12 (2.3%)
22 (4.3%)
40 (7.8%)
Renal failure*
11 (2.1%)
6 (1.2%)
18 (3.5%)
Nephrolithiasis
9 (1.7%)
3 (0.6%)
13 (2.5%)
Table 3: Incidence of Renal-Related Adverse Reactions by Baseline Renal Function Category 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
+ XOI
ZURAMPIC 200 mg
+ XOI
ZURAMPIC 400 mg
+ XOI
≥ 90 mL/min
n=180
n=200
n=203
Blood creatinine increased
1 (0.6%)
6 (3.0%)
12 (5.9%)
Renal failure *
0
3 (1.5%)
7 (3.4%)
≥ 60 - < 90 mL/min
n=229
n=208
n=213
Blood creatinine increased
4 (1.7%)
8 (3.8%)
21 (9.9%)
Renal failure *
4 (1.7%)
1 (0.5%)
7 (3.3%)
≥ 30 - < 60 mL/min
n=101
n=101
n=92
Blood creatinine increased
6 (5.9%)
7 (6.9%)
10 (10.9%)
Renal failure *
5 (5.0%)
2 (2.0%)
4 (4.3%)
Renal-related adverse reactions resulted in a similar discontinuation rate on ZURAMPIC 200 mg in combination with a xanthine oxidase inhibitor (1.2%) and a xanthine oxidase inhibitor alone (1%) and a higher rate on ZURAMPIC 400 mg in combination with a xanthine oxidase inhibitor (3.3%). Serious renal-related adverse reactions were reported in patients on ZURAMPIC 400 mg in combination with a xanthine oxidase inhibitor (1%) and a xanthine oxidase inhibitor alone (0.4%) and in no patients on ZURAMPIC 200 mg in combination with a xanthine oxidase inhibitor during the 12-month controlled period of the studies. Serious renal-related adverse reactions were reported with ZURAMPIC 200 mg and ZURAMPIC 400 mg in the uncontrolled long-term extensions.
Monotherapy: In a 6-month double-blind, placebo-controlled monotherapy study, renal failure (9.3%), blood creatinine increased (8.4%), and nephrolithiasis (0.9%) were reported in patients receiving ZURAMPIC 400 mg alone and in no patients receiving placebo [see WARNINGS AND PRECAUTIONS (5.1) and DOSAGE AND ADMINISTRATION (2.1)]. Serum creatinine elevations 1.5-fold or greater occurred in 24.3 % of patients receiving ZURAMPIC 400 mg and in no patients receiving placebo.
Cardiovascular Safety
Cardiovascular events and deaths were adjudicated as Major Adverse Cardiovascular Events (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) in the Phase 3 randomized controlled studies of ZURAMPIC. In the randomized controlled studies, the numbers of patients with adjudicated MACE events (incidences per 100 patient-years of exposure) were: 3 (0.71) for placebo, 4 (0.96) for ZURAMPIC 200 mg, and 8 (1.94) for ZURAMPIC 400 mg when used in combination with a xanthine oxidase inhibitor. Incidence rate ratios for ZURAMPIC 200 mg and 400 mg compared with placebo were 1.36 (95% CI: 0.23, 9.25) and 2.71 (95% CI: 0.66, 16.00), respectively.
Other Adverse Reactions
Adverse reactions occurring in 2% or more of patients on ZURAMPIC 200 mg in combination with a xanthine oxidase inhibitor and at least 1% greater than that observed in patients on placebo with a xanthine oxidase inhibitor are summarized in Table 4.
Table 4: Adverse Reactions Occurring in ≥ 2% of ZURAMPIC 200 mg-Treated Patients and at Least 1% Greater than Seen in Patients Receiving Placebo in Controlled Studies with ZURAMPIC in Combination with a Xanthine Oxidase Inhibitor (XOI)
Adverse Reaction
Placebo |
