Lactic Acidosis
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.)

Indications
RIOMET (metformin hydrochloride oral solution), as a single therapy, is indicated as an adjunct to diet and exercise to improve blood sugar level control in patients with type 2 diabetes.

RIOMET is indicated in patients 10 years of age and older. RIOMET may be used concomitantly with a sulfonylurea or insulin to improve blood sugar level control in adults (17 years of age and older).

Dosage
Carefully measure your dose with a cup provided in the package. Do not use any other household device for measurement as that might result in incorrect dose.

Your doctor will fix the dose based on your medical condition. You may be directed to take a low dose at first; gradually increasing the dose to lower the chance of side effects such as upset stomach or nausea. Follow your doctor's directions carefully. The usual maximum dose for an adult is 25 milliliters each day.

Use
You are strongly advised to read the Patient Information Leaflet available in the medicine pack before you start using RIOMET and each time you get a refill. Consult your doctor or pharmacist for any questions you might have.

In the event of you being on another anti-diabetic drug, please follow your doctor's directions carefully for stopping/continuing the old drug and starting metformin.

Inform your doctor regarding the change in your condition (e.g., blood sugar levels). It may take up to 2 weeks before the full benefit of this drug takes effect.