| Composition |
Metformin-SR Tablets contain an oral antihyperglycemic drug used in the management
of type 2 diabetes. Metformin hydrochloride is a member of the biguanide class of oral antihyperglycemics.
Metformin-SR Tablets are designed for once-a-day oral administration and deliver 500 mg or 1000 mg of Metformin hydrochloride. |
| Pharmacodynamics properties |
| Metformin-SR Tablets is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin-SR Tablets decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. 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 plasma insulin levels. |
| Properties |
| Metformin-SR Tablets is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. |
| Therapeutic indications |
Metformin SR Tablets, used as a once per day monotherapy, are indicated as an adjunct to diet and exercise to lower blood glucose. Metformin SR Tablets can be used concomitantly with a sulfonylurea or insulin to improve glycemic control in adults.
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| Side effect |
| These pooled results show that the most frequently reported adverse reactions in the Metformin-SR group were headache, infection, diarrhea, and nausea, diarrhea, rhinitis. Similar incidences of these adverse reactions were seen in the immediate-release metformin group. |
| Contraindication |
METFORMIN-SR is contraindicated in patients with:
1. Renal disease or renal dysfunction
2. Congestive heart failure requiring pharmacologic treatment.
3. Known hypersensitivity to metformin.
4. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. |
| Warnings and precautions |
WARNINGS
Lactic Acidosis:
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin
accumulation during treatment with metformin - SR Tablets; when it occurs, it is fatal in approximately 50% of cases.
PRECAUTIONS
General
Monitoring of renal function – Metformin-SR 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. Metformin-SR discontinued if evidence of renal impairment is present.
Use of concomitant medications that may affect renal function or metformin disposition - Concomitant medication(s) that mayaffect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion, should be used with caution.
Radiologic studies involving the use of intravascular iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials) - Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin. Therefore, in patients in whom any such study is
planned, METFORMIN-SR should be temporarily 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.
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-SR therapy, the drug should be promptly discontinued.
Surgical procedures - METFORMIN-SR therapy should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal.
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-SR .
Impaired hepatic function - Since impaired hepatic function has been associated with some cases of lactic acidosis, METFORMIN-SR should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.
Vitamin B 12 levels - Certain individuals (those with inadequate Vitamin B 12 or calcium intake or absorption) appear to be predisposed to developing subnormal Vitamin B 12 levels. In these patients, routine serum Vitamin B 12 measurements at two- to three-year intervals may be useful. |
| Pregnancy and lactation |
Pregnancy
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women with immediate-release metformin or METFORMIN-SR .
Nursing Mothers
Studies have not been conducted in nursing mothers. Because the potential for hypoglycemia in nursing infants may exist, 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. If METFORMIN-SR is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Pediatric Use
The safety and efficacy of METFORMIN-SR has not been evaluated in pediatric patients.
Geriatric Use
No overall differences in effectiveness or safety were observed between these patients and younger patients. |
| Drug interactions |
Glyburide- co-administration of metformin and glyburide did not result in any changes in either metformin pharmacokinetics or pharmacodynamics.
Furosemide - 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
Nifedipine - metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin, and increased the amount excreted in the urine.
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.
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 METFORMIN-SR , the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving METFORMIN-SR , the patient should be observed closely for hypoglycemia. |
| DOSAGE & ADMINISTRATION |
METFORMIN-SR. Dosage of METFORMIN-SR must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose. The maximum recommended daily dose of METFORMIN-SR Tablets in adults is 2500 mg.
METFORMIN-SR should generally be given once daily with the evening meal.
METFORMIN-SR should be started at a low dose, with gradual dose escalation
The usual starting dose of METFORMIN-SR Tablets is 500 -1000 mg once daily with the evening meal, although 500 mg may be utilized when clinically appropriate. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2500 mg once daily with the evening meal. |
| Overdose |
| Hypoglycemia has not been seen even with ingestion of up to 85 grams of immediate-release metformin, although lactic acidosis has occurred in such circumstances. 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. |
