Glumet/Glumet-XR Warnings

Warning on Lactic Acidosis: Lactic acidosis is a rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin accumulation during treatment. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure. The incidence of lactic acidosis can be reduced by also assessing other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency, and any condition associated with hypoxia.
Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), reduced blood pH, electrolyte disturbance 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.
Lactic acidosis is usually accompanied by nonspecific symptoms such as acidotic dyspnea, vomiting, abdominal pain with muscle cramps, and/or a general feeling of malaise with severe fatigue. Hypothermia followed by coma, hypotension, and resistant bradyarrhythmias may be seen with marked acidosis. Instruct patients to immediately alert their physicians if these symptoms occur. Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood metformin levels may be useful.
Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin HCl is dialyzable, prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.
Do not use metformin in patients with congestive heart failure receiving drugs such as digoxin and furosemide because of the risk of hypoperfusion and hypoxemia which may lead to lactic acidosis.
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
If metformin-associated lactic acidosis is suspected, immediately discontinue metformin HCl and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.