SYNJARDYXR(empagliflozin and metformin hydrochloride extended-release) tablets(二十二)
tients with decreased renal function (based on measured eGFR), the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in eGFR [see CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.1)].
Hepatic Impairment
SYNJARDY XR: Studies characterizing the pharmacokinetics of empagliflozin and metformin after administration of SYNJARDY XR in hepatically impaired patients have not been performed [see WARNINGS AND PRECAUTIONS (5.1)].
Empagliflozin: In subjects with mild, moderate, and severe hepatic impairment according to the Child-Pugh classification, AUC of empagliflozin increased by approximately 23%, 47%, and 75%, and Cmax increased by approximately 4%, 23%, and 48%, respectively, compared to subjects with normal hepatic function.
Metformin hydrochloride: No pharmacokinetic studies of metformin have been conducted in patients with hepatic impairment.
Effects of Age, Body Mass Index, Gender, and Race
Empagliflozin: Based on the population PK analysis, age, body mass index (BMI), gender and race (Asians versus primarily Whites) do not have a clinically meaningful effect on pharmacokinetics of empagliflozin [see USE IN SPECIFIC POPULATIONS (8.5)].
Metformin hydrochloride: Metformin pharmacokinetic parameters did not differ significantly between normal subjects and patients with type 2 diabetes mellitus when analyzed according to gender. Similarly, in controlled clinical studies in patients with type 2 diabetes mellitus, the antihyperglycemic effect of metformin was comparable in males and females.
No studies of metformin pharmacokinetic parameters according to race have been performed. In controlled clinical studies of metformin hydrochloride in patients with type 2 diabetes mellitus, the antihyperglycemic effect was comparable in Caucasians (n=249), Blacks (n=51), and Hispanics (n=24).
Geriatric
SYNJARDY XR: Studies characterizing the pharmacokinetics of empagliflozin and metformin after administration of SYNJARDY XR in geriatric patients have not been performed [see WARNINGS AND PRECAUTIONS (5.2, 5.4) and USE IN SPECIFIC POPULATIONS (8.5)].
Empagliflozin: Age did not have a clinically meaningful impact on the pharmacokinetics of empagliflozin based on a population pharmacokinetic analysis [see USE IN SPECIFIC POPULATIONS (8.5)].
Metformin hydrochloride: Limited data from controlled pharmacokinetic studies of metformin hydrochloride in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and Cmax is increased, compared with healthy young subjects. From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function.
Pediatric
Studies characterizing the pharmacokinetics of empagliflozin or metformin after administration of SYNJARDY XR in pediatric patients have not been performed.
Drug Interactions
Pharmacokinetic drug interaction studies with SYNJARDY XR have not been performed; however, such studies have been conducted with the individual components empagliflozin and metformin hydrochloride.
Empagliflozin
In vitro Assessment of Drug Interactions: Empagliflozin does not inhibit, inactivate, or induce CYP450 isoforms. In vitro data suggest that the primary route of metabolism of empagliflozin in humans is g |
