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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.
Cardiovascular Events: In the randomized, controlled studies, there was a higher rate of cardiovascular thromboembolic events (cardiovascular deaths, nonfatal myocardial infarctions and nonfatal strokes) in patients treated with febuxostat [0.74/100 P-Y (95% Cl 0.36-1.37)] than allopurinol [0.60/100 P-Y (95% Cl 0.16 -1.53 ]. A casual relationship with febuxostat has not been established. Monitor for signs and symtoms of myocardial infarction and stroke.
Liver Enzyme Elevations: During randomized, controlled studies, transaminase elevations >3 times the upper limit of normal (ULN) were observed [aspartate aminotransferase (AST): 2%, 2% and alanine aminotransferase (ALT): 3%, 2% in febuxostat and allopurinol-treated patients, respectively]. No dose-effect relationship for these transaminase elevations was noted. Laboratory assessment of liver function is recommended at eg, 2 and 4 months following initiation of febuxostat and periodically thereafter.
Renal Impairment: No dose adjustment is necessary in patients with mild or moderate renal impairment (CrCl 30-89 mL/min). The recommended starting dose of febuxostat is 40 mg once daily. For patients who do not achieve a serum uric acid <6 mg/dL after 2 weeks with 40 mg, febuxostat 80 mg is recommended. There are insufficient data in patients with severe renal impairment (CrCl <30 mL /min); therefore, caution should be exercised in these patients.
Hepatic Impairment: No dose adjustment is necessary in patients with Child-Pugh class A or B. No studies have been conducted in patients with Child-Pugh class C; therefore, caution should be exercised in these patients.
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 (eg, 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.
Use in lactation: Febuxostat is excreted in the milk of rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when febuxostat is administered to a nursing woman.
Use in children: Safety and effectiveness in pediatric patients <18 years of age have not been established.
Use in the elderly: No dose adjustment is necessary in elderly patients. Of the total number of subjects in clinical studies of febuxostat, 16% were ≥65, while 4% were ≥75. Comparing subjects 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 subjects (=65 years) were similar to those in younger subjects (18-40 years).
