INDICATIONS AND USAGE Glipizide and metformin hydrochloride tablets USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Mechanism of Action Glipizide and metformin hydrochloride tablets combine glipizide and metformin hydrochloride, 2 antihyperglycemic agents with complementary mechanisms of action, to improve glycemic control in patients with type 2 diabetes. Glipizide appears to lower blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs. The mechanism by which glipizide lowers blood glucose during long-term administration has not been clearly established. In man, 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 months 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 improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
DOSAGE AND ADMINISTRATION General Considerations Dosage of glipizide and metformin hydrochloride tablets 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. Glipizide and metformin hydrochloride tablets 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 (largely due to glipizide), reduce GI side effects (largely due to metformin), and permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient. With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to glipizide and metformin hydrochloride tablets and to identify the minimum effective dose for the patient. Thereafter, HbA 1c should be measured at intervals of approximately 3 months to assess the effectiveness of therapy. The therapeutic goal in all patients with type 2 diabetes is to decrease FPG, PPG, and HbA 1c to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA 1c , which is a better indicator of long-term glycemic control than FPG alone. No studies have been performed specifically examining the safety and efficacy of switching to glipizide and metformin hydrochloride tablet therapy in patients taking concomitant glipizide (or other sulfonylurea) plus metformin. Changes in glycemic control may occur in such patients, with either hyperglycemia or hypoglycemia possible. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring. When colesevelam is coadministered with glipizide ER, maximum plasma concentration and total exposure to glipizide is reduced. Therefore, glipizide and metformin hydrochloride tablets should be administered at least 4 hours prior to colesevelam. Glipizide…
Always consult a registered doctor before taking any medicine. This information is for general knowledge only.
ADVERSE REACTIONS Glipizide and Metformin Hydrochloride Tablets In a double-blind 24-week clinical trial involving glipizide and metformin hydrochloride tablets as initial therapy, a total of 172 patients received glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, 173 received glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg, 170 received glipizide, and 177 received metformin. The most common clinical adverse events in these treatment groups are listed in Table 4 . Table 4: Clinical Adverse Events > 5% in any Treatment Group, by Primary Term, in Initial Therapy Study Adverse Event Number (%) of Patients Glipizide 5 mg Tablets N = 170 Metformin 500 mg Tablets N = 177 Glipizide and Metformin Hydrochloride Tablets, 2.5 mg/250 mg N = 172 Glipizide and Metformin Hydrochloride Tablets, 2.5 mg/500 mg N = 173 Upper respiratory infection 12 (7.1) 15 (8.5) 17 (9.9) 14 (8.1) Diarrhea 8 (4.7) 15 (8.5) 4 (2.3) 9 (5.2) Dizziness 9 (5.3) 2 (1.1) 3 (1.7) 9 (5.2) Hypertension 17 (10.0) 10 (5.6) 5 (2.9) 6 (3.5) Nausea/vomiting 6 (3.5) 9 (5.1) 1 (0.6) 3 (1.7) In a double-blind 18-week clinical trial involving glipizide and metformin hydrochloride tablets as second-line therapy, a total of 87 patients received glipizide and metformin hydrochloride tablets, 84 received glipizide, and 75 received metformin. The most common clinical adverse events in this clinical trial are listed in Table 5 . Table 5: Clinical Adverse Events > 5% in any Treatment Group, by Primary Term, in Second-Line Therapy Study Number (%) of Patients Adverse Event Glipizide 5 mg Tablets The dose of glipizide was fixed at 30 mg daily; doses of metformin and glipizide and metformin hydrochloride tablets were titrated. N = 84 Metformin 500 mg Tablets N = 75 Glipizide and Metformin Hydrochloride Tablets, 5 mg/500 mg N = 87 Diarrhea 11 (13.1) 13 (17.3) 16 (18.4) Headache 5 (6.0) 4 (5.3) 11 (12.6) Upper respiratory infection 11 (13.1) 8 (10.7) 9 (10.3) Musculoskeletal pain 6 (7.1) 5 (6.7) 7 (8.0)…
CONTRAINDICATIONS Glipizide and metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) (see WARNINGS and PRECAUTIONS ). Known hypersensitivity to glipizide or metformin hydrochloride. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.
Drug Interactions Glipizide and Metformin Hydrochloride Tablets Certain drugs tend to produce hyperglycemia and may lead to loss of blood glucose control. These drugs include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving glipizide and metformin hydrochloride tablets, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving glipizide and metformin hydrochloride tablets, the patient should be observed closely for hypoglycemia. Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid as compared to sulfonylureas, which are extensively bound to serum proteins. Glipizide The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including non-steroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein-bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta-adrenergic blocking agents. When such drugs are administered to a patient receiving glipizide and metformin hydrochloride tablets, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving glipizide and metformin hydrochloride tablets, the patient should be observed closely for loss of blood glucose control. In vitro binding studies with human serum proteins indicate that glipizide binds differently than tolbutamide and does not interact with salicylate or dicumarol. However, caution must be exercised in extrapolating these findings to the clinical situation and in the use of glipizide and metformin hydrochloride tablets with these drugs. A…
WARNINGS WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL [see PRECAUTIONS]. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see PRECAUTIONS]. If metformin-associated lactic acidosis is suspected, immediately discontinue glipizide and metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see PRECAUTIONS]. SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to…