Glumeform 500
GLUMEFORM 500
COMPOSITION:
Metformin hydrochloride ......................................................... 500 mg
Excipients q.s ......................................................................... 1 tablet
(Avicel, PVP K30, magnesium stearate, sepifilm, pregelatinized starch).
DOSAGE FORM: Film coated tablet.
PRESENTATION: Box of 10 blisters x 10 film coated tablets.
PHARMACODYNAMICS: Glumeform is an antihyperglycemic agent including active ingredient - Metformin. It belongs to biguanide class. Metformin improves glucose tolerance in patients with type 2 diabetes, lowering both fasting and postprandial plasma glucose. Its mechanisms of action are explained as follows: metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, enhances cellular glucose utilization, improves insulin binding to receptors, and stimulates glucose disintegration via anaerobic pathway. Glumeform reduces hyperglycemia in patients suffering from diabetes, but does not produce hypoglycemia (except for cases of starvation or combination with other synergism drugs). The drug also does not produce hypoglycemia in normal subjects. Glumeform not only has antihyperglycemic effect but also usefully influences lipemia components in patients with type 2 diabetes. The drug diminishes the concentration of triglyceride, total cholesterol and LDL cholesterol. The activities of increased fibrinogenolysis and decreased platelet aggregation are recorded in diabetic patients after treatment with metformin.
PHARMACOKINETICS: Metformin is slowly and incompletely absorbed in the gastro-intestinal tract. Its bioavailability is about 50 - 60%. Food prevents the absorptive level and speed of metformin. Metformin is inappreciably bound to plasma proteins. The drug is mainly excreted by the kidney as non-metabolism form. It has plasma half-life of about 1.5 - 4.5 hrs.
INDICATIONS: For the treatment of type 2 (non-insulin dependent) diabetes mellitus, especially for obese patients who put on an effectless diet.
CONTRAINDICATIONS:
Hypersensitivity to any of the components. Acute catabolism state, infections, trauma. Severe liver disease, severe cardiovascular disease, serious respiratory diseases associated with hypoxia. Congestive heart failure, cardiovascular collapse, acute myocardial infarction. Severe infections, septicemia. Necrosis, alcoholism, malnutrition. 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.
Severe renal failure (eGFR below 30 mL/min/1.73m2) [see Warnings and precautions].
Known hypersensitivity to metformin.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis
WARNINGS AND PRECAUTIONS:
Reports show that use of antihyperglycemic agents increase cardiovascular death rate compared with treated by diet or combination of insulin and diet.
Lactic acidosis:
Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmia. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and 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 anyhydrase 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 and Administration, Contraindications, Warnings and 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 metformin treated patients 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 below:
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 and Administration, Clinical Pharmacology]:
- Before initiating metformin, obtain an estimated glomerular filtration rate (eGFR).
- Metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 [see Contraindiations].
- Initiation of metformin is not recommended in patients with eGFR between 30 - 45 mL/min/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/min/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 Drug 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/min/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. Re-evaluate 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 with cases of 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.
PREGNANCY AND LACTATION:
Metformin is not recommended for use in pregnancy. 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.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINE:
Hypoglycemia can occur in patients receiving metformin and other antihyperglycemic drugs.
INTERACTIONS:
Certain drugs may lead to loss of glycemic control of metformin. These drugs include other diuretics, corticosteroids, phenothiazines, oral contraceptives, estrogens, phenytoin, nicotinic acid, calcium channel blocking drugs, isoniazid, and sympathomimetics.
Cationic drugs (including amiloride, digoxin, morphine, ranitidine, trimethoprim, vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems.
Cimetidin shows a 60% increase in peak metformin plasma; therefore, metformin should not be combined with cimetidin.
ADVERSE EFFECTS:
Frequently: Gastrointestinal disorders (including anorexia, nausea, vomiting, diarrhea, epigastric pain, constipation, heartburn), rash, urticaria, decreased vitamin B12 concentration.
Infrequently: dysplasia of blood, aplastic anemia, hemolytic anemia, marrow impairment, thrombocytopenia, agranulocytosis, lactic acidosis.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE:
Hypoglycemia has not been seen even with ingestion of up to 85 grams of metformin, although lactic acidosis has occurred in such circumstances. Metformin is dialyzable with a clearance of up to 170 mL/min. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.
DOSAGE & ADMINISTRATION:
Recommended dosage: The starting dose of metformin in patients who are not currently taking metformin is 500 mg orally, once daily. Increase the dose in 500 mg increments every 1-2 weeks if a higher dose of metformin is needed and there are no gastrointestinal adverse reactions. The dosage of metformin must be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended daily dose of 2000 mg.
Adults: The starting dose is 1 tablet twice a day, given with breakfast and lunch. If necessary, dosage increases should be made in increments of 1 tablet 3 times a day.
The maintenance dose is 1 tablet 2 to 3 times a day, given with meals.
Elderly patients: The initial and maintenance dosing of metformin should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Generally, elderly patients should not be titrated to the maximum dose of metformin.
Transfer from other antidiabetic therapy:
When transferring patients from chlorpropamide, care should be exercised during the first two 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 four weeks of the maximum dose of metformin monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin at the maximum dose. If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of metformin and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin.
Patients with hepatic damages:
Metformin should not also be avoided by patients with clinical and laboratory hepatic disease.
Recommendations for use in 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/min/1.73 m2.
Initiation of metformin in patients with an eGFR between 30-45 mL/min/1.73 m2 is not recommended.
In patients taking metformin whose eGFR later falls below 45 mL/min/1.73 m2, assess the benefit risk of continuing therapy.
Discontinue metformin if the patient's eGFR later falls below 30 mL/min/1.73 m2 [see Contraindications, Warnings and Precautions].
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/min/1.73 m2; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable [see Warnings and Precautions].
Or as prescribed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
This drug is for prescriptions only.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer's.