Glucophage/Glucophage XR

Metformin HCl

Glucophage Monotherapy or in combination w/ other oral antidiabetics or insulin in adults. Monotherapy or in combination w/ insulin in childn ≥10 yr & adolescents. Reduction of diabetic complications in overwt type 2 diabetic adult patients treated w/ metformin as 1st-line therapy after diet failure. Glucophage XR Monotherapy or in combination w/ other oral antidiabetics or insulin for type 2 DM in adults, particularly overwt patients when dietary management & exercise alone does not result in adequate glycaemic control. Reduction in the risk or delay of the onset of type 2 DM in adult, overwt patients w/ impaired glucose tolerance &/or impaired fasting glucose who are at high risk for developing overt type 2 DM & not suitable for intensive lifestyle modifications.

Glucophage Adult w/ normal renal function (GFR ≥90 mL/min) Monotherapy & in combination w/ other oral antidiabetics Starting dose: 500 mg or 850 mg bd-tds, may be adjusted after 10-15 days. Max: 3 g daily. In combination w/ insulin Starting dose: 500 mg or 850 mg bd-tds, adjust insulin dosage on the basis of blood glucose measurements. Renal impairment GFR 60-89 mL/min Max total daily dose: 3,000 mg, 45-59 mL/min Max total daily dose: 2,000 mg, 30-44 mL/min Max total daily dose: 1,000 mg. Monotherapy & in combination w/ insulin Childn ≥10 yr & adolescent Starting dose: 500 mg bd, may be adjusted after 10-15 days. Max: 2 g daily. Glucophage XR Adult w/ normal renal function (GFR ≥90 mL/min) Reduction in the risk or delay of the onset of type 2 DM Initially 500 mg once daily, may be adjusted after 10-15 days. Max: 2,000 mg once daily. Monotherapy & in combination w/ other oral antidiabetics 500 mg tab: 500 mg once daily. Dosage may be increased in increments of 500 mg every 10-15 days, up to 2,000 mg once daily. If glycaemic control is not achieved on 2,000 mg once daily, consider 1,000 mg bd, may be switched to standard metformin tab to a max of 3,000 mg daily if glycaemic control is still not achieved. 750 mg tab: Dose should be equiv to the daily dose of metformin tab (ER or IR) up to a max of 1,500 mg, may be adjusted after 10-15 days. Recommended dose: 2 tab once daily. If glycaemic control is not achieved on 2,000 mg once daily, consider 1,000 mg bd, may be switched to standard metformin tab to a max of 3,000 mg daily. 1,000 mg tab: 1 tab once daily. Max: 2 tab daily. If glycaemic control is not achieved on 2,000 mg once daily, consider 1,000 mg bd, may be switched to standard metformin tab to a max of 3,000 mg daily. Transfer from another oral antidiabetic Discontinue the other agent & initiate Glucophage XR 500 mg before switching to 750 mg or 1,000 mg. Combination w/ insulin Starting dose: 500 mg once daily, adjust insulin dosage on the basis of blood glucose measurements. Renal impairment GFR 45-89 mL/min Max total daily dose: 2,000 mg, 30-44 mL/min Max total daily dose: 1,000 mg.

Should be taken with food: Take w/ the evening meal. Swallow whole, do not chew/crush.

Hypersensitivity. Acute metabolic acidosis (eg, lactic acidosis, diabetic ketoacidosis). Diabetic pre-coma. Acute conditions w/ potential to alter renal function (eg, dehydration, severe infection, shock). Disease which may cause tissue hypoxia (eg, decompensated heart failure, resp failure, recent MI, shock). Elective major surgery. Hepatic insufficiency; acute alcohol intoxication, alcoholism. Severe renal failure (GFR <30 mL/min).

Increased risk of lactic acidosis; most often occurs at acute worsening renal function, cardioresp illness or sepsis; excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting & hypoxia-associated conditions. Temporarily discontinue use in case of dehydration. Assess GFR before initiating treatment & regularly thereafter. Regularly monitor cardiac & renal function in patients w/ stable chronic heart failure; metformin is contraindicated in acute & unstable heart failure. Discontinue therapy if conditions characterized by hypoxemia occur. Hypoglycemia. Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy; discontinue metformin prior to or at the time of imaging procedure & not restarted until at least 48 hr after provided that renal function has been re-evaluated & stable. Discontinue therapy 48 hr before elective surgery under general, spinal or peridural anaesth. Continue energy-restricted diet in overwt patients. Regularly perform usual lab tests for diabetes monitoring. Monitor vit B₁₂ serum levels annually. Concomitant use of medicinal products that may cause lactic acidosis. Combination w/ insulin or other oral antidiabetics (eg, sulfonylureas or meglitinides); ethanol. May affect ability to drive or use machines due to risk of hypoglycaemia when used in combination w/ other antidiabetics. Pregnancy; maintain blood glucose levels as close to normal as possible throughout pregnancy. Not recommended to breastfeed during treatment. Childn. Elderly ≥75 yr.

GI disorders (eg, nausea, vomiting, diarrhoea, abdominal pain & appetite loss). Vit B₁₂ deficiency; taste disturbance.

Increased risk of lactic acidosis associated w/ alcohol intoxication particularly in cases of fasting, malnutrition or hepatic impairment. Iodinated contrast agents. Increased risk of lactic acidosis w/ NSAIDs including selective COX-2 inhibitors, ACE inhibitors, AIIA & diuretics especially loop diuretics. Medicinal products w/ intrinsic hyperglycaemic activity (eg, local & systemic glucocorticoids & tetracosactides), β₂-agonists, danazol, chlorpromazine (at high dosages of 100 mg daily), diuretics. Efficacy may be reduced by organic cation transporters (OCT)1 inhibitors (eg, verapamil). GI absorption & efficacy may be increased by OCT1 inducers (eg, rifampicin). Renal elimination may be decreased by OCT2 inhibitors (eg, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole). Efficacy & renal elimination may be altered by both OCT1 & OCT2 inhibitors (eg, crizotinib, olaparib).

Antidiabetic Agents

A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.

POM