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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.
