Usual Adult Dose for Diabetes Type 2

Doses provided as glipizide-metformin

Patients with Inadequate Glycemic Control on Diet and Exercise Alone:

• Initial dose: 2.5 mg-250 mg orally once a day

Patients with Fasting Blood Glucose (FBG) between 280 and 320 mg/dL:

• Initial dose: 2.5 mg-500 mg orally twice a day

Maintenance Dose: Increase in increments of 2.5 mg-500 mg per day every 2 weeks to the minimum effective dose to achieve adequate blood glucose control
Maximum Initial Dose: 10 mg-1000 mg or 10 mg-2000 mg per day in divided doses

Patients with Inadequate Glycemic Control on Glipizide (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

Comments:

• Give with meals; initial doses should be conservative to avoid hypoglycemia largely due to glipizide 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 glipizide (or equivalent sulfonylurea) and metformin already being taken; the decision to switch to the nearest equivalent dose should be based on clinical judgement.
• 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

Severe renal impairment (eGFR less than 30 mL/min): Contraindicated
Moderate renal impairment (eGFR 30 to 45 mL/min/1.73 m2): Therapy initiation is not recommended
Moderate to mild renal impairment (eGFR greater than 45 mL/min/1.73 m2): No dose adjustments recommended

If during therapy, renal dysfunction develops, this drug should be discontinued:

• 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

• 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:

• See dosage adjustment section

Liver Dose Adjustments

Not recommended in patients with clinical or laboratory evidence of hepatic disease

IODINATED CONTRAST PROCEDURE:

• See dosage adjustment section

Dose Adjustments

Elderly, debilitated, and malnourished patients should generally not be titrated to the maximum dose to avoid the risk of hypoglycemia

IODINATED CONTRAST PROCEDURE: Discontinue at the time of, or prior to, an iodinated contrast imaging procedure in patients:

• Receiving intra-arterial iodinated contrast
• With eGFR 30 and 60 mL/min/1.73 m2
• With a history of liver disease, alcoholism or heart failure

Re-evaluate eGFR 48 hours after the imaging procedure; restart only if renal function is stable

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 glipizide

Precautions

US BOXED WARNING: LACTIC ACIDOSIS

• Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias; onset 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 (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally greater than 5 mcg/mL.
• Risk factors include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years 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 in the package labeling.
• If metformin-associated lactic acidosis is suspected, immediately discontinue therapy and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

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 with meals

Concomitant use with Colesevelam:

• Take at least 4 hours prior to colesevelam

General:

• Temporarily stop treatment prior to radiologic studies utilizing iodinated contrast materials (see dosage adjustment section) 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.

Monitoring:
Renal: Assess renal function baseline, repeat at least annually and more often as clinically indicated.
Hematologic: Measure hematologic parameters annually
Monitor glycemic control: Periodically measure fasting blood glucose and obtain HbA1C approximately every 3 months to assess efficacy

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information).
• 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 patient that this drug may need to be temporarily stopped when 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 patient to speak to healthcare provider if pregnant, intend to become pregnant, or are breastfeeding.