Pioglitazone

1 INDICATIONS AND USAGE Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [ see Clinical Studies ( 14 ) ]. Important Limitations of Use Pioglitazone tablets exert their antihyperglycemic effect only in the presence of endogenous insulin. Pioglitazone tablets should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings. Use caution in patients with liver disease [ see Warnings and Precautions ( 5.3 ) ].

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Congestive heart failure [ see Boxed Warning and Warnings and Precautions ( 5.1 ) ] Edema [ see Warnings and Precautions ( 5.5 ) ] Fractures [ see Warnings and Precautions ( 5.6 ) ] Most common adverse reactions (≥ 5%) are upper respiratory tract infection, headache, sinusitis, myalgia, and pharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary Limited data with pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [ see Clinical Considerations ]. In animal reproduction studies, no adverse developmental effects were observed when pioglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 5- and 35-times the 45 mg clinical dose, respectively, based on body surface area [ see Data ].

WARNING: CONGESTIVE HEART FAILURE Thiazolidinediones, including pioglitazone hydrochloride, cause or exacerbate congestive heart failure in some patients [ see Warnings and Precautions ( 5.1 ) ]. After initiation of pioglitazone hydrochloride, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). 5 WARNINGS AND PRECAUTIONS Congestive heart failure: Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Monitor patients for signs and symptoms. ( 5.1 ) Hypoglycemia: When used with insulin or an insulin secretagogue, a lower dose of the insulin or insulin secretagogue may be needed to reduce the risk of hypoglycemia. ( 5.2 ) Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. If liver injury is detected, promptly interrupt pioglitazone hydrochloride and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. 4 CONTRAINDICATIONS Initiation in patients with established NYHA Class III or IV heart failure [ see Boxed Warning ]. Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets. Initiation in patients with established New York Heart Association (NYHA) Class III or IV heart failure [ see Boxed Warning ].