Active ingredient: Metformin - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Hypoglycemic Agents

Dosage Forms

• Extended release tablet (500 mg or 1000 mg)

Brands / Synonyms

Actoplus MET; Actoplus MET XR; Apo-Metformin; Fortamet; Gen-Metformin; Glipizide and Metformin; Glucophage; Glucophage XR; Glucovance; Glyburide and Metformin; Glycon; Janumet; Kombiglyze; Metaglip; Metformin; Metformin Extended-Release; Metformin HCL; metformin hydrochloride ; Novo-Metformin; Nu-Metformin; Prandimet; Riomet

Indications

For use as an adjunct to diet and exercise to improve glycemic control in adult patients (18 years and older) with type 2 diabetes.

Pharmacology

Metformin is an antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and daylong plasma insulin response may actually decrease.

Mechanism of Action

Metformin's pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Absorption

Absorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Food delays absorption.

Toxicity

Acute oral toxicity (LD₅₀): 350 mg/kg [Rabbit]. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen.

Biotrnasformation / Drug Metabolism

Metformin is not metabolized.

Contraindications

GLUMETZA is contraindicated in patients with:

1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels >1.5 mg/dL [males], >1.4 mg/dL [females] or abnormal creatinine clearance), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia .

2. Congestive heart failure requiring pharmacologic treatment.

3. Known hypersensitivity to metformin hydrochloride.

4. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

GLUMETZAshould be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function..

Drug Interactions

(Clinical Evaluation of Drug Interactions Conducted with metformin)

Glyburide - The influence of glyburide on GLUMETZA pharmacokinetics was assessed in a single-dose interaction study in healthy subjects. Co-administration of a single dose of 500 mg GLUMETZA and 5 mg glyburide did not result in any changes in metformin pharmacokinetics as AUC, C_max as well as T_max were unchanged. Changes in pharmacodynamics were not evaluated in this study (see DOSAGE AND ADMINISTRATION: Concomitant GLUMETZA and Oral Sulfonylurea Therapy).

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.

Nifedipine - A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that co-administration of nifedipine increased plasma metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine.

Cationic drugs - Cationic drugs (e.g., 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. Such interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics.

Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of GLUMETZA and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.

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. When such drugs are administered to a patient receiving GLUMETZA, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving GLUMETZA, the patient should be observed closely for hypoglycemia. In healthy volunteers, the pharmacokinetics of metformin and propranolol, and metformin and ibuprofen were not affected when co-administered in single-dose interaction studies. Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.