Usual Adult Dose for Diabetes Type 2

Individualize dose based on safety, efficacy, and prior therapy

Initial dose: pioglitazone 30 mg-glimepiride 2 mg or pioglitazone 30 mg-glimepiride 4 mg orally once a day

• For patients inadequately controlled on glimepiride monotherapy: pioglitazone 30 mg-glimepiride 2 mg or pioglitazone 30 mg-glimepiride 4 mg orally once a day
• For patients inadequately controlled on pioglitazone monotherapy: pioglitazone 30 mg-glimepiride 2 mg orally once a day
• For patients receiving pioglitazone and glimepiride as individual components: Initiate with the combination product containing doses that are as close as possible to the dose of each component
• For patients currently on a different sulfonylurea monotherapy or switching from combination therapy of pioglitazone plus a different sulfonylurea: pioglitazone 30 mg-glimepiride 2 mg orally once a day
• For patients with systolic dysfunction, initiate with pioglitazone monotherapy and only initiate combination therapy after titration from pioglitazone 15 mg to 30 mg has been safely tolerated.

Maintenance Dose: Gradually titrate dose based on adequacy of therapeutic response and tolerability for each component

Comments:

• Take with first meal of the day.
• For patients switching from a different sulfonylurea, carefully monitor for hypoglycemia for 1 to 2 weeks due to a potential overlapping drug effect.
• If hypoglycemia occurs in a patient coadministered an insulin secretagogue, the dose of the insulin secretagogue should be reduced.
• If hypoglycemia occurs in a patient's coadministered insulin, the insulin dose should be decreased by 10% to 25% with further adjustments based on glycemic response.

Use: As an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes mellitus who are already treated with a thiazolidinedione and sulfonylurea or who have inadequate glycemic control in a thiazolidinedione alone or a sulfonylurea alone.

Renal Dose Adjustments

Use with caution: Initial dosing, dose increments, and maintenance dosage should be conservative to minimize the risk of hypoglycemia.

Liver Dose Adjustments

Use with caution; Liver tests (ALT, AST, alkaline phosphatase, total bilirubin) should be obtained prior to initiating therapy.

• Routine monitoring of liver tests is not recommended in patients without liver disease.
• For patients who experience signs or symptoms indicative of liver injury, liver tests should be performed promptly.
• For ALT elevations greater than 3 times the upper limit of normal (3 x ULN), treatment should be interrupted and an investigation done for probable cause; this drug should not be started without another explanation for the liver test abnormality.
• For ALT elevations greater than 3 x ULN with total bilirubin of greater than 2 x ULN without alternative etiologies, this drug should not be restarted.
• For lesser elevations of ALT or bilirubin and with an alternate probable cause, treatment may proceed with caution.

Dose Adjustments

• If signs or symptoms of heart failure develop, dose reduction or drug discontinuation of pioglitazone should be considered.

• Elderly, debilitated, or malnourished patients: Dose conservatively to avoid hypoglycemia

Concomitant Use with Insulin or Insulin Secretagogue

• If hypoglycemia occurs in a patient coadministered an insulin secretagogue, the dose of the insulin secretagogue should be reduced.
• If hypoglycemia occurs in a patient's coadministered insulin, the insulin dose should be decreased by 10% to 25% with further adjustments based on glycemic response.

Concomitant Use with Strong CYP450 2C8 Inhibitors:

• If concomitantly administered with a strong CYP450 2C8 inhibitor, the maximum dose of pioglitazone should be 15 mg once a day; therefore, patients should be switched to individual components

Precautions

US BOXED WARNING: Congestive Heart Failure

• Thiazolidinediones, including pioglitazone, may cause or exacerbate congestive heart failure in some patients.
• After initiation of therapy and with any dosage increases, observe patients carefully for signs and symptoms of heart failure including excessive, rapid weight gain, dyspnea, and/or edema; if signs and symptoms of heart failure develop, manage in accordance to current standards of care.
• Drug discontinuation or dosage reduction should be considered in patients showing signs and symptoms of heart failure; this drug is not recommended in patients with symptomatic heart failure.
• Initiation in patients with established NYHA Class III or IV heart failure is contraindicated.

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 once a day with first main meal of the day
• When coadministered with colesevelam, this drug should be taken at least 4 hours prior

General:

• This drug should be used with caution in patients with liver disease.
• This drug should not be used in patients with symptomatic heart failure.
• Hypoglycemia may occur, especially in the elderly, debilitated, or malnourished patient, and/or those with renal, hepatic or adrenal insufficiency; dose reduction of glimepiride may be necessary.
• This drug should not be used in patients with type 1 diabetes or diabetic ketoacidosis.
• Hemolytic anemia may occur in glucose 6-phosphate dehydrogenase (G6PD) deficient patients; consider a non-sulfonylurea alternative.

Monitoring:

• Hepatic: ALT, AST, alkaline phosphatase, and total bilirubin should be obtained prior to starting therapy; routine monitoring in patients without liver disease is not recommended; however, repeat tests should be ordered promptly in patients showing signs or symptoms of liver injury.
• Observe closely for signs and symptoms of heart failure with initiation and with each dose increase.
• Monitor glycemic control.

Patient advice:

• This drug may cause edema; patients experiencing rapid weight gain, shortness of breath or other symptoms of heart failure should notify their health care professional promptly.
• Premenopausal anovulatory women may be at risk for pregnancy while on this drug; pregnancy risk should be discussed with patient and adequate contraception recommended if necessary.
• Patients should be told to stop taking this medication and seek medical attention for unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine as they may be a signs of hepatotoxicity.
• Patients should be instructed to report development or worsening of dysuria, urinary urgency, or any blood in the urine
• Patients should be informed about the risks of hypoglycemia, its symptoms, the conditions that might predispose them to develop it, and treatment.
• Patients should speak with their health care provider during periods of stress such as fever, trauma, infection, or surgery, as their diabetes management may need to be changed.