Januvia Drug Interactions

In drug interaction studies, sitagliptin did not have clinically meaningful effects on the pharmacokinetics of the following: metformin, rosiglitazone, glyburide (glybenclamide), simvastatin, warfarin and oral contraceptives. Based on these data, sitagliptin does not inhibit CYP isozymes CYP3A4, 2C8 or 2C9. Based on in vitro data, sitagliptin is also not expected to inhibit CYP2D6, 1A2, 2C19 or 2B6 or to induce CYP3A4.
Co-administration of multiple twice-daily doses of metformin with sitagliptin did not meaningfully alter the pharmacokinetics of sitagliptin in patients with type 2 diabetes.
Population pharmacokinetic analyses have been conducted in patients with type 2 diabetes. Concomitant medications did not have a clinically meaningful effect on the pharmacokinetics of sitagliptin. Medications assessed were those that are commonly administered to patients with type 2 diabetes including cholesterol-lowering agents (e.g., statins, fibrates, ezetimibe), anti-platelet agents (e.g., clopidogrel), antihypertensives (e.g., ACE inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, hydrochlorothiazide), analgesics and non-steroidal anti-inflammatory agents (e.g., naproxen, diclofenac, celecoxib), anti-depressants (e.g., bupropion, fluoxetine, sertraline), antihistamines (e.g., cetirizine), proton-pump inhibitors (e.g., omeprazole, lansoprazole) and medications for erectile dysfunction (e.g., sildenafil).
There was a slight increase in the area under the curve (AUC, 11%) and mean peak drug concentration (C_max, 18%) of digoxin with the co-administration of sitagliptin. These increases are not considered to be clinically meaningful. Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or Januvia is recommended.
The AUC and C_max of sitagliptin were increased approximately 29% and 68%, respectively, in subjects with co-administration of a single 100-mg oral dose of JANUVIA and a single 600-mg oral dose of cyclosporine, a potent probe inhibitor of p-glycoprotein. The observed changes in sitagliptin pharmacokinetics are not considered to be clinically meaningful. No dosage adjustment for JANUVIA is recommended when co-administered with cyclosporine or other p-glycoprotein inhibitors (e.g., ketoconazole).