ProglinMet Drug Interactions

Vildagliptin/Metformin: No clinically relevant pharmacokinetic interaction was observed when vildagliptin (100 mg once daily) was co-administered with metformin hydrochloride (1,000 mg once daily).
Drug interactions for each component have been extensively studied. However, the concomitant use of the active substances in patients in clinical studies and in widespread clinical use has not resulted in any unexpected interactions.
The following statements reflect the information available on the individual active substances (vildagliptin and metformin).
Vildagliptin: Vildagliptin has a low potential for drug interactions. Since vildagliptin is not a cytochrome P (CYP) 450 enzyme substrate nor does it inhibit nor induce CYP 450 enzymes, it is not likely to interact with co-medications that are substrates, inhibitors or inducers of these enzymes.
Furthermore, vildagliptin does not affect metabolic clearance of co-medications metabolized by CYP 1A2, CYP 2C8, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1, and CYP 3A4/5. Drug-drug interaction studies were conducted with commonly co-prescribed medications for patients with type 2 diabetes or medications with a narrow therapeutic window. As a result of these studies, no clinically relevant interactions with other oral antidiabetics (glibenclamide, pioglitazone, metformin hydrochloride), amlodipine, digoxin, ramipril, simvastatin, valsartan or warfarin were observed after co-administration with vildagliptin.
Metformin Hydrochloride: The following is known for metformin component: Furosemide: Furosemide increased C_max and blood AUC of metformin with no change in renal clearance of metformin. Metformin decreased C_max, blood AUC of furosemide, with no change in renal clearance of furosemide.
Nifedipine: Nifedipine increased absorption, C_max and AUC of metformin, and increased excretion of metformin in urine. Metformin had minimal effects on nifedipine.
Glyburide: Glyburide produced no changes in metformin PK/PD parameters. Decreases in C_max, blood AUC of glyburide were observed, but were highly variable. Therefore the clinical significance of this finding was unclear.
Iodinated contrast agents: Metformin-containing products [such as vildagliptin + metformin (ProglinMet)] must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable (see Dosage & Administration and Precautions).
Drugs that reduce metformin clearance: Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin.
Other: Some drugs can adversely affect renal function which may increase the risk of lactic acidosis, e.g., NSAIDs, including selective cyclooxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with metformin-containing products (such as vildagliptin + metformin (ProglinMet)), close monitoring of renal function is necessary. Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. Close monitoring of glycemic control and metformin dose adjustments are recommended when such drugs are administered or withdrawn for these patients.
There is an increased risk of lactic acidosis in acute alcohol intoxication (particularly in the case of fasting, malnutrition or hepatic insufficiency) due to the metformin active substance. Avoid consumption of alcohol and medicinal products containing alcohol (see Precautions).