cal trials of another drug and may not reflect the rates observed in clinical practice.
Although other doses have been studied, the recommended dose of ZURAMPIC is 200 mg once daily in combination with a xanthine oxidase inhibitor.
In 3 randomized, placebo-controlled studies of ZURAMPIC in combination with a xanthine oxidase inhibitor (Studies 1 and 2 were with allopurinol and Study 3 was with febuxostat) for up to 12 months, a total of 511, 510, and 516 patients were treated with ZURAMPIC 200 mg, ZURAMPIC 400 mg, and placebo, respectively. The mean duration of treatment with ZURAMPIC was 11.2 months. The mean age of the population was 52 years (18-82), and 95% were males. At baseline, 62% of the patient population showed mild or moderate renal impairment (eCLcr less than 90 mL/min) and 79% of patients had at least one co-morbid condition including hypertension (65%), hyperlipidemia (45%), diabetes (17%), and kidney stones (12%).
Renal Events
ZURAMPIC causes an increase in renal uric acid excretion, which may lead to renal events including transient increases in serum creatinine, renal-related adverse reactions, and kidney stones. These renal events occurred more frequently in patients receiving ZURAMPIC 400 mg, when used as monotherapy or in combination with a xanthine oxidase inhibitor [see WARNINGS AND PRECAUTIONS (5.1)].
The number of patients with serum creatinine elevations in the 12-month placebo-controlled trials in combination with a xanthine oxidase inhibitor are shown in Table 1. Most of these elevations on ZURAMPIC 200 mg and ZURAMPIC 400 mg resolved without treatment interruption (Table 1).
Table 1: Patients with Elevated Serum Creatinine Values in the Placebo-Controlled Clinical Studies with ZURAMPIC in Combination with a Xanthine Oxidase Inhibitor (XOI)
[n (%)]
Placebo
+XOI
(N=516)
ZURAMPIC 200 mg
+XOI
(N=511)
ZURAMPIC 400 mg
+XOI
(N=510)
Serum creatinine elevation 1.5 x to < 2.0 x baseline
12 (2.3%)
20 (3.9%)
51 (10.0%)
Resolution of serum creatinine elevations by end of study
9/12 (75.0%)
18/20 (90.0%)
42/51 (82.4%)
Serum creatinine elevation ≥ 2.0 x baseline
0
9 (1.8%)
34 (6.7%)
Resolution of serum creatinine elevations by end of study
N/A
8/9 (88.9%)
26/34 (76.5%)
Renal-related adverse reactions, including blood creatinine increases and renal failure, and nephrolithiasis reported in patients receiving ZURAMPIC 200 mg, ZURAMPIC 400 mg and placebo in combination with a xanthine oxidase inhibitor are shown in Table 2 [see WARNINGS AND PRECAUTIONS (5.1)]. The incidence of reports of “blood creatinine increased” was higher with ZURAMPIC and was highest with ZURAMPIC 400 mg. Renal-related adverse reactions by baseline renal function category are shown in Table 3 [see WARNINGS AND PRECAUTIONS (5.1)]. Blood creatinine increased occurred more frequently in patients treated with ZURAMPIC in combination with a xanthine oxidase inhibitor across baseline renal function categories (Table 3).
Table 2: Incidence of Renal-Related Adverse Reactions and Nephrolithiasis in Placebo-Controlled Clinical Studies with ZURAMPIC in Combination with a Xanthine Oxidase Inhibitor (XOI)
* Renal failure includes the following adverse reactions: renal failure, renal impairment, renal failure chronic, renal failure acute, acute prerenal failure.
[n (%)]
Placebo
+XO
(N=516)
ZURAMPIC 200 mg
+XOI
(N=511)
ZURAMPIC 400 mg
+XOI
(N=510)
Blood creatinine increased |
