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ple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, particularly when accompanied by hypoperfusion and hypoxemia due to unstable or acute failure, 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 patients taking GLUMETZA. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. GLUMETZA treatment should not be initiated in any patient unless measurement of creatinine clearance demonstrates that renal function is not reduced. In addition, GLUMETZA should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, GLUMETZA should generally be avoided in patients with clinical or laboratory evidence of hepatic impairment. Patients should be cautioned against excessive alcohol intake when taking GLUMETZA, because alcohol potentiates the effects of metformin on lactate metabolism. In addition, GLUMETZA should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure necessitating restricted intake of food or fluids. Use of topiramate, a carbonic anhydrase inhibitor, in epilepsy and migraine prophylaxis may frequently cause dose-dependent metabolic acidosis (In controlled trials, 32% and 67% for adjunctive treatment in adults and pediatric patients, respectively, and 15 to 25% for monotherapy of epilepsy, with decrease in serum bicarbonate to less than 20mEq/L; 3% and 11% for adjunctive treatment in adults and pediatric patients, respectively, and 1 to 7% for monotherapy of epilepsy, with decrease in serum bicarbonate to less than 17mEq/L) and may exacerbate the risk of metformin-induced lactic acidosis. (See 7.1 Drug Interactions and 12.5 Clinical Pharmacology) The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis.
Patients should be educated to promptly report these symptoms should they occur. If present, GLUMETZA should be withdrawn until lactic acidosis is ruled out. Serum electrolytes, ketones, blood glucose, blood pH, lactate levels, and blood metformin levels may be useful. Once a patient is stabilized on any dose level of GLUMETZA, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to recur. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease. Levels of fasting venous plasma lactate above the upper limit of normal but less than 5mmol/L in patients taking GLUMETZA 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 wit |
