Glyburide / Metformin Dosage
Medically reviewed by Drugs.com. Last updated on March 31, 2020.
Applies to the following strengths: 1.25 mg-250 mg; 2.5 mg-500 mg; 5 mg-500 mg
Usual Adult Dose for:
Additional dosage information:
Usual Adult Dose for Diabetes Type 2
Doses provided as glyburide-metformin
-As Initial Therapy in Patients with Inadequate Glycemic Control on Diet and Exercise Alone:
Starting dose: 1.25 mg-250 mg orally once a day
-Consider a starting dose of 1.25 mg-250 mg orally twice a day for patients with fasting blood glucose (FBG) greater than 200 mg/dL or HbA1c greater than 9%
Maintenance Dose: Increase in increments of 1.25 mg-250 mg per day every 2 weeks up to the minimum effective dose to achieve glycemic control
Maximum Initial Dose: 10 mg-2000 mg per day
-Patients with Inadequate Glycemic Control on a Glyburide (or another Sulfonylurea) and/or Metformin:
Initial dose: 2.5 mg-500 mg or 5 mg-500 mg orally twice a day
Maintenance Dose: Increase in increments of no more than 5 mg-500 mg to the minimum effective dose to achieve adequate blood glucose control
Maximum Dose: 20 mg-2000 mg per day
-Give with meals; 5 mg-500 mg dose should not be used as initial therapy due to an increased risk of hypoglycemia; initial doses should be conservative to avoid hypoglycemia largely due to glyburide and gastrointestinal side effects largely due to metformin.
-For patients who are switching to combination therapy, initial doses should not exceed the daily dose of glyburide (or equivalent sulfonylurea) and metformin already being taken; the decision to switch to the nearest equivalent dose should be based on clinical judgement.
-Addition of thiazolidinedione may be appropriate for patients not adequately controlled on glyburide-metformin; in patients experiencing hypoglycemia, consider reducing the dose of the glyburide component.
-Monitor patients closely for signs and symptoms of hypoglycemia.
Use: As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
Renal Dose Adjustments
-Contraindicated in patients with renal disease (e.g. males with serum creatinine levels of 1.5 mg/dL or greater, females with serum creatinine of 1.4 or greater, or abnormal creatinine clearance).
-Contraindicated in patients with conditions that may cause renal disease or renal dysfunction such as cardiovascular collapse (shock), acute myocardial infarction and septicemia.
-Not recommended in patients with serum creatinine levels above the upper limit of normal for their age.
-Do not initiate in patients 80 years or older unless measurement of CrCl demonstrates renal function is not reduced.
-If renal dysfunction develops, this drug should be discontinued.
New Metformin Renal Dosing: Obtain eGFR prior to initiating therapy:
-eGFR less than 30 mL/min/1.73 m2: Use is contraindicated
-eGFR 30 to 45 mL/min/1.73 m2: Initiating therapy is not recommended
-eGFR that falls below 30 mL/min/1.73 m2 during therapy: Discontinue therapy
-eGFR that falls below 45 mL/min/1.73 m2 during therapy: Assess risks versus benefit of continued therapy
-eGFR greater than 45 mL/min/1.73 m2: No dose adjustments recommended
-Use with caution; initial and maintenance doses should be conservative to avoid hypoglycemic reactions
-Initial dose: 1.25 mg (standard) or 0.75 mg (micronized) orally once a day.
Liver Dose Adjustments
Not recommended in patients with clinical or laboratory evidence of hepatic disease.
Elderly, debilitated, and malnourished patients should generally not be titrated to the maximum dose to avoid the risk of hypoglycemia
Temporarily stop treatment prior to radiologic studies utilizing iodinated contrast materials and for surgical procedures when restricted food or fluid intake is expected; may resume once adequate renal function is confirmed
Concomitant Thiazolidinedione Use:
-Addition of thiazolidinedione may be appropriate for patients not adequately controlled on glyburide-metformin
-Thiazolidinedione should be initiated and titrated at its recommended doses; however, with the addition of a thiazolidinedione, there is an increased risk of hypoglycemia
-For patients who experience hypoglycemia, consider reducing the glyburide component; as clinically warranted, additional adjustment of the antidiabetic regimen should also be considered.
Concomitant Use with Colesevelam:
-This drug should be administered at least 4 hours prior to colesevelam to ensure that colesevelam does not reduce the absorption of glyburide.
US BOXED WARNING: LACTIC ACIDOSIS
-Lactic acidosis is a rare, but serious metabolic complication that may occur due to metformin accumulation; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may occur in association with a number of pathophysiologic conditions, including diabetes, and/or whenever there is significant tissue hypoperfusion and hypoxemia; it is characterized by elevated blood lactate levels (greater than 5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and increased lactate/pyruvate ratio; when metformin is implicated as the cause of lactic acidosis, metformin plasma levels are generally greater than 5 mcg/mL.
-The reported incidence of lactic acidosis in patients receiving metformin is approximately 0.03 cases per 1000 patient-years, with approximately 0.015 fatal cases per 1000 patient-years. In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have primarily occurred in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications.
-Patients with congestive heart failure requiring pharmacologic management, especially those who are at risk of hypoperfusion and hypoxemia are at increased risk.
-Increased risk is associated with advancing age and degree of renal impairment, therefore, regular monitoring of renal function and use of the minimum effective dose is recommended; metformin should not be initiated in patients 80 years or older without demonstration of adequate renal function.
-Metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis.
-This drug should be generally avoided in patients with clinical or laboratory evidence of hepatic disease as impaired hepatic function may significantly limit the ability to clear lactate; patients should be cautioned against excessive alcohol intake, either acute or chronic since alcohol potentiates the effects of metformin on lactate metabolism.
-Additionally this drug should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure.
-Onset of lactic acidosis is often subtle, accompanied by nonspecific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence, and nonspecific gastrointestinal (GI) distress; there may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. GI symptoms, while common on therapy initiation, generally abate with continued use; later occurrence of GI symptoms could be due to lactic acidosis or other serious disease.
-Laboratory abnormalities include low pH, increased anion gap, elevated blood lactate and increased blood metformin levels.
-If acidosis is suspected, immediately discontinue drug and hospitalize patient.
-Because metformin is dialyzable (with a clearance up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
No data available.
-Take orally with meals
-Take at least 4 hours prior to colesevelam to ensure that colesevelam does not reduce the absorption of glyburide
-Temporarily stop treatment prior to radiologic studies utilizing iodinated contrast materials and for surgical procedures when restricted food or fluid intake is expected; may resume once adequate renal function is confirmed.
-When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma infection, or surgery, it may be necessary to stop this drug and administer insulin.
-Consider use of a non-sulfonylurea agent in patients with G6PD deficiency.
Renal: Assess renal function baseline, repeat at least annually and more often as clinically indicated.
Hematologic: Measure hematologic parameters annually
Monitor glycemic control: Periodic fasting blood glucose and HbA1c
-Patients should be informed of the importance of adhering to a diet with a regular distribution of carbohydrates throughout the day, regular physical exercises, and regular checks on glycemic control.
-Patients should understand the risks of hypoglycemia, know how to recognize the symptoms, and be prepared to treat.
-Inform patients about the risk of lactic acidosis, conditions that might predispose them to its occurrence, and symptoms to watch for and report.
-Advise patients that this drug will need to be temporarily stopped if undergoing radiologic studies with intravascular iodinated contrast materials or surgical procedures that will limit food or fluid intake.
-Advise patients on the risks of excessive alcohol intake.
-Tell patients that while gastrointestinal symptoms might be common when initiating treatment, gastrointestinal problems after initiation should be reported.
-Advise patients to speak to healthcare provider if pregnant, intend to become pregnant, or are breastfeeding.
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