Glipizide/Metformin HCl

A to Z Drug Facts

 Action Glipizide: Decreases blood glucose by stimulating insulin release from pancreas and by increasing tissue sensitivity to insulin.

Metformin: decreases blood glucose by reducing hepatic glucose production and may decrease intestinal absorption of glucose and increase response to insulin.

 Indications Initial treatment 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; 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 Patients with renal disease or renal dysfunction, which also may result from conditions such as cardiovascular collapse, acute MI, and septicemia; CHF requiring pharmacologic treatment; acute or chronic metabolic acidosis, with or without coma; known hypersensitivity to any component of the product.

 Route/Dosage

Dosage must be individualized on the basis of both effectiveness and tolerance, while not exceeding the max recommended daily dose of 20 mg glipizide or 2000 mg metformin.

Initial Therapy

Adults PO Recommended starting dose is 2.5 mg/250 mg once daily with a meal. For patients whose fasting plasma glucose (FPG) is 280 to 320 mg/dL a starting dose of 2.5 mg/500 mg bid should be considered. Dosage increases, to achieve adequate glycemic control, should be made in increments of 1 tablet/day q 2 wk to a max of 10 mg/1000 mg or 10 mg/2000 mg/day in divided doses. Efficacy in patients whose FPG is greater than 320 mg/dL has not been established.

Second-Line Therapy

Adults PO Recommended starting dose is 2.5 mg/500 mg or 5 mg/500 mg bid with morning and evening meals. To avoid hypoglycemia, the starting dose should not exceed the daily doses of glipizide or metformin already being taken. Titrate the daily dose in increments of no more than 5 mg/500 mg up to the maximum effective dose that adequately controls blood glucose but not exceeding 20 mg/2000 mg/day. Patients previously treated with combination therapy of glipizide plus metformin may be switched to 2.5 mg/500 mg or 5 mg/500 mg; however, the starting dose should not exceed the daily dose of glipizide or equivalent dose of another sulfonylurea and metformin already being taken.

 Interactions

Alcohol The effects of metformin on lactate metabolism may be potentiated. Beta adrenergic blocking agents, chloramphenicol, ciprofloxacin, coumarin anticoagulants, MAO inhibitors, miconazole, NSAIDs, probenecid, salicylates, sulfonamides May potentiate the hypoglycemic action of glipizide. Calcium channel blocking agents, corticosteroids, estrogens, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, phenytoin, sympathomimetics, thiazides and other diuretics, thyroid products These agents tend to produce hyperglycemia and may lead to loss of blood glucose control. Furosemide Metformin plasma levels may be elevated while furosemide levels may be decreased. Nifedipine Metformin plasma levels may be increased.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypertension. CNS: Dizziness. GI: Diarrhea; nausea; vomiting; abdominal pain. GU: Urinary tract infection. METABOLIC: Hypoglycemia. RESPIRATORY: Upper respiratory tract infections. OTHER: Musculoskeletal pain.

 Precautions

Pregnancy: Category C. Lactation: Undetermined; however, some sulfonylurea drugs are known to be excreted in breast milk. Children: Safety and efficacy not established. Elderly: In general, elderly patients are not titrated to the maximum dose because of age-related decreases in renal function. CV mortality: Oral hypoglycemic agents have been associated with increased cardiovascular mortality compared with treatment with diet alone or diet plus insulin. Iodinated contrast materials: Metformin therapy should be withheld at the time of or prior to parenteral contrast studies with iodinate materials. Reinstitute therapy 48 hr after the study and after renal function has been determined to be normal. Lactic acidosis: Lactic acidosis can occur as a result of metformin accumulation (eg, renal impairment) or in pathophysiologic conditions associated with tissue hypoperfusion and hypoxia. The risk of lactic acidosis increases with the degree of renal dysfunction and the age of the patient. Renal/Hepatic disease: Metabolism and excretion of glipizide may be slowed in patients with impaired renal or hepatic function. Decreased renal function results in decreased renal clearance and prolongation of the metformin t_1/2. Concomitant medications that affect renal function may result in hemodynamic changes or interfere with disposition of metformin (eg, cationic drugs) and should be used with caution. Avoid metformin in patients whose serum creatinine levels exceed the upper limit of normal for their age or with clinical or laboratory evidence of hepatic disease.

 Administration/Storage

• Do not administer to patients with renal impairment or to patients with type 1 diabetes mellitus.
• Refer to manufacturer's dosing chart when converting patients from glipizide or metformin monotherapy to combination therapy.
• Administer dose bid as prescribed.
• Administer each dose with food to prevent GI distress.
• Store at controlled room temperature (68° to 77°F).

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note history of renal disease, liver disease, CHF or edema, chronic metabolic acidosis, or acute metabolic acidosis (eg, diabetic ketoacidosis).
• Ensure that renal function, hemoglobin, and hematocrit, and RBC indices have been assessed prior to starting therapy and at least annually during therapy.
• Ensure that creatinine clearance has been determined in patients greater than 80 yr before initiating therapy.
• Check blood sugars frequently and observe for signs of hypoglycemia. Inform health care provider if blood sugar readings are outside target range or if hypoglycemic events are noted.
• Ensure that medication is withheld before, and for 48 hr after, undergoing a radiologic study with intravascular administration of iodinated contrast material and is not restarted until renal function has been documented to be normal.
• Hold therapy in patient undergoing surgical procedure until oral intake has resumed and renal function has been documented to be normal.

 Patient/Family Education

• Explain name, dose, action, and potential side effects of drug.
• Advise patient to take prescribed dose bid and to take with food to decrease GI distress.
• Advise patient that dose may be gradually increased q 2 wk until maximum benefit is obtained.
• Educate patient, family or caregiver regarding type 2 diabetes and its management, including target ranges for blood sugar control.
• Instruct patient that this drug is not a substitute for diet and exercise and that patient should continue to follow prescribed regimens.
• Emphasize the importance of regular daily blood glucose monitoring and periodic hemoglobin A_1c (HbA_1c) tests.
• Advise patient to keep a log of measured blood sugars and to take to each visit with the health care provider.
• Advise patient to carry medical identification indicating diabetes (eg, Medi-Alert).
• Caution patient to avoid excessive alcohol intake to reduce risk of metabolic acidosis.
• Instruct patient to report any of the following to health care provider immediately: general body discomfort, muscle aches, unexplained rapid breathing or shortness of breath, unexplained drowsiness, nausea, vomiting, abdominal pain.
• Review symptoms of hypoglycemia and hyperglycemia and action plans to undertake in the event either occur.
• Instruct patient to notify health care provider if experiencing hypoglycemic episodes or if measured blood sugars are outside target range.
• Advise women to inform health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Instruct patient not to take prescription or OTC drugs or dietary supplements without consulting health care provider.
• Advise patient that follow-up visits and lab tests will be necessary to monitor therapy and to and keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts