Usual Adult Dose for Diabetes Type 2

• Patients without congestive heart failure:

Initial dose: 15 mg or 30 mg orally once a day

• Patients with congestive heart failure (New York Heart Association [NYHA] Class I or II):

Initial dose: 15 mg orally once a day

Maintenance dose: 15 mg to 45 mg orally once a day based on glycemic response as determined by HbA1c
Maximum dose: 45 mg orally once a day

Comments:

• This drug exerts its antihyperglycemic effect only in the presence of endogenous insulin and therefore is not expected to be effective in patients with type 1 diabetes mellitus or diabetic ketoacidosis.
• Patients concomitantly receiving an insulin secretagogue or insulin may need to reduce the dose of the insulin secretagogue or insulin if hypoglycemia occurs.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

Use with caution in patients with liver disease.

• Obtain liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to initiating therapy.
• Promptly perform liver function tests if symptoms suggestive of liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice develop.
• If ALT is greater than 3 times the upper limit of normal (ULN), interrupt therapy and investigate cause.
• Do not restart therapy if ALT is greater than 3 x ULN and total bilirubin greater than 2 x ULN without alternative etiologies as there is a risk for severe drug-induced liver injury.
• Treatment may be restarted with caution for patients with lesser elevations of ALT or bilirubin and an alternative probable cause.

Dose Adjustments

Concomitant use with an insulin secretagogue (e.g., sulfonylurea): If hypoglycemia occurs, the dose of the insulin secretagogue should be reduced.

Concomitant use with insulin: If hypoglycemia occurs, the dose of insulin should be reduced by 10% to 25%. Additional adjustments to the insulin dose should be individualized based on glycemic response.

Concomitant use with Gemfibrozil or Other Strong CYP450 2C8 Inhibitors:
Maximum recommended daily dose: 15 mg

For Patients with Congestive Heart Failure (NYHA Class I or II)
Initial dose: 15 mg orally once a day

Precautions

US BOXED WARNINGS:

• Thiazolidinediones cause or exacerbate congestive heart failure in some patients.
• After initiation of therapy, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone must be considered.
• Pioglitazone is not recommended in patients with symptomatic heart failure.
• Initiation of therapy in patients with established New York Heart Association (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 or without meals

Storage requirements:

• Protect from light, moisture and humidity

General:

• This drug is contraindicated for use in patients with NYHA Class III or IV Heart Failure (HF), not recommended in patients with symptomatic HF, and should be initiated at reduced doses in patients with NYHA Class I or II HF.
• This drug should be used cautiously in patients with liver disease.
• This drug should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
• The US FDA has released an updated review evaluating the risk of bladder cancer and it concludes that use of this drug may be linked to an increased risk of bladder cancer; while a 10-year epidemiologic study did not find an increased risk, other studies have shown risk. This drug should not be used in patients with active bladder cancer and should be used very carefully in patients with a history of bladder cancer.

Monitoring:

• Monitor closely for signs and symptoms of heart failure (e.g., weight gain, edema), especially with concomitant insulin use.
• Perform liver function tests (LFTs) prior to initiation; if symptoms suggestive of liver injury develop, LFTs should be performed promptly; routine monitoring of LFTs in patients without liver disease is not recommended
• Monitor glycemic control
• Assess and maintain bone health according to current standards, especially in female patients
• Patients with diabetes should have regular eye exams by an ophthalmologist

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 with use of this drug; pregnancy risk should be discussed 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 signs of hepatotoxicity.
• Patients should be instructed to report blood or red color in the urine, new or worsening urge to urinate, or pain when urinating as they may be signs of bladder cancer.
• 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.