There are two major contraindications to the use of metformin: (1) renal disease or dysfunction and (2) metabolic acidosis.
Current standards state males with serum creatinine levels 1.5 or higher, females with levels 1.4 or higher, and patients of either gender with abnormal creatinine clearance rates should not receive metformin because of its heavy dependence on renal function for elimination.
Patients with acute or chronic metabolic acidosis and patients at high risk for lactic acidosis because of tissue hypoperfusion or hypoxia (e.g., severe dehydration, heart failure, respiratory failure, and chronic alcoholism with severe liver damage) also should not receive this drug when being managed solely by primary care providers.
Lactic acidosis is a rare, but serious, complication that can occur with metformin because of its accumulation during treatment. When it occurs, it is fatal 50% of the time. The risk for lactic acidosis increases in the presence of renal and hepatic dysfunction, making the interaction of these two contraindications more serious than either one alone. Metformin also should not be used for patients with clinical and laboratory evidence of hepatic disease.
Cautious use is suggested with patients over age 80 due to the probability of decreased renal function. Limited data suggest that total plasma clearance is decreased and half-life is prolonged in healthy older adults as compared with healthy young subjects. These data suggest that the change in pharmcokinetics is primarily accounted for by change in renal function. For older adults, creatinine clearance rate should be tested before beginning therapy and at least annually during therapy.
Metform should also be temporarily withheld 48 hours before to 48 hours after undergoing radiological studies that involve an iodine-based contrast medium because such materials may result in altered renal function and have been associated with lactic acidosis in patients receiving metformin. Metform should be reinstituted only after renal function has been reevaluated and found to be normal. It should also be temporarily withheld from patients undergoing surgical procedures in which fluid will be withheld because of the risk for dehydration and hypoperfusion that may result in lactic acidosis. The time frame for withholding the drug is the same.
A decrease in vitamin B12 levels to subnormal without clinical manifestations has been observed in about 7% of patients receiving metformin. This decrease is probably due to interference with vitamin B12 absorption from the intrinsic factor-vitamin B12 complex. Patients with or at risk for anemia associated with altered vitamin B12 utilization should have the disorder treated and under control before beginning metformin therapy. The low levels may be the reason why some studies have found a dementia link with the medication.
Woo, Teri Moser, and Marylou V. Robinson. Pharmacotherapeutics for Advance Practice Nurse Prescribers. F.A. Davis Company, 2016.
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