Galvus Met: No clinically relevant pharmacokinetic interaction was observed when vildagliptin (100 mg once daily) was co-administered with metformin HCl (1000 mg once daily). Drug interactions for each component of Galvus Met has been extensively studied. However, the concomitant use of vildagliptin/metformin HCl 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 CYP450 enzyme substrate nor does it inhibit, nor induces CYP450 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 metabolised by CYP 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 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 HCl), amlodipine, digoxin, ramipril, simvastatin, valsartan or warfarin were observed after co-administration with vildagliptin.
Metformin HCl: The following is known for metformin component: Furosemide: Furosemide increased Cmax and blood AUC of metformin with no change in renal clearance of metformin. Metformin decreased Cmax, blood AUC of furosemide, with no change in renal clearance of furosemide.
Nifedipine: Nifedipine increased absorption, Cmax and AUC of metformin, and increased excretion of metformin in urine. Metformin had minimal effects on nifedipine.
Glyburide: Glyburide produced no changes in metformin pharmacokinetic/pharmacodynamic (PK/PD) parameters. Decreases in Cmax, blood AUC of glyburide were observed, but were highly variable. Therefore, the clinical significance of this finding was unclear.
Cationic Drugs: Cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Thus, with cimetidine increases in metformin plasma/blood concentration and AUC were observed to be 60% and 40%, respectively. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful monitoring of patients and doses of metformin and such medications are recommended.
Other: 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 of Galvus Met. Avoid consumption of alcohol and medicinal products containing alcohol. (See Precautions.)
Incompatibilities: Not applicable.