RiteMED Metformin HCl Drug Interactions

Tablet: Antidiabetic Agents: Acarbose reduced the bioavailability of metformin. In patients with type 2 diabetes mellitus, co-administration of glibenclamide with metformin showed variable decrease in the area under the blood concentration-time curve (AUC) and peak blood concentration of glibenclamide.
Diuretics: Thiazide diuretics can exacerbate diabetes mellitus resulting in increased requirements of oral antidiabetic agents, temporary loss of diabetic control or secondary failure to antidiabetic agent. Concomitant administration of furosemide and metformin increased the peak plasma and blood concentrations of metformin by approximately 22%, AUC of metformin by approximately 15%; peak plasma furosemide concentrations and AUC by approximately 31% and 12%, respectively. Half-life of furosemide was decreased by 32%.
Nifedipine: Concomitant administration of metformin and nifedipine in healthy individuals enhanced the absorption and increased the urinary excretion of metformin.
Drugs eliminated by renal tubular secretion (ie, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin): May cause an increase in metformin peak plasma, whole blood concentrations and whole blood AUC.
Cimetidine: In single- and multiple-dose studies in healthy individuals, concomitant administration of cimetidine and metformin increased the peak plasma and whole blood concentrations of metformin by approximately 60-81% and the AUC of metformin by approximately 40-50%.
β-Adrenergic Blocking Agents: β-adrenergic blocking agents may impair glucose tolerance; increase the frequency and severity of hypoglycemia; block hypoglycemia-induced tachycardia and increase hypoglycemic sweating; delay the rate of recovery of blood glucose concentration following drug-induced hypoglycemia; alter hemodynamic response and impair peripheral circulation.
Alcohol: Combined use of alcohol and metformin increases the risk of hypoglycemia and lactic acidosis.
Angiotensin-Converting Enzyme (ACE) Inhibitors: ACE inhibitors (eg, captopril, enalapril) reduce fasting blood glucose concentration in nondiabetic individuals and increase insulin sensitivity.
Others: Drugs that cause hyperglycemia and may exacerbate glycemic control in patients with diabetes mellitus include corticosteroids, oral contraceptives, sympathomimetics, phenothiazines, niacin, calcium-channel blocking agents and isoniazid.
Sustained-release tablet: Cationic Drugs: Cationic drugs such as amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin that are eliminated by renal tubular secretion, theoretically may cause an increase in metformin peak plasma concentrations, whole blood concentrations and whole blood AUC by competing with metformin for common renal tubular transport systems. Concomitant administration of metformin and cimetidine has been observed to result in reduced urinary metformin excretion and increased plasma metformin concentrations.
Other Antidiabetic Agents: Hypoglycemia may occur when metformin is used concomitantly with other antidiabetic agents such as sulfonylureas, meglitinides, glitazones, or insulin.
Diuretics: Thiazide diuretics may exacerbate diabetes mellitus and may result in increased requirements of oral antidiabetic agents, metformin included. Temporary loss of diabetic control or secondary failure to the antidiabetic agent may also occur. Potassium-sparing diuretics, which are less diabetogenic, may be considered as a substitute.
Furosemide may increase metformin plasma and blood concentrations and blood AUC without significantly affecting metformin renal clearance.
Nifedipine: Nifedipine increases the absorption, C_max and AUC of metformin, and increases metformin excretion in the urine. Metformin has minimal effects on nifedipine pharmacokinetics.
β-Adrenergic Blocking Agents: β-adrenergic blocking agents (e.g., propranolol, nadolol) may impair glucose tolerance and mask the true frequency or severity of hypoglycemia, block hypoglycemia-induced tachycardia but not hypoglycemic sweating, delay the rate of recovery of blood glucose concentration following drug-induced hypoglycemia, and impair peripheral circulation. Use these drugs with caution in patients with type 2 diabetes.
Protein-Bound Drugs: Interaction of metformin and highly protein-bound drugs (e.g., salicylates, sulfonamides, chloramphenicol, probenecid) is unlikely because metformin is negligibly bound to plasma proteins.
Angiotensin-Converting Enzyme (ACE) Inhibitors: ACE inhibitors (e.g., captopril, enalapril) may reduce fasting blood glucose concentrations. These drugs have also been associated with unexplained hypoglycemia in diabetic patients. Caution should be exercised when administering metformin together with ACE inhibitors to prevent severe hypoglycemia.
Alcohol: There is an increased risk of hypoglycemia and lactic acidosis when alcohol and metformin are used concomitantly since alcohol decreases lactate clearance and hepatic gluconeogenesis, and may increase insulin secretion. Acute or chronic intake of alcohol should be avoided in patients receiving metformin therapy.
Clomifene: Ovulatory response may be increased when clomifene and metformin are used concomitantly in premenopausal patients with polycystic ovary syndrome.
Anticoagulants: Metformin may affect the pharmacokinetic properties of coumarin anticoagulants when administered concomitantly. An increase in prothrombin time may occur upon cessation of metformin therapy, with an increased risk of hemorrhage. Patients receiving phenprocoumon or other vitamin K anticoagulants should be carefully monitored.
Iodinated Contrast Media: Intravascular administration of iodinated contrast media may lead to renal failure, resulting in metformin accumulation with the risk of lactic acidosis. Metformin should be discontinued prior to, or at the time of the procedure, and withheld for 48 hours afterwards. Metformin may be reinstituted only after renal function has been re-evaluated and found to be normal.
Glyburide: Concomitant administration of metformin and glyburide produced no changes in metformin pharmacokinetics and pharmacodynamics. Decreases in C_max, blood AUC of glyburide were observed, but were highly variable. The clinical significance of this finding was unclear.
Others: Drugs that may cause hyperglycemia and may exacerbate loss of glycemic control in patients with diabetes include 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 in patients.
The pharmacokinetics of metformin and propranolol, and metformin and ibuprofen were not affected when coadministered in single-dose interaction studies in healthy volunteers.