Metformin / Repaglinide Dosage

Usual Adult Dose for Diabetes Type 2

Individualize based on current therapy, effectiveness, and tolerability

Initial dose:
Patients inadequately controlled on metformin monotherapy: repaglinide 1 mg/metformin 500 mg orally twice a day with meals
Patients inadequately controlled on meglitinide monotherapy: current meglitinide dose with metformin 500 mg orally twice a day with meals
Patients receiving individual components concomitantly: current or similar dose of individual components without exceeding current dose

Titrate gradually based on glycemic control and tolerability
Maximum single dose: repaglinide 4 mg/metformin 1000 mg
Maximum daily dose: repaglinide 10 mg/metformin 2500 mg

Comments:

• To be given 2 to 3 times a day within 15 minutes prior to meal; if a meal is skipped, a dose should not be given for that meal.
• Patients who have not been previously treated with a meglitinide should be started on the lowest dose of repaglinide to reduce the risk of hypoglycemia.
• Blood glucose monitoring should be performed to assess therapeutic response.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already being treated with a meglitinide and metformin or who have inadequate glycemic control on a meglitinide alone or metformin alone.

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).

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

• 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.

IODINATED CONTRAST PROCEDURE:

• For patients with eGFR between 30 and 60 mL/min/1.73 m2: Stop this drug at the time of, or before imaging procedure; re-evaluate eGFR 48 hours after procedure; restart therapy only if renal function is stable.

• If renal dysfunction develops, this drug should be discontinued.

Liver Dose Adjustments

Hepatic impairment: Avoid use

Dose Adjustments

Debilitated or malnourished patients: Initial and maintenance doses should be conservative with careful dose titration.

Temporarily discontinue this drug in patients receiving iodinated contrast for radiological studies.

Dose adjustments may be necessary with concomitant use of CYP450 2C8 and CYP450 3A4 inhibitors and inducers.

Concomitant use with gemfibrozil is contraindicated.

This drug is not indicated for use in combination with NPH-insulin.

Precautions

US BOXED WARNING: Lactic Acidosis

• Lactic acidosis is a rare, but serious complication that may occur due to metformin accumulation.
• Increased risk is associated with renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure.
• Onset is often subtle, accompanied by nonspecific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence, and nonspecific gastrointestinal distress.
• Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate.
• If acidosis is suspected, immediately discontinue drug and hospitalize patient.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally before meals, usually within 15 minutes of a meal; however, may vary from immediately preceding meal to up to 30 minutes before a meal.
• Patients who skip a meal should be instructed to skip the dose for that meal; if an extra meal is taken, patients should be instructed to add a dose to cover the meal.

General:

• This drug is not indicated to treat patients with type 1 diabetes or diabetic ketoacidosis as these conditions should be treated with insulin.
• 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.

Monitoring:

• Periodic measures of fasting blood glucose and glycosylated hemoglobin should be performed to assess efficacy.
• Renal: Assess renal function baseline, repeat at least annually and more often as clinically indicated.
• Hematologic: Measure hematologic parameters annually

Patient advice:

• Advise patient 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.
• Patients should understand the importance of adhering to dietary instructions and regular physical activity; during periods of stress such as fever, trauma, infection, or surgery, management of diabetes may change and patients should be advised to seek medical advice.
• Patients should be aware of the symptoms of hypoglycemia and be careful about driving and the use of machinery, especially when optimum stabilization has not been achieved, e.g., during a transition from other medications or during irregular use.
• 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 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

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer