General: 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 Metformin. In patients with advanced age, Metformin 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, Metformin should not be titrated to the maximum dose. Before initiation of Metformin 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 Metformin 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) scans 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.
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 events occur in patients on Metformin, the drug should be promptly discontinued.
Surgical procedures: metformin 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 warmed against excessive alcohol intake, acute or chronic, while receiving metformin.
Impaired hepatic function: Since impaired hepatic function has been associated with some cases of lactic acidosis, metformin should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Measurement of hematologic parameters on an annual basis is adviced 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 year intervals may be useful.
Lactic acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation.