decreased by approximately 13%, and Cmax decreased by approximately 21% compared to subjects with normal hepatic function. This decrease in ertugliflozin exposure is not considered clinically meaningful. There is no clinical experience in patients with Child-Pugh class C (severe) hepatic impairment. The plasma protein binding of ertugliflozin was unaffected in patients with moderate hepatic impairment [see Use in Specific Populations (8.7)].
Metformin hydrochloride
No pharmacokinetic studies of metformin have been conducted in patients with hepatic impairment [see Use in Specific Populations (8.7)].
Pediatric Patients
No studies with SEGLUROMET have been performed in pediatric patients.
Effects of Age, Body Weight, Gender, and Race
Ertugliflozin
Based on a population pharmacokinetic analysis, age, body weight, gender, and race do not have a clinically meaningful effect on the pharmacokinetics of ertugliflozin.
Metformin hydrochloride
Limited data from controlled pharmacokinetic studies of metformin in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and Cmax is increased, compared to 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.
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 in patients with type 2 diabetes mellitus, the antihyperglycemic effect was comparable in Whites (n=249), Blacks (n=51), and Hispanics (n=24).
Drug Interaction Studies
SEGLUROMET
Coadministration of single dose of ertugliflozin (15 mg) and metformin (1,000 mg) did not meaningfully alter the pharmacokinetics of either ertugliflozin or metformin in healthy subjects.
Pharmacokinetic drug interaction studies with SEGLUROMET have not been performed; however, such studies have been conducted with ertugliflozin and metformin, the individual components of SEGLUROMET.
Ertugliflozin
In Vitro Assessment of Drug Interactions
In in vitro studies, ertugliflozin and ertugliflozin glucuronides did not inhibit CYP450 isoenzymes (CYPs) 1A2, 2C9, 2C19, 2C8, 2B6, 2D6, or 3A4, and did not induce CYPs 1A2, 2B6, or 3A4. Ertugliflozin was not a time-dependent inhibitor of CYP3A in vitro. Ertugliflozin did not inhibit UGT1A6, 1A9, or 2B7 in vitro and was a weak inhibitor (IC50 >39 µM) of UGT1A1 and 1A4. Ertugliflozin glucuronides did not inhibit UGT1A1, 1A4, 1A6, 1A9, or 2B7 in vitro. Overall, ertugliflozin is unlikely to affect the pharmacokinetics of drugs eliminated by these enzymes. Ertugliflozin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters and is not a substrate of orga
