Each extended release caplet contains: Metformin HCl 500 mg.
Pharmacology: Metformin HCl is an oral antihyperglycemic drug used in the management of type 2 diabetes mellitus. Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin 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 mellitus or normal subject (except in special circumstances, see PRECAUTIONS) and does not cause hyperinsulinemia. With Metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
FORDICA 500 XR is indicated as an adjunct to diet and exercise or may be used concomitantly with sulfonylurea or insulin to improve glycemic control in patients with type 2 diabetes mellitus.
There is no fixed dosage regimen for the management of hyperglicemia in patient with type 2 diabetes with FORDICA 500 XR or any other pharmacologic agent. Dosage of FORDICA 500 XR must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose of 2,000 mg for FORDICA 500 XR.
FORDICA 500 XR should generally be given once daily with evening meals. FORDICA 500 XR should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.
During treatment initiation and dose titration (see recommended dosing schedule), fasting plasma glucose should be used to determine the therapeutic response to FORDICA 500 XR and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of FORDICA 500 XR, either when used as monotherapy or in combination with sulfonylurea or insulin.
Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure i.e. inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure i.e. loss of an adequate blood glucose lowering response after an initial period of effectiveness. Short term administration of FORDICA 500 XR may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.
Recommended Dosing Schedule: In general, clinically significant responses are not seen at doses below 1,500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms. The usual starting dose of FORDICA 500 XR is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2,000 mg once daily with the evening meal. If glycemic control is not achieved on FORDICA 500 XR 2,000 mg once daily, a trial of FORDICA 500 XR 1,000 mg twice daily should be considered.
Transfer from Other Antidiabetic Therapy: When transferring patients from standard oral hypoglicemic agents other than chlorpropamide to FORDICA 500 XR, no transition period generally is necessary. 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 hypoglicemia.
Concomitant FORDICA 500 XR and Oral Sulfonylurea Therapy: If patients have not responded to four weeks of the maximum dose of FORDICA 500 XR monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing FORDICA 500 XR at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug and drug interaction are currently available only from metformin plus glyburide (glibenclamide).
With concomitant FORDICA 500 XR and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant FORDICA 500 XR and sulfonylurea therapy, the risk of hypoglicemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken.
If patients have not satisfactorily responded to one to three months of concomitant therapy with the maximum dose of FORDICA 500 XR and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without FORDICA 500 XR.
Concomitant FORDICA 500 XR and Insulin Therapy: The current insulin dose should be continued upon initiation of FORDICA 500 XR therapy. FORDICA 500 XR therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of FORDICA 500 XR should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2,000 mg for FORDICA 500 XR. It is recommended that the insulin dose be decreased by 10 % to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and FORDICA 500 XR. Further adjustment should be individualized based on glucose-lowering response.
Specific Patient Populations: FORDICA 500 XR is not recommended for use in pregnancy or for use in pediatric patients. The initial and maintenance dosing of FORDICA 500 XR should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of FORDICA 500 XR.
Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly.
Overdose of Metformin HCl has occured, including ingestion of amounts greater than 50 grams. Lactic acidosis has been reported in approximately 32% of Metformin overdose cases.
FORDICA 500 XR is contraindicated in patients with: Renal disease or renal dysfunction (e.g., as suggested by serum creatinine level 1.5 mg/dL [male], 1.4 mg/dL [female] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia.
Congestive heart failure.
Hypersensitivity to Metformin HCl.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.
Patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials.
Lactic acidosis: Lactic acidosis is rare, but serious, metabolic complication that can occur due to Metformin accumulation during treatment with FORDICA 500 XR. When it occurs, it is fatal in approximately 50% of cases. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).
Lactic acidosis is a medical emergency that must be treated in a hospital setting.
In a patient with lactic acidosis who is taking FORDICA 500 XR, the drug should be discontinued immediately and general supportive measures promptly instituted. Because Metformin HCl is dialyzable (with a 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.
Patient should be informed that FORDICA 500 XR must be swallowed whole and not crushed and chewed that the inactive may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet.
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 FORDICA 500 XR. In patients with advanced age, FORDICA 500 XR should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, particularly those ≥80 years of age, renal function should be monitored regularly and, generally, FORDICA 500 XR should not be titrated to the maximum dose.
Before initiation of FORDICA 500 XR therapy and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and FORDICA 500 XR discontinued if evidence of renal impairment is present.
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 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) scan 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 (see Contraindications). In patients in whom any such study is planned, FORDICA 500 XR should be temporarily discontinued at the time of or prior to the procedure.
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 event occur in patients on FORDICA 500 XR therapy, the drug should be promptly discontinued.
Surgical procedures: FORDICA 500 XR 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 FORDICA 500 XR.
Impaired hepatic function: Since impaired hepatic function has been associated with some cases of lactic acidosis, FORDICA 500 XR should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.
Change in clinical status of patients with previously controlled type 2 diabetes: A patient with type 2 diabetes previously well controlled on FORDICA 500 XR 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 ketons, blood glucose and, if indicated, blood pH, lactate, pyruvate, and Metformin levels. If acidosis of either form occurs, FORDICA 500 XR must be stopped immediately and other appropriate corrective measures initiated.
Hypoglycemia: Hypoglycemia does not occur in patients receiving FORDICA 500 XR 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 and insulin) or ethanol.
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.
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 FORDICA 500 XR and temporarily administer insulin.
INFORMATION FOR PATIENTS: Patients should be informed of the potential risks and benefits of FORDICA 500 XR 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 risk of lactic acidosis, its symptoms, and conditions that predispose to its development, should be explained to patients. Patients should be advised to discontinue FORDICA 500 XR 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 FORDICA 500 XR, 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 FORDICA 500 XR .
FORDICA 500 XR alone does not usually cause hypoglycemia, although may occur when FORDICA 500 XR 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.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Studies in Maturity-Onset Diabetes of the Young (MODY) have not been conducted.
Geriatric Use: 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, FORDICA 500 XR should only be used in patients with normal renal function. Because aging is associated with reduced renal function, FORDICA 500 XR 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 FORDICA 500 XR.
Pregnancy: There are no adequate and well-controlled studies in pregnant women with FORDICA 500 XR. Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day.
Nursing Mothers: 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. 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 FORDICA 500 XR is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Gastrointestinal Tract Disorder: abdominal pain, constipation, distention abdomen, dyspepsia/heartburn, flatulence.
Dizziness, headache.
Upper respiratory tract infection.
Taste disturbance.
Glyburide: The single dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain.
Furosemide: No information is available about the interaction of Metformin and furosemide when coadministered chronically.
Nifedipine: 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. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of FORDICA 500 XR and/or the interfering drug is recomended in patients who are taking cationic medications that are excreted via renal tubular secretory system.
Other: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazide 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 FORDICA 500 XR, the patients should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving FORDICA 500 XR, the patient should be observed closely for hypoglycemia.
Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, cloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.
Store below 25°C and in a dry place.
A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.
Fordica 500 XR caplet 500 mg
10 × 10's (Rp185,000/boks)
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