Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with RIOMET; when it occurs, it
is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes
mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. 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 µg/mL are generally found.
The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with
approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic
acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal
hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart
failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and
hypoxemia, 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 RIOMET and by use of the minimum
effective dose of RIOMET. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. RIOMET treatment should
not be initiated in patients >= 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients
are more susceptible to developing lactic acidosis. In addition, RIOMET 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, RIOMET should generally be
avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or
chronic, when taking RIOMET, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, RIOMET should be
temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).
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. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify
the physician immediately if they occur (see also PRECAUTIONS). RIOMET should be withdrawn until the situation is clarified. Serum electrolytes, ketones,
blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of
RIOMET, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. 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 5 mmol/L in patients taking RIOMET 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. (See also PRECAUTIONS.)
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 with lactic acidosis who is taking RIOMET, the drug should be
discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to
170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin.
Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.)
Riomet® is to be used as an
adjunct to diet and exercise to help improve your blood sugar level.
You can especially benefit from Riomet if you have difficulty
swallowing metformin/Glucophage ®* tablets, resort to crushing metformin
tablets, and/or experience true dysphagia with the tablet formulation.
For more prescribing and safety information, refer to the
information section or talk to your local healthcare provider about Riomet®
the liquid metformin.
* Glucophage is a registered trademark of