y). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 7-20, lesinurad was not teratogenic and did not affect fetal development at exposures up to approximately 10 times the MRHD (on an AUC basis at maternal oral doses up to 75 mg/kg/day). Severe maternal toxicity, including mortality, was observed in rats and rabbits at exposures equal to or greater than approximately 45 and 4 times the MRHD (on an AUC basis at maternal oral doses of 300 mg/kg/day in rats and 25 mg/kg/day and higher in rabbits), respectively.
In a pre- and postnatal development study in pregnant female rats dosed from gestation day 7 through lactation day 20, lesinurad had no effects on delivery or growth and development of offspring at a dose approximately 5 times the MRHD (on a mg/m2 basis at a maternal dose oral dose of 100 mg/kg/day). In rats, plasma and milk concentrations of lesinurad were approximately equal.
8.2 Lactation
Risk Summary
There is no information regarding the presence of ZURAMPIC in human milk, the effects on the breastfed infant, or the effects on milk production. Lesinurad is present in the milk of rats [see USE IN SPECIFIC POPULATIONS (8.1)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZURAMPIC and any potential adverse effects on the breastfed infant from ZURAMPIC or from the underlying maternal condition.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients under 18 years of age have not been established.
8.5 Geriatric Use
No dose adjustment is necessary in elderly patients. In a pool of clinical safety and efficacy studies of ZURAMPIC in gout patients, 13% were 65 years and older and 2% were 75 years and older. No overall differences between lesinurad and placebo in safety and effectiveness were observed between these subjects and younger subjects but greater sensitivity of some older individuals cannot be ruled out.
8.6 Renal Impairment
The pharmacokinetics (PK) of ZURAMPIC was eva luated in studies that included patients with mild (eCLcr 60 to less than 90 mL/min), moderate (eCLcr 30 to less than 60 mL/min), and severe renal impairment (eCLcr less than 30 mL/min). Lesinurad exposure (AUC) increased by 30%, 50-73%, and 113%, respectively, in subjects with mild, moderate, and severe renal impairment [see CLINICAL PHARMACOLOGY (12.3)].
The efficacy and safety of ZURAMPIC were eva luated in studies that included gout patients with mild and moderate renal impairment [seeADVERSE REACTIONS (6) and CLINICAL STUDIES (14)]. There were no clear differences in safety and effectiveness of ZURAMPIC in patients with mild renal impairment compared to patients with normal renal function and no dose adjustment is recommended [see DOSAGE AND ADMINISTRATION (2.4) and CLINICAL STUDIES (14)].
Across all ZURAMPIC and placebo treatment groups, patients with moderate renal impairment had a higher occurrence of renal related adverse reactions compared to patients with mild renal impairment or normal renal function [see ADVERSE REACTIONS (6.1)]. The experience with ZURAMPIC in patients with an eCLcr less than 45 mL/min is limited and there was a trend toward lesser efficacy [see CLINICAL STUDIES (14.5)]. ZURAMPIC should not be initiated in patients with an eCLcr less than 45 mL/min. No dose adjustment is recommended in patients with an eCLcr 45 to less than 60 mL/min, however, more frequent renal function monitoring is recommended. ZURAMPIC sh |
