Glipizide / Metformin Hydrochloride

Pronunciation: GLIP-i-zide/met-FOR-min HYE-droe-KLOR-ide
Class: Antidiabetic combination

Trade Names

Glipizide/Metformin Hydrochloride
- Tablets 2.5 mg/500 mg
- Tablets 5 mg/500 mg

Metaglip
- Tablets 2.5 mg/250 mg

Pharmacology

Glipizide

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

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Metformin

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

Indications and Usage

As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes.

Contraindications

Patients with renal disease or renal function impairment, which also may result from conditions such as CV collapse, acute MI, and septicemia; acute or chronic metabolic acidosis, with or without coma; known hypersensitivity to any component of the product. Temporarily discontinue therapy in patients undergoing radiologic studies involving intravascular administration of iodinated contrast media.

Dosage and Administration

Dosage must be individualized on the basis of both efficacy and tolerance, while not exceeding the max recommended daily dose of glipizide 20 mg or metformin 2,000 mg.

Inadequate Glycemic Control on a Sulfonylurea and/or Metformin
Adults

PO Recommended starting dosage is 2.5 mg/250 mg every day with a meal. For patients whose fasting plasma glucose (FPG) is 280 to 320 mg/dL, consider a starting dosage of 2.5 mg/500 mg twice daily. Make dosage increases, to achieve adequate glycemic control, in increments of 1 tablet/day every 2 wk to a max of 10 mg/1,000 mg or 10 mg/2,000 mg/day in divided doses. Efficacy in patients whose FPG is more than 320 mg/dL has not been established.

Inadequate Glycemic Control on Diet and Exercise Alone
Adults

PO Recommended starting dosage is 2.5 mg/500 mg or 5 mg/500 mg twice daily with morning and evening meals. To avoid hypoglycemia, starting dose should not exceed daily doses of glipizide or metformin already being taken. Titrate daily dose in increments of no more than 5 mg/500 mg up to minimum effective dose that adequately controls blood glucose but not exceeding 20 mg/2,000 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.

Storage/Stability

Store at controlled room temperature (59° to 86°F).

Drug Interactions

Alcohol

The effects of metformin on lactate metabolism may be potentiated.

Beta-adrenergic blocking agents, chloramphenicol, ciprofloxacin, coumarin anticoagulants, MAOIs, 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.

Cationic drugs (eg, amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin)

May compete with metformin for renal tubular secretion, elevating metformin concentrations and increasing the pharmacologic effects.

Cyclosporine

Cyclosporine and glipizide concentrations may be elevated, increasing the pharmacologic effects and adverse reactions.

Fluconazole

Glipizide concentrations may be elevated, increasing the pharmacologic effect.

Furosemide

Metformin plasma levels may be elevated, while furosemide levels may be decreased.

Nifedipine

Metformin plasma levels may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (4%).

CNS

Headache (13%); dizziness (5%).

GI

Diarrhea (18%); nausea/vomiting (8%); abdominal pain (6%).

Genitourinary

UTI (1%).

Metabolic-Nutritional

Hypoglycemia (13%).

Musculoskeletal

Musculoskeletal pain (8%).

Respiratory

Upper respiratory tract infection (10%).

Precautions

Warnings

Lactic acidosis is a rare but serious metabolic complication that can occur because of metformin accumulation during treatment with glipizide/metformin. When it occurs, it is fatal in approximately 50% of cases.


Monitor

Check blood sugar frequently and observe for signs of hypoglycemia. Monitor glycosylated hemoglobin (HbA 1c ) every 3 mo. Assess renal function and verify as healthy before starting therapy and at least annually thereafter. Monitor Hct, Hgb, and RBCs before starting therapy and periodically thereafter. Monitor patient for signs or symptoms of metabolic acidosis (eg, abdominal pain, malaise, myalgia, nausea, respiratory distress, unexplained drowsiness, vomiting).


Pregnancy

Category C . However, not recommended for use during pregnancy.

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 max dose because of age-related decreases in renal function. Determine CrCl in patients older than 80 y of age before initiating therapy.

Renal Function

Metabolism and excretion of glipizide may be slowed in patients with renal function impairment. Decreased renal function results in decreased renal Cl and prolongation of the metformin half-life. 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 ULN for their age or with clinical or laboratory evidence of hepatic disease. Determine CrCl in patients older than 80 y of age before initiating therapy.

Hepatic Function

Metabolism and excretion of glipizide may be slowed in patients with hepatic function impairment. Avoid metformin in patients with clinical or laboratory evidence of hepatic disease because of increased risk of lactic acidosis.

CV mortality

Oral hypoglycemic agents have been associated with increased CV mortality compared with treatment with diet alone or diet plus insulin.

Hypoglycemia

May occur. The risk is increased when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use of other glucose-lowering agents or alcohol.

Hypoxic states

Hypoxemic conditions have been associated with lactic acidosis and may also cause prerenal azotemia. Promptly discontinue therapy if these events occur.

Iodinated contrast materials

Withhold metformin therapy at the time of or prior to parenteral contrast studies with iodinated materials. Reinstitute therapy 48 h after the study and after renal function has been determined to be healthy.

Lactic acidosis

Lactic acidosis can occur as a result of metformin accumulation (eg, renal function impairment) or in pathophysiologic conditions associated with tissue hypoperfusion and hypoxia. The risk of lactic acidosis increases with the degree of renal function impairment and the age of patient.

Surgery

Hold therapy in patient undergoing surgical procedure until oral intake has resumed and renal function has been documented to be normal.

Vitamin B 12

A decrease in vitamin B 12 levels to subnormal may occur. Supplementation may be necessary.

Overdosage

Symptoms

Glipizide

Coma, hypoglycemia, neurological impairment, seizures.

Metformin

Lactic acidosis.

Patient Information

  • Educate patient regarding diabetes and its management, including target ranges for blood sugar control. Advise patient that medication is not a substitute for diet and exercise and to continue to follow prescribed regimens.
  • Educate patient or caregiver regarding potential long-term complications of diabetes and the need for regular physical and eye examinations.
  • Advise patient to read patient information leaflet before starting therapy and with each refill.
  • Advise patient to take prescribed dose once or twice daily and to take with food to decrease GI distress.
  • Advise patient that dose may be gradually increased every 2 wk until max benefit is obtained.
  • Ensure that patient understands how to use home glucose monitor and has a plan for monitoring and recording blood sugar measurements (eg, log). Advise patient to take log to each visit with health care provider.
  • Educate patient regarding value of periodic HbA 1c testing to confirm level of glucose control.
  • Advise patient to discuss with health care provider a plan for managing each of the following situations: medication dosing during intercurrent conditions (eg, infection, sick days, stress, trauma, vomiting); accidental administration of too little or too much medication; missed dose; inadequate food intake or a skipped meal; travel across time zones; change in physical activity.
  • Advise patient to carry medical identification (eg, card, bracelet) of diabetes.
  • Caution patient to avoid excessive alcohol intake to reduce risk of lactic acidosis.
  • Instruct patient to report any of the following to health care provider immediately: abdominal pain, general body discomfort, muscle aches, nausea, unexplained drowsiness, unexplained rapid breathing or shortness of breath, or vomiting.
  • 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.

Copyright © 2009 Wolters Kluwer Health.

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