Pioglitazone Hydrochloride And Metformin Hydrochloride

1 INDICATIONS AND USAGE Pioglitazone and metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both pioglitazone and metformin is appropriate [see Clinical Studies (14) ] . Pioglitazone and metformin hydrochloride tablets are a thiazolidinedione and biguanide combination product indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both pioglitazone and metformin is appropriate. (1 , 14) Important Limitations of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis.

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) ] Lactic acidosis [see Boxed Warning and Warnings and Precautions (5.2) ] Edema [see Warnings and Precautions (5.3) ] Fractures [see Warnings and Precautions (5.7) ] Most common adverse reactions (>5%) are upper respiratory tract infection, edema, diarrhea, headache and weight gain. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary Limited data with pioglitazone and metformin hydrochloride or pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations].

WARNING: CONGESTIVE HEART FAILURE AND LACTIC ACIDOSIS Congestive Heart Failure Thiazolidinediones, including pioglitazone, which is a component of pioglitazone and metformin hydrochloride, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions (5.1) ] . 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) Lactic acidosis: See boxed warning. (5.2 ) Edema: Dose-related edema may occur. (5.3) 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. (5.4) Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. 4 CONTRAINDICATIONS Initiation in patients with established NYHA Class III or IV heart failure [see Boxed Warning ] . Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.2) ] . Use in patients with known hypersensitivity to pioglitazone, metformin, or any other component of pioglitazone and metformin hydrochloride tablets.