Actoplus Met

Actoplus Met

Pioglitazone and metformin tablets
TAKEDACombination therapy approved for type 2 diabetes

Pioglitazone acts primarily by decreasing insulin resistance, while metformin improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. The combination of pioglitazone and metformin was approved on August 29, 2005, as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of pioglitazone and metformin or whose diabetes is not adequately controlled with metformin alone, or for those patients who have initially responded to pioglitazone alone and require additional glycemic control.

Safety. The combination of pioglitazone and metformin is contraindicated in patients with renal disease or dysfunction and/or acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. The combination of pioglitazone and metformin should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials. Use of such products may result in acute alteration of renal function. Lactic acidosis can occur due to metformin accumulation during treatment with combination pioglitazone and metformin. The onset of lactic acidosis is often subtle and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Patients should be made aware of these symptoms and instructed to notify their physician immediately if they occur. Like other thiazolidinediones, pioglitazone can cause fluid retention when used alone or in combination with other antihyperglycemic agents, including insulin. This fluid retention may lead to or exacerbate heart failure. Combination pioglitazone and metformin is not recommended in patients with New York Heart Association (NYHA) Class III or IV cardiac status. Patients receiving pioglitazone in combination with insulin or oral hypoglycemic agents may be at risk for hypoglycemia, and a reduction in the dose of the concomitant agent may be necessary. In all patients, serum alanine aminotransferase (ALT) levels should be evaluated prior to the initiation of therapy with combination pioglitazone and metformin and periodically thereafter based on the clinical judgment of the healthcare professional. Therapy with combination pioglitazone and metformin should not be initiated if the patient exhibits clinical evidence of active liver disease or the ALT levels exceed 2.5 times the upper limit of normal (ULN). Therapy with combination pioglitazone and metformin should be temporarily discontinued for any major surgical procedure and should not be resumed until the patient's oral intake has resumed and renal function has been evaluated as normal. Combination pioglitazone and metformin therapy should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. The most common adverse events associated with the use of pioglitazone and metformin include upper respiratory tract infection, diarrhea, combined and peripheral edema, and headache.

Dosing. For patients inadequately controlled on metformin monotherapy, pioglitazone/metformin may be initiated at either the 15/500-mg or 15/850-mg dose once or twice daily, and gradually titrated after assessing adequacy of response. Patients who initially respond to pioglitazone monotherapy and require additional glycemic control may be initiated at either 15/500 mg twice daily or 15/850 mg once daily, and gradually titrated after assessing adequacy of therapeutic response. Patients switching from combination therapy of pioglitazone plus metformin as separate tablets may be initiated with either the 15/500-mg or 15/850-mg tablet strengths based on the doses of pioglitazone and metformin already being taken.