Uses of Metarin Plus: - Type 2 diabetes mellitus Type 2 DM It is contraindicated in patients with renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels .1.5 mg/dl (males), 1.4 mg/dl (females), or abnormal creatinine clearance), acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma & known hypersensitivity to rosiglitazone maleate or metformin HCl.

How to use Metformin Hydrochloride + Rosiglitazone: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Metformin Hydrochloride + Rosiglitazone is to be taken with food. Adult Dose: Oral Type 2 Diabetes The recommended starting dose of Rosiglitazone/Metformin is 2 mg/500 mg once or twice daily. HbA1c >11% or fasting plasma glucose (FPG) >270 mg/dL, a starting dose of 500 mg/2 mg PO BID may be considered May titrate by increments of 500 mg/2 mg at 2-week intervals, not to exceed 2000 mg/8 mg per day For patients inadequately controlled on Metformin monotherapy, the usual starting dose is 4 mg Rosiglitazone (daily dose) plus the dose of Metformin already being taken. For patients inadequately controlled on Rosiglitazone monotherapy, the usual starting dose is 1000 mg Metformin (daily dose) plus the dose of Rosiglitazone already being taken. Child Dose: Safety and efficacy not established Renal Dose: Renal impairment Obtain eGFR before starting metformin eGFR <30 mL/min/1.73 m²: Contraindicated eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly) If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug

Additive effect w/ sulfonylureas. Thiazide diuretics, corticosteroids, phenothiazines, OC, sympathomimetics, niacin, Ca channel blockers and isoniazid may exacerbate loss of glycaemic control. ACE inhibitors may reduce fasting blood glucose concentrations. May increase serum level w/ cimetidine. Potentially Fatal: Concurrent use w/ iodinated contrast agents may increase the risk of metformin-induced lactic acidosis.

It is contraindicated in patients with renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels .1.5 mg/dl (males), 1.4 mg/dl (females), or abnormal creatinine clearance), acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma & known hypersensitivity to rosiglitazone maleate or metformin HCl.

Common - Nausea - Loss of appetite - Taste change - Stomach pain - Diarrhea - Edema (swelling) - Weight gain - Bone fracture - Blurred vision - Respiratory tract infection >10% Edema (6% to 25% ),Upper respiratory infections (16-20%),Diarrhea (12.7% to 14%),Hypoglycemia (12% ) 1-10% Anemia (4% to 7%),Fatigue (6%),Headache (6%),Sinusitis (6%),Arthralgia (5%),Back pain (5%),Viral infection (5%) Frequency Not Defined (serious) Angioedema (rare ),Congestive heart failure,Death, from cardiovascular causes,Stevens-Johnson syndrome (rare ),Lactic acidosis (rare ),Hepatotoxicity (rare),Anaphylaxis (rare),Diabetic macular edema,Pleural effusion,Pulmonary edema

Precaution: Rosiglitazone: should not be used in patients with type 1 diabetes. This should be used with caution in patients with edema. Dose-related weight gain was seen with rosiglitazone alone and rosiglitazone together with other hypoglycemic agents. Metformin: Monitoring of renal function: Patients with serum creatinine levels above the upper limit of normal should not receive this tablet. In patients with advanced age, the dose should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. Lactation: not known if crosses into breast milk, avoid

Rosiglitazone: Lowers glucose by improving target cell response to insulin without increasing pancreatic cell secretion; activates nuclear peroxisome proliferator-activated receptor gamma, which influences the production of gene products involved in glucose and lipid metabolism. Metformin: Biguanide; acts by decreasing endogenous hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization; improves glucose tolerance and lowers both basal and postprandial plasma glucose .