Glimepiride and Pioglitazone

Pioglitazone and glimepiride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a thiazolidinedione and sulfonylurea or who have inadequate glycemic control on a thiazolidinedione alone or a sulfonylurea alone. Pioglitazone and glimepiride tablets are a thiazolidinedione and a sulfonylurea 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 glimepiride is appropriate. Important Limitations of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis. Important Limitations of Use Pioglitazone exerts its antihyperglycemic effect only in the presence of endogenous insulin.

Pioglitazone and glimepiride tablets combine 2 antihyperglycemic agents with different mechanisms of action to improve glycemic control in patients with type 2 diabetes: pioglitazone, a member of the thiazolidinedione class, and glimepiride, a member of the sulfonylurea class. Thiazolidinediones are insulin-sensitizing agents that act primarily by enhancing peripheral glucose utilization, whereas sulfonylureas are insulin secretagogues that act primarily by stimulating release of insulin from functioning pancreatic beta cells. Pioglitazone Pioglitazone is a thiazolidinedione that depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is not an insulin secretagogue.

Individualize the starting dose of pioglitazone and glimepiride tablets based on the patient's current regimen. May adjust the dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of pioglitazone 45 mg and glimepiride 8 mg. Pioglitazone and glimepiride tablets should be given in a single dose once daily with meals. Obtain liver tests before starting pioglitazone and glimepiride tablets. If abnormal, use caution when treating with pioglitazone and glimepiride tablets, investigate the probable cause, treat (if possible) and follow appropriately. Monitoring liver tests while on pioglitazone and glimepiride tablets is not recommended in patients without liver disease.

Initiation in patients with established NYHA Class III or IV heart failure. Use in patients with known hypersensitivity to pioglitazone, glimepiride or any other component of pioglitazone and glimepiride tablets. Use in patients with known history of an allergic reaction to sulfonamide derivatives. Reported hypersensitivity reactions with glimepiride include cutaneous eruptions with or without pruritus as well as more serious reactions (e.g., anaphylaxis, angioedema, Stevens-Johnson Syndrome, dyspnea) Initiation in patients with established New York Heart Association (NYHA) Class III or IV heart failure. Hypersensitivity to sulfonamide derivatives.

Boxed warning (congestive heart failure): Thiazolidinediones, including pioglitazone, which is a component of pioglitazone and glimepiride tablets, cause or exacerbate congestive heart failure in some patients. After initiation of pioglitazone and glimepiride tablets and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). 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. Hypoglycemia: May be severe. When insulin or an insulin secretagogue is used with pioglitazone, a lower dose of the insulin or insulin secretagogue may be needed to reduce the risk of hypoglycemia.

The following serious adverse reactions are discussed elsewhere in the labeling: Congestive Heart Failure Hypoglycemia Edema Fractures Hemolytic Anemia Most common adverse reactions (≥5%) are upper respiratory tract infection, accidental injury, and combined edema/peripheral edema.

Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. Limit pioglitazone dose to 15 mg daily. CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone concentrations. Topiramate may decrease pioglitazone concentrations. Certain medications may affect glucose metabolism, requiring pioglitazone and glimepiride tablet dose adjustment and close monitoring of blood glucose. Miconazole: Severe hypoglycemia can occur when pioglitazone and glimepiride tablets and oral miconazole are used concomitantly. CYP2C9 interactions: Inhibitors and inducers may affect glycemic control by altering glimepiride plasma concentrations. Colesevelam: Coadministration may reduce glimepiride absorption. Pioglitazone and glimepiride tablets should be administered at least 4 hours prior to colesevelam.

Store at 25°C (77°F), excursions permitted to 15° to 30°C (59° to 86°F). Keep container tightly closed and protect from moisture and humidity.