Vascular Disorders: flushing, hot flush, hypertension, hypotension.

Laboratory Parameters: activated partial thromboplastin time prolonged, creatine increased, bicarbonate decreased, sodium increased, EEG abnormal, glucose increased, cholesterol increased, triglycerides increased, amylase increased, potassium increased, TSH increased, platelet count decreased, hematocrit decreased, hemoglobin decreased, MCV increased, RBC decreased, creatinine increased, blood urea increased, BUN/creatinine ratio increased, creatine phosphokinase (CPK) increased, alkaline phosphatase increased, LDH increased, PSA increased, urine output increased/decreased, lymphocyte count decreased, neutrophil count decreased, WBC increased/decreased, coagulation test abnormal, low density lipoprotein (LDL) increased, prothrombin time prolonged, urinary casts, urine positive for white blood cells and protein.

Cardiovascular Safety

Cardiovascular events and deaths were adjudicated to one of the pre-defined endpoints from the Anti-Platelet Trialists' Collaborations (APTC) (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) in the randomized controlled and long-term extension studies. In the Phase 3 randomized controlled studies, the incidences of adjudicated APTC events per 100 patient-years of exposure were: Placebo 0 (95% CI 0.00-6.16), ULORIC 40 mg 0 (95% CI 0.00-1.08), ULORIC 80 mg 1.09 (95% CI 0.44-2.24), and allopurinol 0.60 (95% CI 0.16-1.53).

In the long-term extension studies, the incidences of adjudicated APTC events were: ULORIC 80 mg 0.97 (95% CI 0.57-1.56), and allopurinol 0.58 (95% CI 0.02-3.24).

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.

6.2 Postmarketing Experience
Adverse reactions have been identified during post approval use of ULORIC. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship.

Immune System Disorders: anaphylaxis, anaphylactic reaction.
Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis.
Psychiatric Disorders: psychotic behavior including aggressive thoughts.
Renal and Urinary Disorders: tubulointerstitial nephritis.
Skin and Subcutaneous Tissue Disorders: generalized rash, Stevens Johnson Syndrome, hypersensitivity skin reactions.

7 DRUG INTERACTIONS
7.1 Xanthine Oxidase Substrate Drugs
ULORIC is an XO inhibitor. Based on a drug interaction study in healthy subjects, febuxostat altered the metabolism of theophylline (a substrate of XO) in humans [see Clinical Pharmacology (12.3)]. Therefore, use with caution when co-administering ULORIC with theophylline.

Drug interaction studies of ULORIC with other drugs that are metabolized by XO (e.g., mercaptopurine and 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 azat