Forbetes Plus 500/5 Special Precautions

Lactic acidosis: Lactic acidosis is a very rare, but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.
In case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake), Metformin should be temporarily discontinued and contact with a healthcare professional is recommended.
Medical product that can acutely impair renal function (such as antihypertensive diuretics and NSAIDs) should be initiated with caution in Metformin treated patients. Other risk factor for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic acidosis, (see Contraindications and Interactions).
Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptom, the patient should stop taking Metformin and seek immediate attention. Diagnostic laboratory findings are decreased blood pH (<7.35), increased plasma lactate levels (>5 mmol/L) and an increased anion gap and lactate/pyruvate ratio.
The reported incidence of lactic acidosis in patients receiving Metformin hydrochloride is very low (approximately 0.03 cases/1,000 patients-years, with approximately 0.015 fatal cases/1,000 patients-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypofunction often in the setting of multiple concomitant medical surgical problems and multiple concomitant meditation. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypofunction and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patient taking Metformin and by use of the minimum effective dose of Metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. this product treatment should not be initiated in patients 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, this product should be promptly with held in the function may significantly limit the ability to clear lactate, this product should generally by avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking this product since alcohol potentiates the effects of Metformin hydrochloride on lactate metabolism. In addition, this product should be temporary discontinued prior to any intravascular radiocontrast study and for any surgical procedure.
The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such is malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient should be instructed to notify the physician immediately if they occur. This product should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood Metformin levels may be useful. Once a patient is stabilized on any dose level of this product, gastrointestinal symptoms, which are common during initiation or therapy with Metformin, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due lactic acidosis or other serious disease.
Level of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking this product do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. 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 this product, the drug should be discontinued immediately and general supportive measures promptly instituted. Because Metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and removed the accumulated Metformin. Such management often result in prompt reversal of symptoms and recovery.
Impaired hepatic function: Since impaired hepatic function has been associated with some cases of lactic acidosis, this product 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 Metformin 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 ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate, and Metformin levels. If acidosis of either form occurs, this product must be stopped immediately and other appropriate corrective measures initiated.
Hypoglycemia: This product is capable of producing hypoglycemia or hypoglycemic symptoms, therefore, proper patient selection, dosing and instructions are important to avoid potential hypoglycemic episodes. The risk of hypoglycemia is increased when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents or ethanol. Renal or hepatic insufficiency may cause elevated drug level of both Glibenclamide and Metformin hydrochloride and the hepatic insufficiency may also diminish gluconeogenic capacity, both of which increase. the risk of hypoglycemic reactions. 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.
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 this product. In patients with advanced age, this product 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, this product should not be titrated to the maximum dose. Before initiation of this product 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 this product 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 if 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 alternation of renal function and have been associated with lactic acidosis in patients receiving Metformin. Therefore, in patients in whom any such study is planned, this product should be temporarily discontinued at the time of or prior to the procedure, and with-held for 48 hours subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal.
Hypoxic states: Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction, and other condition characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on this product therapy, the drug should be promptly discontinued.
Surgery: This product 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 if Metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute chronic, while receiving this product. Due to its effect on the gluconeogenic capacity of the liver, alcohol may also increase the risk of hypoglycemia.
Impaired hepatic function: Since impaired hepatic function has been associated with some cases of lactic acidosis this product should be avoided in patients with clinical or laboratory evidence of hepatic disease.
Vitamin B12 levels: A decrease to subnormal levels of previously normal serum vitamin B12 without clinical manifestations. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of Metformin or vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on Metformin and any apparent abnormalities should be appropriately investigated and managed.
Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels. In these patients, routine serum vitamin B12 measurements at two-to three years intervals may be useful.
Other precautions: Treatment of patients with G6PD-deficiency with Sulfonylurea agents can lead to haemolytic anaemia. Since Glibenclamide belongs to the chemical class of Sulfonylurea drugs, caution is recommended when using this product is patients with G6PD-deficiency and a non Sulfonylurea alternative may be considered.
This product contains Lactose. Therefore its use is not recommended in patients with rare hereditary problems of Galactose-intolerance, the Lapp lactase deficiency or Glucose-Galactose malabsorption.
Use in the Elderly: Age of 65 years and older has been identified as a risk factor for hypoglycemia in patients treated with Sulfonylureas. Hypoglycemia can be difficult to recognize in the elderly. Starting and maintenance doses of Glibenclamide must be carefully adjusted to reduce the risk hypoglycemia (see Dosage & Administration).