RiteMED Metformin hydrochloride

Metformin may act via three mechanisms: It reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis; increases insulin sensitivity in the skeletal muscles and adipocytes, improving peripheral glucose uptake and utilization; delays intestinal glucose absorption.

Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase. It also increases the transport capacity of all types of membrane glucose transporters.

• As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus
• Metformin may be used as monotherapy or in combination with other oral antidiabetic agents or with insulin.

Metformin HCl is slowly and incompletely absorbed from the gastrointestinal tract after oral administration. The absolute bioavailability of metformin HCl tablet under fasting conditions is approximately 50 to 60% with metformin doses of 500 mg to 1,500 mg. Single doses of metformin 500 mg to 1,500 mg show lack of dose proportionality with increasing doses which is due to decreased absorption rather than altered elimination.

Metformin distributes rapidly to peripheral body tissues and fluids. It also appears to distribute slowly into erythrocytes and into a deep tissue compartment. Metformin is negligibly bound to plasma proteins. Steady-state plasma concentrations of metformin are generally <1 mcg/mL and are reached within 24 to 48 hours at usual clinical doses and dosing schedules.

Renal elimination of metformin is via glomerular filtration and secretion by the proximal convoluted tubules as unchanged drug. The principal plasma elimination half-life of metformin is about 6.2 hours with 90% of the total dose being cleared within 24 hours in patients with normal renal function. In the blood, the elimination half-life is about 17.6 hours

• Usual Starting Dose: 500 mg two times a day or 850 mg once a day with meals
• Dosage may be increased in increments of 500 mg weekly or 850 mg every two weeks, up to a total of 2,000 mg per day in divided doses.
• Patients can also be titrated from 500 mg two times a day to 850 mg two times a day after two weeks.
• Maximum Dose: 2,550 mg per day, given in divided doses.
• Doses above 2,000 mg may be better tolerated if given in three divided doses with meals.

Recommended Oral Dose in Children 10 to 16 years Old:

Usual starting dose: 500 mg two times a day or 850 mg once a day with meals

• Dosage may be increased by 500 mg weekly up to a maximum of 2,000 mg per day given in divided doses.
• The efficacy and safety of extended-release or sustained-release metformin in pediatric patients have not been established.