Fliptin Drug Interactions

Effects of sitagliptin on other drugs: Sitagliptin did not alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives.
Sitagliptin is not an inhibitor of CYP3A4, CYP2C8, CYP2C9 isozymes, and organic cationic transporter (OCT).
Digoxin: Sitagliptin had a minimal effect on the pharmacokinetics of digoxin. Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or sitagliptin.
Metformin: Coadministration of multiple twice-daily doses of sitagliptin with metformin, an OCT substrate, did not meaningfully alter the pharmacokinetics of metformin in patients with type 2 diabetes. Therefore, sitagliptin is not an inhibitor of OCT-mediated transport.
Sulfonylurea: Single-dose pharmacokinetics of glyburide, a CYP2C9 substrate, was not meaningfully altered in patients receiving multiple doses of sitagliptin. Clinically meaningful interactions would not be expected with other sulfonylureas (e.g., glipizide, tolbutamide, and glimepiride) which, like glyburide, are primarily eliminated by CYP2C9. However, the risk of hypoglycemia from the coadministration of sitagliptin and sulfonylureas is unknown.
Simvastatin: Single-dose pharmacokinetics of simvastatin, a CYP3A4 substrate, was not meaningfully altered in patients receiving multiple daily doses of sitagliptin. Therefore, sitagliptin is not an inhibitor of CYP3A4-mediated metabolism.
Warfarin: Multiple daily doses of sitagliptin did not meaningfully alter the pharmacokinetics or pharmacodynamics of a single dose of warfarin. Because S(-) warfarin is primarily metabolized by CYP2C9, these data also support the conclusion that sitagliptin is not a CYP2C9 inhibitor.
Oral contraceptives: Coadministration with sitagliptin did not meaningfully alter the steady-state pharmacokinetics of norethindrone or ethinyl estradiol.
Effects of other drugs on sitagliptin: Metformin: Coadministration of multiple twice-daily doses of metformin with sitagliptin did not meaningfully alter the pharmacokinetics of sitagliptin in patients with type 2 diabetes.
Ciclosporin: Coadministration of a single 100 mg oral dose of sitagliptin and a single 600 mg oral dose of ciclosporin, a potent inhibitor of p-glycoprotein, increased the AUC and C_max of sitagliptin but these changes were not considered to be clinically meaningful. The renal clearance of sitagliptin was also not meaningfully altered. Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.