Cationic drugs: Certain medications used concomitantly with Metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretions (e.g.: amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, ranitidine, or vancomycin) may decrease Metformin elimination by competing for common renal tubular transport systems. Hence, careful patient monitoring and dose adjustment of Metformin and/or interfering cationic drug is recommended.
Miconazole (systemic route, oromucosal gel) and Phenylbutazone (systemic route): Increases hypoglycemic effect of Gliclazide.
Furosemide: A single-dose, Metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by co-administration. Furosemide increased the Metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in Metformin renal clearance. When administered with Metformin, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of Metformin and furosemide when co-administered chronically.
Vitamin B12: Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium dependent binding of the intrinsic factor vitamin B12 complex to its receptor. The reaction very rarely results in pernicious anemia that is reversible with discontinuation of Metformin or with vitamin B12 supplementation.
Nifedipine: Nifedipine appears to enhance the absorption of Metformin, it increases plasma Metformin Cmax and AUC by 20% and 9% respectively and increases the amount of Metformin excreted in the urine. Metformin has minimal effects on nifedipine.
Salicylates: If salicylates are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control.
Thiazide: Interactions between thiazide diuretics and oral antidiabetic agents decreases insulin sensitivity thereby leading to glucose intolerance and hyperglycemia, thus leading to a loss of diabetic control. Hence diabetic patients should be monitored closely. Concomitant administration of angiotensin enzyme inhibitors (captopril, enalapril), other antidiabetic drugs (insulin, acarbose) beta-blockers, fluconazole, histamine (H2) receptor antagonist, monoamine oxidase inhibitors (MAOIs), sulphonamides and non-steroidal anti-inflammatory agents increases sensitivity to insulin and potentiation of blood glucose lowering effect and thus, in some instances, hypoglycemia may occur. Dosage of the oral antidiabetic agent may need to be reduced. Patients receiving estrogens or oral contraceptives, phenytoin, quinolones should be closely monitored for loss of diabetic control when therapy is instituted or discontinued.