Lactic acidosis is a rare, but serious, form of metabolic acidosis that can occur if metformin accumulates during treatment; when it occurs, it is fatal in approximately 50% of cases. The onset of lactic acidosis often is subtle, and accompanied only by early nonspecific symptoms such as malaise and myalgia (1—5% of patients), and quickly followed by respiratory distress (dyspnea 1—5%), increasing somnolence, and nonspecific abdominal distress. Lactic acidosis is a medical emergency that must be treated in a hospital setting; metformin should be discontinued immediately and general supportive measures promptly instituted. Prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.[28550] Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 mcg/mL are generally found. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked metabolic acidosis. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years); of nearly 20,000 patients in clinical trials, there were no reports of lactic acidosis.[28550] A nested case-control study of 50,048 patients with type 2 diabetes mellitus demonstrated that during concurrent use of oral diabetes drugs, there were 6 identified cases of lactic acidosis; all of the subjects had relevant co-morbidities known to be risk factors for lactic acidosis.[34580] The incidence of lactic acidosis appears to be no more common in metformin recipients without comorbid conditions than in recipients of other antidiabetic agents.[53018] Risk factors include significant renal insufficiency, the presence of multiple concomitant medical/surgical problems (e.g., liver disease, alcoholism, cardiorespiratory insufficiency or other conditions associated with tissue hypoperfusion or hypoxemia), and exposure to multiple concomitant medications known to increase risks. The risk of lactic acidosis increases with the degree of renal impairment and the patient's age. Lactic acidosis is less likely to occur with metformin than with other biguanide agents (e.g., phenformin), because metformin is not metabolized, does not bind to liver or plasma proteins, and is excreted by active tubular processes. Regular monitoring of renal function and by use of the minimum effective dose of metformin may reduce the risk of this adverse reaction. Patients should be informed to discontinue alogliptin; metformin should symptoms suggestive of lactic acidosis appear and promptly report the symptoms to their physician.[53018]
Lactic acidosis is a rare, but serious, form of metabolic acidosis that can occur if metformin accumulates during treatment; when it occurs, it is fatal in approximately 50% of cases. The onset of lactic acidosis often is subtle, and accompanied only by early nonspecific symptoms such as malaise and myalgia (1—5% of patients), and quickly followed by respiratory distress (dyspnea 1—5%), increasing somnolence, and nonspecific abdominal distress. Lactic acidosis is a medical emergency that must be treated in a hospital setting; metformin should be discontinued immediately and general supportive measures promptly instituted. Prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.[28550] Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 mcg/mL are generally found. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked metabolic acidosis. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years); of nearly 20,000 patients in clinical trials, there were no reports of lactic acidosis.[28550] A nested case-control study of 50,048 patients with type 2 diabetes mellitus demonstrated that during concurrent use of oral diabetes drugs, there were 6 identified cases of lactic acidosis; all of the subjects had relevant co-morbidities known to be risk factors for lactic acidosis.[34580] The incidence of lactic acidosis appears to be no more common in metformin recipients without comorbid conditions than in recipients of other antidiabetic agents.[53018] Risk factors include significant renal insufficiency, the presence of multiple concomitant medical/surgical problems (e.g., liver disease, alcoholism, cardiorespiratory insufficiency or other conditions associated with tissue hypoperfusion or hypoxemia), and exposure to multiple concomitant medications known to increase risks. The risk of lactic acidosis increases with the degree of renal impairment and the patient's age. Lactic acidosis is less likely to occur with metformin than with other biguanide agents (e.g., phenformin), because metformin is not metabolized, does not bind to liver or plasma proteins, and is excreted by active tubular processes. Regular monitoring of renal function and by use of the minimum effective dose of metformin may reduce the risk of this adverse reaction. Patients should be informed to discontinue alogliptin; metformin should symptoms suggestive of lactic acidosis appear and promptly report the symptoms to their physician.[53018]
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