Metformin STELLA

Metformin STELLA

metformin

Nhà sản xuất:

Stellapharm J.V.

Nhà phân phối:

Khuong Duy
Thông tin kê toa chi tiết tiếng Anh
Contents
Metformin hydrochloride.
Description
Metformin STELLA 500 mg: Each film-coated tablet contains Metformin hydrochloride 500 mg.
Metformin STELLA 850 mg:
Each film-coated tablet contains Metformin hydrochloride 850 mg.
Excipients/Inactive Ingredients:
Povidone K25, magnesium stearate, hypromellose, opadry white 02F28644.
Action
Pharmacotherapeutic Group: Blood glucose lowering drugs, excl. insulins. Biguanides. ATC Code: A10BA02.
Pharmacology: Pharmacodynamics: Metformin is a biguanide antidiabetic. Unlike sulfonylureas, metformin does not stimulate insulin secretion from pancreatic beta cells. It does not have a hypoglycemic effect in nondiabetic subjects. In diabetics, it allows reductions of hyperglycemia without causing hypoglycemic accidents (except in cases of fasting or synergistic association). Metformin lowers both basal (fasting) and postprandial plasma glucose concentration in patients with type II (non-insulin dependent) diabetes mellitus (NIDDM). The peripheral mode of action of metformin is evidenced by increased cellular utilization of glucose, improved binding of insulin to its receptor and probably a post-receptor effect, inhibition of hepatic glucose synthesis and reduction of intestinal absorption of glucose. Independent of its antidiabetic action, metformin has favorable effects on lipoprotein metabolism which are often abnormal in NIDDM patients. In contrast to sulfonylureas, body weight of individuals on metformin therapy tends to remain stable or may even decrease somewhat.
Pharmacokinetics: Metformin hydrochloride is slowly and incompletely absorbed from the gastrointestinal tract; the absolute bioavailability of a single 500 mg dose is reported to be about 50 to 60%, although this is somewhat reduced if taken with food. Once absorbed, plasma protein-binding is negligible and it is excreted unchanged in the urine. The plasma elimination half-life is reported to range from about 2 to 6 hours after oral doses. Metformin hydrochloride is distributed into breast milk in small amounts.
Indications/Uses
Metformin is used for the management of non-insulin-dependent diabetes mellitus (type II) as monotherapy when hyperglycemia cannot be managed on diet alone. Metformin may be used concomitantly with a sulfonylurea when diet and metformin or sulfonylurea alone do not result in adequate glycemic control.
Dosage/Direction for Use
Recommended dose: For patients new to metformin, the usual starting oral dose of metformin is 500 mg once daily. If the patient does not have any gastrointestinal adverse reactions and needs to increase dose, an addition of 500 mg metformin may be given at 1-2 weeks intervals. The dosage of metformin should be individualized on the basis of effectiveness and tolerability and should not exceed the maximum recommended daily dose of 2000 mg metformin.
Adults: Metformin STELLA 500 mg: Initial: 1 tablet twice daily (given with the morning and evening meals). Dosage increases should be made in increments of one tablet daily, once every week, up to a maximum of 5 tablets/day. Doses of up to 4 tablets/day may be given twice daily. If a dose of 5 tablets/day is required, it may be better tolerated 3 times/day (with meals).
Metformin STELLA 850 mg: Initial: 1 tablet once daily (given with the morning meal). Dosage increases should be made in increments of one tablet every other week, given in divided doses, up to a maximum of 3 tablets/day.
The usual maintenance dose is 1 tablet twice daily (with the morning and evening meals). Some patients may be given 1 tablet x 3 times/day (with meals).
Children from 10 years of age and adolescents: Monotherapy and combination with insulin: The usual starting dose is one tablet once daily. After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements. The maximum recommended dose of metformin is 2 g daily, taken as 2 or 3 divided doses.
Elderly patients: The initial and maintenance dosing should be conservative, due to the potential for decreased renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin.
Recommendation for use in patients with renal impairment: Assess renal function prior to initiation of metformin and periodically thereafter.
Metformin is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2.
Initiation of metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.
In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m2, assess the benefit and risk of continuing therapy.
Discontinue metformin if the patient's eGFR later falls below 30 mL/minute/1.73 m2 (see Contraindications, Precautions).
Patients with hepatic impairment: Because of the risk of lactic acidosis, which occurs rarely but may be fatal in approximately 50% of cases, metformin should not be used in patients with renal disease or dysfunction and should be avoided in those with clinical or laboratory evidence of hepatic disease.
Discontinuation for iodinated contrast imaging procedures: Discontinue metformin at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intraarterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable.
Administration: Metformin STELLA 500 mg/Metformin STELLA 850 mg is administered orally with or after meals.
Transfer from other antidiabetic agents: No transition period is generally necessary except when transferring from chlorpropamide. When transferring from chlorpropamide, care should be exercised during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.
Concomitant metformin and oral sulfonylurea therapy: If patients have not responded to 4 weeks of the maximum dose of metformin monotherapy, consideration to a gradual addition of an oral sulfonylurea while continuing metformin at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. In patients who do not respond to 1-3 months of concomitant therapy at the maximum dosage of each oral antidiabetic agent, oral antidiabetic therapy generally should be discontinued and insulin therapy instituted.
Overdosage
Hypoglycaemia has not been observed with ingestions up to 85 g of metformin, although lactic acidosis has occurred in such circumstances.
Metformin is dialyzable with a clearance of up to 170 ml/minute; hemodialysis may be useful for removal of accumulated drug from patient in whom metformin overdosage is suspected.
Contraindications
Patients with a history of hypersensitivity reaction to metformin or any excipients.
Patients with acute catabolic states, infection, trauma, which all should be treated with insulin.
Decreased kidney function in renal disease or renal dysfunction (serum creatinine greater than or equal to 1.5 mg/dL in males, or greater than or equal to 1.4 mg/dL in females) which may also result from conditions such as cardiovascular collapse, acute myocardial infarction, and septicemia.
Severe renal impairment (eGFR below 30 mL/minute/1.73 m2) (see Precautions).
Patients with acute or chronic metabolic acidosis including diabetic ketoacidosis.
Severe hepatic disease, severe cardiovascular disease, severe respiratory disease with hypoxaemia.
Congestive heart failure, cardiovascular collapse, acute myocardial infarction.
Chronic hypoxic lung disease.
Severe infection, septicemia.
In acute symptoms of metabolic decompensation, for instance in cases of infection or gangrene.
In pregnant, patients who are always treated with insulin.
Metformin should be temporarily withheld in patients undergoing radiologic studies involving the parenteral administration of iodinated contrast materials because use of such products may result in acute alteration of renal function.
Gangrene, alcoholism, malnutrition.
Special Precautions
Lactic acidosis: There have been post-marketing cases of metformin-associated lactic acidosis, including fatal cases, hypothermia, hypotension, resistant bradyarrhythmias. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels generally >5 μg/mL.
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high-risk groups are provided in the full Prescribing Information (see Dosage & Administration, Contraindications, Precautions, Interactions and Use in specific populations).
If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin. In patients treated with metformin with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to 170 mL/minute under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery.
Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur, instruct them to discontinue metformin and report these symptoms to their healthcare provider.
For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided as follows: Renal impairment: The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient's renal function include (see Dosage & Administration, Pharmacology under Actions): Before initiating metformin, obtain an eGFR.
Metformin is contraindicated in patients with an eGFR less than 30 mL/minute/1.73 m2 (see Contraindications).
Initiation of metformin is not recommended in patients with eGFR between 30-45 mL/minute/1.73 m2.
Obtain an eGFR at least annually in all patients taking metformin. In patients at increased risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently.
In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m2, assess the benefit and risk of continuing therapy.
Drug interactions: The concomitant use of metformin with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation (see Interactions). Therefore, consider more frequent monitoring of patients.
Age 65 or greater: The risk of metformin-associated lactic acidosis increases with the patient's age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. Assess renal function more frequently in elderly patients.
Radiological studies with contrast: Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis. Stop metformin at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after the imaging procedure, and restart metformin if renal function is stable.
Surgery and other procedures: Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment. Metformin should be temporarily discontinued while patients have restricted food and fluid intake.
Hypoxic states: Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur, discontinue metformin.
Excessive alcohol intake: Alcohol potentiates the effect of metformin on lactate metabolism and this may increase the risk of metformin-associated lactic acidosis. Warn patients against excessive alcohol intake while receiving metformin.
Hepatic impairment: Patients with hepatic impairment have developed metformin-associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels. Therefore, avoid use of metformin in patients with clinical or laboratory evidence of hepatic disease.
Patients should be advised that dietary regulation is the principal consideration in the management of diabetes, and that metformin therapy is used only as an adjunct to, and not a substitute for proper dietary regulation.
The administration of oral antidiabetic drugs has been reported to be associated with increased cardiovascular mortality as compared to the treatment with diet alone or the combination of insulin with diet.
Effects on ability to drive and use machines: Metformin hydrochloride monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.
However, patients should be alerted to the risk of hypoglycaemia when metformin hydrochloride is used in combination with other antidiabetic agents (sulfonylureas, insulin, repaglinide).
Use In Pregnancy & Lactation
Pregnancy: Determination of fetal concentrations of metformin hydrochloride suggest that a partial placental barrier to the drug exists. Since abnormal maternal blood glucose concentrations during pregnancy may be associated with a higher incidence of congenital abnormalities, most experts recommend that insulin be used during pregnancy to maintain optimum control of blood glucose concentration.
Lactation: Metformin hydrochloride is distributed into breastmilk. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. If metformin hydrochloride is discontinued in a nursing mother and dietary therapy is inadequate for glycemic control, insulin therapy should be considered.
Adverse Reactions
The most frequent adverse effects of metformin are gastrointestinal. They are dose related, tend to occur at the onset of therapy, and are often transient.
Common (1/100 ≤ ADR < 1/10): Gastrointestinal: Anorexia, nausea, vomiting, diarrhoea, epigastric fullness, constipation, heartburn.
Dermatologic: Rash, urticaria, photosensitivity.
Metabolic: Decrease vitamin B12 levels.
Less Common (1/1,000 ≤ ADR < 1/100): Hematologic:Blood dyscrasias, aplastic anemia, hemolytic anemia, bone marrow suppression, thrombocytopenia, agranulocytosis.
Metabolic: Lactacidosis.
Drug Interactions
Decreased effect: The drugs which tend to produce hyperglycemia (e.g., diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, isoniazide) may lead to a loss of glycemic control.
Increased effect: Furosemide increased the metformin plasma and blood concentration-max without altering metformin renal clearance in a single dose study.
Increased toxicity: Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) which are eliminated by renal tubular secretion could have the potential for interaction with metformin by competing for common renal tubular transport systems. Cimetidine increases (by 60%) the peak metformin plasma and whole blood concentrations; therefore combination with cimetidine must be avoided.
Storage
Store in a well-closed container, in a dry place. Do not store above 30°C.
Shelf-Life: Metformin STELLA 500 mg: 60 months from the date of manufacturing.
Metformin STELLA 850 mg: 36 months from the date of manufacturing.
MIMS Class
ATC Classification
A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.
Presentation/Packing
Metformin STELLA 500 mg: FC tab 500 mg (white, round-shaped, biconvex, plain on both sides) x 3 x 10's, 6 x 10's. Metformin STELLA 850 mg: FC tab 850 mg (white, oblong, with breaking notch on both sides) x 4 x 15's, 6 x 15's.
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