Gen-Metformin - General Information

A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Gen-Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)


Pharmacology of Gen-Metformin

Gen-Metformin is an antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Gen-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.


Gen-Metformin for patients

Patients should be informed of the potential risks and benefits of GLUMETZA and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters.

The risks of lactic acidosis, its symptoms, and conditions that predispose to its development, as noted in the GLUMETZA sections, should be explained to patients. Patients should be advised to discontinue GLUMETZA immediately and to promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Once a patient is stabilized on any dose level of GLUMETZA, gastrointestinal symptoms, which are common during initiation of metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Patients should be counseled against excessive alcohol intake, either acute or chronic, while receiving GLUMETZA. GLUMETZA(metformin hydrochloride extended-release tablets) alone does not usually cause hypoglycemia, although it may occur when GLUMETZA is used in conjunction with oral sulfonylureas and insulin. When initiating combination therapy, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members.

Patients should be informed that GLUMETZA must be swallowed whole and not crushed or chewed, and that the inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet.


Patient Leaflet

GLUMETZA (Gloo-met-za) (metformin hydrochloride extended-release tablets)

Read this information carefully before you start taking this medicine and each time you refill your prescription. There may be new information. This information does not take the place of your doctor's advice. Ask your doctor or pharmacist if you do not understand some of this information or if you want to know more about this medicine.

What is the most important information I should know about GLUMETZA?


GLUMETZA can cause a rare, but serious condition called lactic acidosis (a buildup of an acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital. Stop taking GLUMETZA and call your doctor right away if you get the following symptoms of lactic acidosis.

· You feel very weak or tired.

· You have unusual (not normal) muscle pain.

· You have trouble breathing.

· You have stomach pain with nausea and vomiting, or diarrhea.

· You feel cold, especially in your arms and legs.

· You feel dizzy or lightheaded.

· You have a slow or irregular heartbeat.

· Your medical condition suddenly changes.

You have a higher chance for getting lactic acidosis with GLUMETZA if you:

· have kidney or liver problems

· have congestive heart failure that requires treatments with medicines

· drink a lot of alcohol (very often or short-term "binge" drinking)

· get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting, or diarrhea. Dehydration can also happen when you sweat a lot with activity or exercise and don't drink enough fluids.

· have certain x-ray tests with injectable dye used

· have surgery

· have a heart attack, severe infection, or a stroke

· are 80 years of age of older and have not had your kidney function tested


GLUMETZA is used along with diet and exercise to improve blood sugar control in adults with type 2 diabetes. GLUMETZA may also be used with another anti-diabetes medicine called a sulfonylurea or with insulin to improve blood sugar levels in adults. GLUMETZA helps control your blood sugar in a number of ways.

These include helping your body respond better to the insulin it makes naturally, decreasing the amount of sugar your liver makes, and decreasing the amount of sugar your intestines absorb. GLUMETZA has not been studied in children under 18 years of age.

Who should not take GLUMETZA?

Do not take GLUMETZA if you:

· have kidney problems

· have heart failure that is treated with medicines

· have a condition called metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin.

· are allergic to GLUMETZA or to any of its ingredients. See the end of this leaflet for a list of ingredients in GLUMETZA.

What should I tell my doctor before taking GLUMETZA?

Tell your doctor about all of your medical conditions including if you:

· have kidney problems

· have liver problems

· have heart problems

· drink a lot of alcohol

· are pregnant or planning to become pregnant. It is not known if GLUMETZA can harm your unborn baby. Talk to your doctor about the best way to control your blood sugar levels while pregnant.

· are breastfeeding. It is not known if GLUMETZA passes into your milk and if it can harm your baby. Talk to your doctor about the best way to feed your baby while taking GLUMETZA.

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. GLUMETZA and some of your other medicines can interact. You may need to have the dose of GLUMETZA or certain other medicines adjusted. Certain other medicines can affect your blood sugar control.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist. Talk to your doctor before you start any new medicine.

How should I take GLUMETZA?

· Take GLUMETZA exactly as prescribed. Your doctor will usually start you on a low dose and increase your dose slowly to control your blood sugar levels. Do not change your dose unless told to do so by your doctor.

· Take GLUMETZA once a day in the evening with food.

· Swallow GLUMETZA tables whole. Never crush or chew GLUMETZA tablets. Tell your doctor if you cannot swallow tablets whole. Your doctor will prescribe a different medicine for you.

· You may see the GLUMETZA tablet shell in your stool. You may also see a soft mass of the GLUMETZA inactive ingredients in your stool. Both of these are normal to see in your stool.

· Stay on your exercise and diet program and test your blood sugar regularly while taking GLUMETZA.

· Your doctor should monitor your diabetes and do blood tests on you from time to time to check your kidneys and your liver.

· If you miss a dose of GLUMETZA resume dosing according to schedule.

· If you take too much GLUMETZA or overdose, call your doctor or poison control center right away.

· You may need to stop GLUMETZA for a short period of time if you:

· are sick with severe vomiting, diarrhea or fever, or if you drink a much lower amount of liquid than normal

· plan to have surgery

· are having an x-ray procedure with injection of dye.

Call your doctor right away for instructions.

What should I avoid while taking GLUMETZA?

Do not drink a lot of alcoholic drinks while taking GLUMETZA. This means you should not binge drink for short periods, and you should not drink a lot of alcohol on a regular basis. Alcohol can increase the chance of getting lactic acidosis.

What are the side effects of GLUMETZA?

GLUMETZA can cause a rare, but serious condition, called lactic acidosis (a buildup of an acid in the blood) that can cause death. See "What is the most important information I should know about GLUMETZA?"

The most common side effects of GLUMETZA include diarrhea, nausea, and upset stomach. These side effects usually go away after you take the medicine for a while. Taking your medicine with the evening meal can help reduce these side effects.

GLUMETZA rarely causes low blood sugar (hypoglycemia) by itself. However, low blood sugar can happen if you do not eat enough, if you drink alcohol, or if you take other medicines to lower blood sugar.

Tell your doctor if you have side effects that bother you, last for more than a few weeks, come back after they have gone away, or start later in therapy. You may need a lower dose or need to stop taking GLUMETZA.

These are not all the side effects with GLUMETZA. For more information, ask you doctor or pharmacist.

How should I store GLUMETZA?

· Store GLUMETZA at room temperature, 59° to 86° F (15° to 30° C).

· Keep GLUMETZA and all medicines out of the reach of children.

General information about GLUMETZA

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use GLUMETZA for a condition for which it was not prescribed. Do not give GLUMETZA to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about GLUMETZA. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about GLUMETZA that is written for health professionals or contact 1-866-BIOVAIL (246-799-8245), option 3. You can also visit for additional information.

What are the ingredients in GLUMETZA?

Active Ingredient: 500 mg or 1000 mg of metformin HCL

Inactive Ingredients: Each 500 mg tablets contain coloring, hypromellose, magnesium stearate, microcrystalline cellulose and polyethylene oxide. Each 1000 mg tablet contains crospovidone, dibutyl sebacate, ethylcellulose, glyceryl behenate, polyvinyl alcohol, polyvinylpyrrolidone, and silicon dioxide. GLUMETZA 500 and 1000 mg tablets both utilize advanced, polymer-based, oral drug delivery systems, which allow delivery of metformin HCL to the upper GI tract.


Gen-Metformin 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, Cmax as well as Tmax 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.


Gen-Metformin 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..


Additional information about Gen-Metformin

Gen-Metformin Indication: For use as an adjunct to diet and exercise to improve glycemic control in adult patients (18 years and older) with type 2 diabetes.
Mechanism Of Action: Gen-Metformin's pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Gen-Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Drug Interactions: Cimetidine Cimetidine increases the effect of metformin
Glucosamine Possible hyperglycemia
Food Interactions: Avoid alcohol.
Take with food.
Generic Name: Metformin
Synonyms: Metformin HCL; metformin hydrochloride
Drug Category: Hypoglycemic Agents
Drug Type: Small Molecule; Approved

Other Brand Names containing Metformin: Apo-Metformin; Fortamet; Gen-Metformin; Glucophage; Glucophage XR; Glycon; Novo-Metformin; Nu-Metformin; Riomet;
Absorption: Absorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Food delays absorption.
Toxicity (Overdose): 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.
Protein Binding: Metformin is negligibly bound to plasma proteins.
Biotransformation: Metformin is not metabolized.
Half Life: 6.2 hours
Dosage Forms of Gen-Metformin: Tablet, extended release Oral
Tablet Oral
Chemical IUPAC Name: 3-(diaminomethylidene)-1,1-dimethylguanidine
Chemical Formula: C4H11N5
Metformin on Wikipedia:
Organisms Affected: Humans and other mammals