Overall, a higher rate of APTC events was observed in ULORIC than in allopurinol-treated patients. A causal relationship with ULORIC has not been established. Monitor for signs and symptoms of MI and stroke.

ULORIC is an XO inhibitor. Drug interaction studies of ULORIC with drugs that are metabolized by XO (e.g., theophylline, mercaptopurine, azathioprine) have not been conducted. Inhibition of XO by ULORIC may cause increased plasma concentrations of these drugs leading to toxicity [see Clinical Pharmacology (12.3)]. ULORIC is contraindicated in patients being treated with azathioprine, mercaptopurine, or theophylline [see Contraindications (4)].

Drug interaction studies of ULORIC with cytotoxic chemotherapy have not been conducted. No data are available regarding the safety of ULORIC during cytotoxic chemotherapy.

Based on drug interaction studies in healthy subjects, ULORIC does not have clinically significant interactions with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin or desipramine [see Clinical Pharmacology (12.3)]. Therefore, ULORIC may be used concomitantly with these medications.

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. ULORIC should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Febuxostat was not teratogenic in rats and rabbits at oral doses up to 48 mg per kg (40 and 51 times the human plasma exposure at 80 mg per day for equal body surface area, respectively) during organogenesis. However, increased neonatal mortality and a reduction in the neonatal body weight gain were observed when pregnant rats were treated with oral doses up to 48 mg per kg (40 times the human plasma exposure at 80 mg per day) during organogenesis and through lactation period.

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 ULORIC is administered to a nursing woman.

Safety and effectiveness in pediatric patients under 18 years of age have not been established.

No dose adjustment is necessary in elderly patients. Of the total number of subjects in clinical studies of ULORIC, 16 percent were 65 and over, while 4 percent were 75 and over. 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 C and AUC of febuxostat following multiple oral doses of ULORIC in geriatric subjects (≥ 65 years) were similar to those in younger subjects (18-40 years) [see Clinical Pharmacology (12.3)].

No dose adjustment is necessary in patients with mild or moderate renal impairment (Cl 30-89 mL per min). The recommended starting dose of ULORIC is 40 mg once daily. For patients who do not achieve a sUA less than 6 mg per dL after 2 weeks with 40 mg, ULORIC 80 mg is recommended.

There are insufficient data in patients with severe renal impairment (Cl less than 30 mL per min); therefore, caution should be exercised in these patients [see Clinical Pharmacology (12.3)].

No dose adjustment is necessary in patients with mild or 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 [