RiteMED Metformin Extended-Release Tablet 1 g Drug Interactions

Carbonic Anhydrase Inhibitors: Carbonic anhydrase inhibitors (e.g., topiramate, zonisamide, acetazolamide or dichlorphenamide) frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with metformin may increase the risk for lactic acidosis. Consider more frequent monitoring of these patients.
Organic Cation Transporters (OCT)/Multidrug and Toxin Extrusion (MATE) Inhibitors: Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., OCT2/MATE inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis.
Coadministration of metformin with inhibitors of OCT1 (e.g., verapamil) may reduce efficacy of metformin. Inducers of OCT1 (e.g., rifampicin) may increase gastrointestinal absorption and efficacy of metformin. Inhibitors of OCT2 (e.g., cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration. Inhibitors of both OCT1 and OCT2 (e.g., crizotinib, olaparib) may alter efficacy and renal elimination of metformin. Therefore, caution is advised particularly in patients with renal impairment, when these drugs are co-administered with metformin, as metformin plasma concentration may increase. Dose adjustment of metformin may be considered as OCT inhibitors/inducers may alter the efficacy of metformin.
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.
Glibenclamide (Glyburide): Concomitant administration of metformin and glibenclamide produced no changes in metformin pharmacokinetics and pharmacodynamics. Decreases in C_max, blood AUC of glibenclamide were observed, but were highly variable. The clinical significance of this finding was unclear.
Levothyroxine: Levothyroxine may reduce the hypoglycemic effect of metformin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is initiated, changed, or stopped, and metformin dosage adjusted as necessary.
Drugs Affecting Glycemic Control: 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.
Drugs Affecting Renal Function: Drugs that may adversely affect renal function and may increase the risk of lactic acidosis include nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists, aldosterone inhibitors, direct renin inhibitors, diuretics (particularly loop diuretics). When starting or using these drugs in combination with metformin, close monitoring of renal function is required.
Others: The pharmacokinetics of propranolol and ibuprofen were not affected by metformin when co-administered in single-dose interaction studies in healthy volunteers.