8.3 Nursing Mothers
Studies in lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers. Thus, the potential for hypoglycemia in nursing infants after Metformin HCl Oral Solution may exist.

8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established. GLUMETZA is not recommended in pediatric patients below the age of 18years.

8.5 Geriatric Use
Clinical studies of GLUMETZA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. (See WARNINGS AND PRECAUTIONS (5))

10. OVERDOSAGE
No cases of overdose were reported during GLUMETZA clinical trials. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen. Should those symptoms persist, lactic acidosis should be excluded.

Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases. (See WARNINGS AND PRECAUTIONS (5.1)) Metformin is dialyzable with a clearance of up to 170mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.

11. DESCRIPTION
GLUMETZA (metformin hydrochloride) extended release tablet is an oral antihyperglycemic medication used in the management of type2 diabetes. Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. The structural formula of metformin hydrochloride (metformin HCl) is as shown:

Metformin HCl is a white to off-white crystalline compound with a molecular formula of C4H11N5•HCl and a molecular weight of 165.63. Metformin HCl is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. GLUMETZA tablets are modified release dosage forms that contain 500mg or 1000mg of metformin HCl. Each 500mg tablet contains coloring, hypromellose, magnesium stearate, microcrystalline cellulose and polyethylene oxide. Each 1000mg tablet contains colloidal silicon dioxide, polyvinyl alcohol, crospovidone, glyceryl behenate, polyacrylate dispersion, hypromellose, talc, polyethylene glycol, eudragit, titanium dioxide, simethicone emulsion, polysorbate and coloring. GLUMETZA 500mg and 1000mg tablets are formulated to gradually release metform