hy control subjects. The study included patients with renal impairment classified on the basis of creatinine clearance as mild (50 to <80 mL/min), moderate (30 to <50 mL/min), and severe (<30 mL/min), as well as patients with ESRD on hemodialysis. In addition, the effects of renal impairment on sitagliptin pharmacokinetics in patients with type 2 diabetes and mild or moderate renal impairment were assessed using population pharmacokinetic analyses. Creatinine clearance was measured by 24-hour urinary creatinine clearance measurements or estimated from serum creatinine based on the Cockcroft-Gault formula:
CrCl = [140 - age (years)] × weight (kg) {× 0.85 for female patients}
[72 × serum creatinine (mg/dL)]
Compared to normal healthy control subjects, an approximate 1.1- to 1.6-fold increase in plasma AUC of sitagliptin was observed in patients with mild renal impairment. Because increases of this magnitude are not clinically relevant, dosage adjustment in patients with mild renal impairment is not necessary. Plasma AUC levels of sitagliptin were increased approximately 2-fold and 4-fold in patients with moderate renal impairment and in patients with severe renal impairment, including patients with ESRD on hemodialysis, respectively. JUVISYNC should not be used in patients with moderate or severe renal impairment. [See Dosage and Administration (2.2); Warnings and Precautions (5.4).]
Hepatic Impairment
Sitagliptin
In patients with moderate hepatic impairment (Child-Pugh score 7 to 9), mean AUC and Cmax of sitagliptin increased approximately 21% and 13%, respectively, compared to healthy matched controls following administration of a single 100 mg dose of sitagliptin. These differences are not considered to be clinically meaningful.
There is no clinical experience in patients with severe hepatic impairment (Child-Pugh score >9).
Body Mass Index (BMI)
Sitagliptin
Body mass index had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.
Gender
Sitagliptin
Gender had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.
Geriatric
Sitagliptin
When the effects of age on renal function are taken into account, age alone did not have a clinically meaningful impact on the pharmacokinetics of sitagliptin based on a population pharmacokinetic analysis. Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of sitagliptin compared to younger subjects.
Simvastatin
In a study including 16 elderly patients between 70 and 78 years of age who received simvastatin 40 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18-30 years of age. [see Warnings and Precautions (5.2); Use in Specific Populations (8.5)].
Pediatric
Sitagliptin
Studies characterizing the pharmacokinetics of sitagliptin in pediatric patients have not been performed.
Race
Sitagliptin
Race had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of available pharmacokinetic data, including subjects of white |
