Vilantra Drug Interactions

Effects of other medicinal products on Sitagliptin: Clinical data described as follows suggest that the risk for clinically meaningful interactions by co-administered medicinal products is low.
In vitro studies indicated that the primary enzyme responsible for the limited metabolism of Sitagliptin is CYP3A4, with contribution from CYP2C8. In patients with normal renal function, metabolism, including via CYP3A4, plays only a small role in the clearance of Sitagliptin. Metabolism may play a more significant role in the elimination of Sitagliptin in the setting of severe renal impairment or end-stage renal disease (ESRD). For this reason, it is possible that potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of Sitagliptin in patients with severe renal impairment or ESRD.
The effect of potent CYP3A4 inhibitors in the setting of renal impairment has not been assessed in a clinical study.
In vitro transport studies showed that Sitagliptin is a substrate for p-glycoprotein and organic anion transporter-3 (OAT3). OAT3 mediated transport of Sitagliptin was inhibited in vitro by probenecid, although the risk of clinically meaningful interactions is considered to be low. Concomitant administration of OAT3 inhibitors has not been evaluated in vivo.
Metformin: Co-administration of multiple twice-daily doses of 1,000 mg metformin with 50 mg Sitagliptin did not meaningfully alter the pharmacokinetics of Sitagliptin in patients with type 2 diabetes.
Ciclosporin: A study was conducted to assess the effect of ciclosporin, a potent inhibitor of p-glycoprotein, on the pharmacokinetics of Sitagliptin. Co-administration of a single 100 mg oral dose of Sitagliptin and a single 600 mg oral dose of ciclosporin increased the AUC and Cmax of sitagliptin by approximately 29% and 68%, respectively. These changes in Sitagliptin pharmacokinetics were not considered to be clinically meaningful. The renal clearance of Sitagliptin was not meaningfully altered. Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.
Effects of Sitagliptin on other medicinal products: Digoxin: Sitagliptin had a small effect on plasma digoxin concentrations. Following administration of 0.25 mg digoxin concomitantly with 100 mg of Sitagliptin daily for 10 days, the plasma AUC of digoxin was increased on average by 11%, and the plasma Cmax on average by 18%. No dose adjustment of digoxin is recommended. However, patients at risk of digoxin toxicity should be monitored for this when Sitagliptin and digoxin are administered concomitantly.
In vitro data suggest that Sitagliptin does not inhibit nor induce CYP450 isoenzymes. In clinical studies, Sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives, providing in vivo evidence of a low propensity for causing interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT). Sitagliptin may be a mild inhibitor of p-glycoprotein in vivo.