel (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin) as a baseline before initiating FEBUXOSTAT.
Measure liver tests 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 (ALT greater than three times the upper limit of the reference range), 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.
Secondary Hyperuricemia: No studies have been conducted in patients with secondary hyperuricemia (including organ transplant recipients); FEBUXOSTAT is not recommended for use in patients whom the rate of urate formation is greatly increased (e.g., malignant disease and its treatment, Lesch-Nyhan syndrome). The concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the urinary tract.
Renal impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment (ClCr 30 to 89 mL/min). The recommended starting dose of FEBUXOSTAT is 40 mg once daily. For patients who do not achieve a sUA less than 6 mg/dL after two weeks with 40 mg, FEBUXOSTAT 80 mg is recommended. For patients with severe renal impairment (ClCr 15 to 29 mL/min), the dose of FEBUXOSTAT is limited to 40 mg once daily (see Dosage & Administration and Pharmacology under Actions).
Hepatic impairment: No dose adjustment is necessary in patients with mild to moderate hepatic impairment (Child-Pugh Class A or B). No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C); therefore, caution should be exercised in these patients (see Pharmacology under Actions).
Use in Children: Safety and effectiveness in pediatric patients under 18 years of age has not been established.
Use in the Elderly: No dose adjustment is necessary in elderly patients. Of the total number of patients in clinical studies of FEBUXOSTAT, 16% were 65 and over, while 4% were 75 and over. Comparing patients in different age groups, no clinically significant differences in safety or effectiveness were observed but greater sensitivity of some older individuals cannot be ruled out. The Cmax and AUC24 of febuxostat following multiple oral doses of FEBUXOSTAT in geriatric patients (≥65 years) were similar to those in younger patients (18 to 40 years).