If GLUMETZA is considered appropriate for a patient already receiving immediate-release metformin, the patient can be switched to GLUMETZA once daily at the same total daily dose, up to 2000mg once daily.

GLUMETZA tablets must be swallowed whole and never split, crushed or chewed. Occasionally, the inactive ingredients of GLUMETZA 500mg may be eliminated in the feces as a soft, hydrated mass, while the 1000mg may leave an insoluble shell that may resemble the original tablet. If a dose of GLUMETZA is missed, patients should be cautioned against taking two doses of 2000mg the same day. Resume dosing as according to prescribing recommendations. (See PATIENT COUNSELING INFORMATION (17))

Patients treated with an insulin secretagogue or insulin

Co-administration of GLUMETZA with an insulin secretagogue (e.g.,sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

3. DOSAGE FORMS AND STRENGTHS
GLUMETZA (metformin hydrochloride extended-release tablets) 500mg are available as blue, film coated, oval-shaped tablets debossed with "GMZ" on one side and "500" on the other side.

GLUMETZA (metformin hydrochloride extended-release tablets) 1000mg are available as white, film coated, oval-shaped tablets with "M1000" on one side.

4. CONTRAINDICATIONS
GLUMETZA is contraindicated in patients with:

Renal impairment (e.g.,serum creatinine levels ≥1.5mg/dL for men, ≥1.4mg/dL for women or abnormal creatinine clearance), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia. (See WARNINGS AND PRECAUTIONS (5))
Known hypersensitivity to metformin hydrochloride.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin.
5. WARNINGS AND PRECAUTIONS
5.1 Lactic Acidosis
Lactic acidosis is a serious, metabolic complication that can occur due to metformin accumulation during treatment with GLUMETZA and 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 concentrations (>5mmol/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 >5μg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is approximately 0.03cases/1000patient-years, with approximately 0.015fatal cases/1000patient-years. In more than 20,000patient-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 impairment, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multi