Mefoglip
Glipizide+Metformin Hydrochloride tablet

Presentation
Mefoglip 250 : Each tablet contains Metformin Hydrochloride BP 250 mg and Glipizide USP 2.5 mg.
Mefoglip 500 : Each tablet contains Metformin Hydrochloride BP 500 mg and Glipizide USP 2.5 mg.
Mefoglip DS : Each tablet contains Metformin Hydrochloride BP 500 mg and Glipizide USP 5 mg

Description
This preparation combines glipizide and metformin hydrochloride, two antihyperglycemic agents with complementary mechanism of action, to improve glycemic control in patients with type 2 diabetes. The mechanism by which glipizide lowers blood glucose during long-term administration has not been clearly established. In human, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 month of treatment.
Metformin hydrochloride is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose and by improving insulin sensitivity increases peripheral glucose uptake and utilization.

Indications and Uses
This preparation (glipizide and metformin HCl tablet) is indicated as initial therapy, as an adjunct to diet and exercise, to improve glycemic control in patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone.
This preparation is indicated as second-line therapy when diet, exercise and initial treatment with a sulfonylurea or metformin do not result in adequate glycemic control in patients with type 2 diabetes.

Contraindications
This preparation 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) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction and septicemia (see warnings and precautions).
Congestive heart failure requiring pharmacologic treatment.
Known hypersensitivity to glipizde or metformin hydrochloride.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

Dosage And Administration
Dosage of this preparation must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glipizide/2000 mg metformin. This preparation should be given with meals and should be initiated at a low dose, with gradual dose escalation as described below in order to avoid hypoglycemia, to reduce GI side effects and to permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient.

This preparation as initial Therapy
For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of this preparation is 2.5 mg/250 mg once a day with meal. For patients whose FPG is 280 to 320 mg/dL, a starting dose of this preparation 2.5 mg/500 mg twice daily should be considered. The efficacy of this preparation (glipizide and metformin HCl tablet) in patients whose FPG exceeds 320 mg/dL has not been established. Dosage increases to achieve adequate glycemic control should be made in increments of one tablet per day every two weeks up to maximum of 10 mg/1000 mg or 10 mg/2000 mg of this preparation per day, given in divided doses. In clinical trials of this preparation as initial therapy, there was no experience with total doses greater than 10 mg/2000 mg per day.

This preparation as Second-Line Therapy
For patients not adequately controlled on either glipizide (or another sulfonylurea) or metformin alone, the recommended starting dose of this preparation is 2.5mg/500 mg or 5mg/500mg twice daily with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of this preparation should not exceed the daily doses of glipizide or metformin already being taken. The daily dose should be titrated in increments of no more that 5 mg/500 mg up to the minimum effective dose (to achieve adequate control of blood glucose) or to a maximum dose of 20 mg/2000 mg per day.
Patients previously treated with combination therapy of glipizide (or another sulfonylurea) plus metformin may be switched to this preparation 2.5 mg/500 mg; the starting dose should not exceed the daily dose of glipizide (or equivalent dose of another sulfonylurea) and merformin already being taken. The decision to switch to the nearest equivalent dose or to titrate should be based on clinical judgement. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of this preparation should be titrated as described above to achieve adequate control of blood glucose.



Precautions
This preparation (glipizide and metformin HCl tablet) is capable of producing hypoglycemia. Therefore, proper patient selection, dosing and instructions are important to avoid potential hypoglycemic episodes. The risk of hypoglycemia is increased when strenuous exercise is not compensated by caloric supplementation or during concomitant use with other glucose-lowering agents or ethanol. Renal insufficiency may cause elevated drug levels of both glipizide and merformin hydrochloride. Hepatic insufficiency may increase drug levels of glipizide and may also diminish gluconeoqenic capacity, both of which increase the risk of hypoglycemic reactions. Elderly, debilitated or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects

Side Effects
Generally this combination is well tolerated. However, few side effects including upper respiratory tract infection, diarrhea, dizziness, hypertension, nausea, vomiting, abdominal pain, headache may occur after administration of this preparation

Use in pregnancy & lactation
There are no adequate and well-controlled studies in pregnant women with this preparation or its individual components.

Commercial Pack
Mefoglip 250 : Each box contains, 5 blister strips of 10 tablets.
Mefoglip 500 : Each box contains, 3 blister strips of 10 tablets.
Mefoglip DS : Each box contains, 3 blister strips of 10 tablets
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