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Metformin HCl

Pharmacology: Metformin is a biguanide derivative producing an antihyperglycemic effect which can only be observed in man or in the diabetic animal and only when there is insulin secretion. Metformin, at therapeutic doses, does not cause hypoglycemia when used alone in man or in the nondiabetic animal, except when using a near lethal dose. Metformin has no effects on the pancreatic beta cells. The mode of action of metformin is not fully understood. It has been postulated that metformin might potentiate the effect of insulin or that it might enhance the effect of insulin on the peripheral receptor site. This increased sensitivity seems to follow an increase in the number of insulin receptors on cell surface membranes. rx canada pharmacy

Metformin absorption is relatively slow and may extend over about 6 hours. The drug is excreted in urine at high renal clearance rate of about 450 mL/min. The initial elimination of metformin is rapid with a half-life varying between 1.7 and 3 hours. The terminal elimination phase accounting for about 4 to 5% of the absorbed dose is slow with a half-life between 9 and 17 hours. Metformin is not metabolized. Its main sites of concentration are the intestinal mucosa and the salivary glands. The plasma concentration at steady-state ranges about 1 to 2 µg/mL. Certain drugs may potentiate the effects of metformin (see Precautions). rx canada pharmacy


Indications: To control hyperglycemia in metformin responsive, stable, mild, non-ketosis prone, maturity onset type of diabetes (Type II) which cannot be controlled by proper dietary management, exercise and weight reduction or when insulin therapy is not appropriate. rx canada pharmacy

Metformin can be of value for the treatment of obese diabetic patients. rx canada pharmacy

Contraindications: Unstable and/or insulin-dependent (Type I) diabetes mellitus. rx canada pharmacy

Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma. Diabetic ketoacidosis should be treated with insulin. rx canada pharmacy

In patients with a history of lactic acidosis, irrespective of precipitating factors. rx canada pharmacy

In the presence of renal impairment or when renal function is not known, and also in patients with serum creatinine levels above the upper limit of normal range. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ³ 136 µmol/L [males], ³ 124 µmol/L [females] or abnormal creatinine clearance) which may result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see also Warnings and Precautions). Congestive heart failure requiring pharmacologic treatment. rx canada pharmacy

In excessive alcohol intake, acute or chronic. rx canada pharmacy

In patients suffering from severe hepatic dysfunction, since severe hepatic dysfunction has been associated with some cases of lactic acidosis, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. rx canada pharmacy

Metformin should 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 (see Warnings and Precautions). rx canada pharmacy

In cases of cardiovascular collapse and in disease states associated with hypoxemia such as cardiorespiratory insufficiency, which are often associated with hyperlactacidemia. rx canada pharmacy

During stress conditions, such as severe infections, trauma or surgery and the recovery phase thereafter. rx canada pharmacy

In patients suffering from severe dehydration. rx canada pharmacy

Known hypersensitivity or allergy to metformin or any of the excipients. rx canada pharmacy

Pregnancy: During pregnancy. rx canada pharmacy


Warnings: Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that occurs due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 µg/mL are generally found. rx canada pharmacy

The reported incidence of lactic acidosis in patients receiving metformin is very low (approximately 0.03 cases/1 000 patient-years, with approximately 0.015 fatal cases/1 000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin treatment should not be initiated in patients ³80 years of age, unless measurement of creatinine clearance demonstrates that renal function is not reduced, as the patients are more susceptible to developing lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking metformin, since alcohol intake potentiates the effect of metformin on lactate metabolism. In addition, metformin should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see Precautions). The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension and resistance bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see Precautions). Metformin should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of metformin, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity or technical problems in sample handling. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). rx canada pharmacy

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin is dialyzable (with clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery (see Contraindications and Precautions). rx canada pharmacy

If acidosis of any kind develops, metformin should be discontinued immediately. rx canada pharmacy

Increased Risk of Cardiovascular Mortality: The administration of oral antidiabetic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 1 027 patients who were randomly assigned to 1 of the 5 treatment groups. rx canada pharmacy

The UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 g/day) or diet plus a fixed dose of phenformin (100 mg/day), had a rate of cardiovascular mortality approximately 2.5 times that of patients treated with diet alone, resulting in discontinuation of both these treatments in the UGDP study. Total mortality was increased in both the tolbutamide-and phenformin-treated groups and this increase was statistically significant in the phenformin-treated group. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and benefits of metformin and alternative modes of therapy. rx canada pharmacy

Although only one drug in the sulfonylurea category (tolbutamide) and one in the biguanide category (phenformin) were included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other related antidiabetic drugs, in view of the similarities in mode of action and chemical structure among the drugs in each category. rx canada pharmacy

The use of metformin will not prevent the development of complications peculiar to diabetes mellitus. rx canada pharmacy

Use of metformin must be considered as treatment in addition to proper dietary regimen and not as a substitute for diet. rx canada pharmacy

Care should be taken to ensure that metformin is not given when a contraindication exists. rx canada pharmacy

If during metformin therapy the patient develops acute intercurrent disease such as: clinically significant hepatic dysfunction, cardiovascular collapse, congestive heart failure, acute myocardial infarction, or other conditions complicated by hypoxemia, the drug should be discontinued. rx canada pharmacy

Radiologic studies involving the use of iodinated contrast materials (e.g., i.v. urogram, i.v. cholangiography, angiography and scans with contrast materials): Intravascular contrast studies with iodinated materials can lead to acute renal failure and have been associated with lactic acidosis in patients receiving metformin (see Contraindications). Therefore, in patients in whom any such study is planned, metformin should be discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal. rx canada pharmacy

Precautions: Patient Selection and Follow-up: Careful selection of patients is important. It is imperative that there be rigid attention to diet and careful adjustment of dosage. When metformin is combined with a sulfonylurea, instruct the patient on hypoglycemic reactions and their control. Regular through follow-up examinations are necessary (see Warnings). rx canada pharmacy

If vomiting occurs, withdraw drug temporarily, exclude lactic acidosis, then resume dosage cautiously (see Adverse Effects). rx canada pharmacy

Particular attention should be paid to short-range and long-range complications which are peculiar to diabetes. Periodic cardiovascular, ophthalmic, hematological, hepatic and renal assessments are advisable (see Warnings). rx canada pharmacy

Monitoring of Renal Function: Metformin is known to be substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive metformin. In patients with advanced age, metformin should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, renal function should be monitored regularly and generally, metformin should not be titrated to the maximum dose (see Dosage). rx canada pharmacy

Before initiation of metformin therapy and every 6 months while on metformin therapy, renal function should be assessed and verified as being within normal range. rx canada pharmacy

In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and metformin discontinued if evidence of renal impairment is present. rx canada pharmacy

Use of Concomitant Medications That May Affect Renal Function or Metformin Disposition: Concomitant medication(s) that may affect renal function or result in significant hemodynamic change or may interfere with disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion (see Drug Interactions), should be used with caution. rx canada pharmacy

Hypoxic States: Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on metformin therapy, the drug should be promptly discontinued. rx canada pharmacy

Surgical Procedures: Metformin therapy should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids). Metformin should be discontinued 2 days before surgical intervention and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal. rx canada pharmacy

Alcohol Intake: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving metformin. rx canada pharmacy

Impaired Hepatic Function: Since impaired hepatic function has been associated with some cases of lactic acidosis, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. rx canada pharmacy

Vitamin B ₁₂ Levels: Impairment of vitamin B ₁₂ and folic acid absorption has been reported in some patients. Therefore, measurements of serum vitamin B ₁₂ and folic acid are advisable at least every 1 to 2 years in patients on long-term treatment with metformin. rx canada pharmacy

A decrease to subnormal levels of previously normal serum vitamin B ₁₂ levels, without clinical manifestations, is observed in approximately 7% of patients receiving metformin in controlled clinical trials of 28 weeks duration. Such decrease, possibly due to interference with B ₁₂ absorption from B ₁₂-intrinsic factor complex is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or vitamin B ₁₂ supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on metformin and any apparent abnormalities should be appropriately investigated and managed (see Laboratory Tests). Certain individuals (those with inadequate vitamin B ₁₂ or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B ₁₂ levels. rx canada pharmacy

Change in Clinical Status of Previously Controlled Diabetic: A diabetic patient previously well controlled on metformin who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate and metformin levels. If acidosis of either form occurs, metformin must be stopped immediately and appropriate corrective measures initiated (see Warnings). rx canada pharmacy

Hypoglycemia: Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose lowering agents (such as sulfonylureas) or ethanol. rx canada pharmacy

Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. rx canada pharmacy

Loss of Control of Blood Glucose: When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold metformin and temporarily administer insulin. Metformin may be reinstituted after the acute episode is resolved. rx canada pharmacy

The effectiveness of oral antidiabetic drugs in lowering blood glucose to a targeted level decreases in many patients over a period of time. This phenomenon, which may be due to progression of the underlying disease or to diminished responsiveness to the drug, is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective during initial therapy. Should secondary failure occur with metformin or sulfonylurea monotherapy, combined therapy with metformin and sulfonylurea may result in a response. Should secondary failure occur with combined metformin/sulfonylurea therapy, it may be necessary to initiate insulin therapy. rx canada pharmacy

Laboratory Tests: Response to all diabetic therapies should be monitored by periodic measurements of fasting blood glucose and glycosylated hemoglobin levels, with a goal of decreasing these levels toward the normal range. During initial dose titration, fasting glucose can be used to determine the therapeutic response. Thereafter, both glucose and glycosylated hemoglobin should be monitored. Measurements of glycosylated hemoglobin may be especially useful for evaluating long-term control (see Dosage). rx canada pharmacy

Initial and periodic monitoring of hematologic parameters (e.g., hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with metformin therapy, if this is suspected, vitamin B ₁₂ deficiency should be excluded. rx canada pharmacy

Pregnancy: Safety in pregnant women has not been established. Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day, or about 2 times the maximum recommended human daily dose on a body surface area basis. Determination of fetal concentrations demonstrated a partial placental barrier to metformin. Because animal reproduction studies are not always predictive of human response, any decision to use this drug should be balanced against the benefits and risks. rx canada pharmacy

Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, there is a consensus among experts that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. rx canada pharmacy

Lactation: Studies in lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers, but caution should be exercised in such patients, and a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. rx canada pharmacy

Children: Safety and effectiveness in pediatric patients have not been established. rx canada pharmacy

Geriatrics: Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and younger patients. Metformin is known to be substantially excreted by the kidney and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, it should only be used in patients with normal renal function (see Contraindications and Warnings). Because aging is associated with reduced renal function, metformin should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin. rx canada pharmacy

Drug Interactions : Certain drugs may potentiate the effect of metformin, particularly sulfonylurea type of drugs in the treatment of diabetes. The simultaneous administration of these two types of drugs could produce a hypoglycemic reaction, especially if they are given in patients already receiving other drugs which, themselves, can potentiate the effect of sulfonylureas. These drugs can be: long-acting sulfonamides, tuberculostatics, phenylbutazone, clofibrate, MAO inhibitors, salicylates, probenecid and propranolol. rx canada pharmacy

In healthy volunteers, the pharmacokinetics of propranolol and ibuprofen were not affected by metformin when coadministered in single-dose interaction studies. rx canada pharmacy

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 sulfonylureas, which are extensively bound to serum proteins. rx canada pharmacy

Glyburide: In a single-dose interaction study in NIDDM subjects, coadministration of metformin and glyburide did not result in any changes in either metformin pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and C _max were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamics effects, makes the clinical significance of this interaction uncertain. rx canada pharmacy

Furosemide: A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the metformin plasma and blood C _max by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, the C _max 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 coadministered chronically. rx canada pharmacy

Nifedipine: A single-dose, metformin-nifedipine drug interaction study in healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin C _max and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. T _max and half-life were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine. rx canada pharmacy

Cationic Drugs: Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and 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 an interaction has been observed between metformin and oral cimetidine 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 was observed. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Therefore, careful patient monitoring and dose adjustment of metformin or the interfering drug is recommended in patients who are taking cationic medications that are excreted via renal tubular secretion. rx canada pharmacy

Other: Other drugs tend to produce hyperglycemia and may lead to a loss of blood sugar control. These include thiazide and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, estrogen plus progestogen, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to patients receiving metformin, the patient should be closely observed to maintain adequate glycemic control. rx canada pharmacy

Elimination rate of the anticoagulant phenprocoumon has been reported to be increased by 20% when used concurrently with metformin. Therefore, patients receiving phenprocoumon or other antivitamin K anticoagulants should be monitored carefully when both types of drugs are used simultaneously. In such cases, an important increase of prothrombin time may occur upon cessation of metformin therapy, with an increased risk of hemorrhage. rx canada pharmacy

Note: When used as indicated, there has not been a single case of lactic acidosis in Canada. The reported incidence of lactic acidosis in patients receiving metformin is very low (approximately 0.03 cases/1 000 patient/years with approximately 0.015 fatal cases/1 000 patient/years). Metformin should be immediately discontinued in the presence of acidosis. rx canada pharmacy

Physicians should instruct their patients to recognize the symptoms which could signal the onset of lactic acidosis (see Warnings). rx canada pharmacy

Adverse Effects: Lactic Acidosis: (See Warnings, Precautions, and Overdose). rx canada pharmacy

Gastrointestinal: Gastrointestinal symptoms (diarrhea, nausea, vomiting, abdominal bloating, flatulence, and anorexia) are the most common reactions to metformin and are approximately 30% more frequent in patients on metformin monotherapy than in placebo-treated patients, particularly during initiation of metformin therapy. These symptoms are generally transient and resolve spontaneously during continued treatment. Occasionally, temporary dose reduction may be useful. rx canada pharmacy

Because gastrointestinal symptoms during therapy initiation appear to be dose-related, they may be decreased by gradual dose escalation and by having patients take metformin with meals (see Dosage). rx canada pharmacy

Because significant diarrhea and/or vomiting can cause dehydration and prerenal azotemia, metformin should be temporarily discontinued, under such circumstances. rx canada pharmacy

For patients who have been stabilized on metformin, nonspecific gastrointestinal symptoms should not be attributed to therapy unless intercurrent illness or lactic acidosis have been excluded. rx canada pharmacy

Special Senses: During initiation of metformin therapy, approximately 3% of patients may complain of an unpleasant or metallic taste, which usually resolves spontaneously. rx canada pharmacy

Dermatologic: The incidence of rash/dermatitis in controlled clinical trials was comparable to placebo for metformin monotherapy and to sulfonylurea for metformin/sulfonylurea therapy. rx canada pharmacy

Hematologic: During controlled clinical trials of 29 weeks duration, approximately 9% of patients on metformin monotherapy and 6% of patients on metformin/sulfonylurea therapy developed asymptomatic subnormal serum vitamin B ₁₂ levels; serum folic acid levels did not decrease significantly. However, only 5 cases of megaloblastic anemia have been reported with metformin administration (none during U.S. clinical studies) and no increased incidence of neuropathy has been observed. Therefore, serum vitamin B ₁₂ levels should be appropriately monitored or periodic parenteral B ₁₂ supplementation considered (see also Precautions). rx canada pharmacy

Overdose: Symptoms and Treatment: Available information concerning treatment of a massive overdosage of metformin is very limited. 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. Should those symptoms persist, lactic acidosis should be excluded. The drug should be discontinued and proper supportive therapy instituted. rx canada pharmacy

Hypoglycemia has not been seen even with ingestion of up to 85 g of metformin, although lactic acidosis has occurred in such circumstances (see Warnings). Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected. rx canada pharmacy


Dosage: In diabetic patients, individual determination of the minimum dose that will lower blood glucose adequately should be made. rx canada pharmacy

In patients where on initial trial the maximal recommended dose fails to lower the blood glucose adequately, the drug should be discontinued. Deterioration of the patient's condition can occur during the treatment of diabetes. It is advisable to ascertain the contribution of the drug in the control of blood glucose by discontinuing the medication semi-annually or at least annually with careful monitoring of the patient. If the need for the drug is not evident, the drug should not be resumed. In some diabetic subjects, short-term administration of the drug may be sufficient during periods of transient loss of blood sugar control. rx canada pharmacy

The usual dose is 500 mg 3 or 4 times a day, or 850 mg 2 or 3 times a day. Maximal dose should not exceed 2.55 g a day. To minimize gastric intolerance such as nausea and vomiting, metformin should be taken with food whenever possible. rx canada pharmacy


Supplied: 500 mg: Each white, round, biconvex tablet, secant on one face and debossed with HMR on the other, contains: metformin HCl 500 mg. Nonmedicinal ingredients: magnesium stearate and povidone. Bottles of 100 and 500. rx canada pharmacy

850 mg: Each white, oblong tablet, debossed with HMR on one face and 850 on the other, contains: metformin 850 mg. Nonmedicinal ingredients: magnesium stearate and povidone. Bottles of 100. rx canada pharmacy

Store at 15 to 30°C in well-closed containers.

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