Pioglitazone

An FDA review concluded that although clinical trial data are inconsistent regarding the risk of bladder cancer in patients exposed to pioglitazone, there is still the potential for an increased risk and package labeling has been updated to reflect this. Avoid use of pioglitazone in patients with active bladder cancer and consider risks versus benefits prior to initiating therapy in patients with a history of bladder cancer.

Dose-related edema, including new-onset or exacerbation of existing edema, has been reported; use with caution in patients with edema. Monitor for signs/symptoms of heart failure.

An increased incidence of bone fractures in females treated with pioglitazone has been observed; majority of fractures occurred in the lower limb and distal upper limb. Consider risk of fracture prior to initiation and during use.

Thiazolidinediones, including pioglitazone, may cause or exacerbate heart failure; closely monitor for signs and symptoms of heart failure (eg, rapid weight gain, dyspnea, edema), particularly after initiation or dose increases; if heart failure develops, treat accordingly and consider dose reduction or discontinuation of pioglitazone. Not recommended for use in any patient with symptomatic heart failure. Initiation of therapy is contraindicated in patients with NYHA class III or IV heart failure; if used in patients with NYHA class I or II (systolic) heart failure, initiate at lowest dosage and monitor closely.

May decrease hemoglobin/hematocrit; effects may be related to increased plasma volume.

Hepatic failure, including fatalities, has been reported. Monitor for signs/symptoms of liver injury closely during therapy; discontinuation of therapy may be necessary.

The risk of hypoglycemia is increased when pioglitazone is combined with insulin or other diabetic medications; dosage adjustment of concomitant hypoglycemic agents may be necessary.

Has been reported with thiazolidinedione use, including pioglitazone; some patients with macular edema presented with blurred vision or decreased visual acuity, and most had peripheral edema at time of diagnosis. Patients should be seen by an ophthalmologist if any visual symptoms arise during therapy and all diabetic patients should have regular eye exams.

Dose-related weight gain observed with use; mechanism unknown but likely associated with fluid retention and fat accumulation. Disease-related concerns:

Mechanism requires the presence of insulin; therefore, use in type 1 diabetes (insulin dependent, IDDM) or diabetic ketoacidosis is not recommended.

Due to the possible risk of drug-induced liver injury, serum liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) should be obtained prior to initiation in all patients. In patients with abnormal hepatic tests, therapy should be initiated with caution. During therapy, if signs/symptoms of liver injury (eg, fatigue, anorexia, jaundice, dark urine, right upper abdominal discomfort) arise, interrupt pioglitazone therapy, obtain liver tests immediately and evaluate alternative etiologies. If an alternative etiology is not identified and serum ALT is >3 × ULN, do not resume therapy. Patients with serum ALT >3 × ULN and serum total bilirubin >2 × ULN are at risk for severe drug-induced liver injury. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.