Pioglitazone exerts its antihyperglycemic effect only in the presence of insulin. Therefore, Pioglitazone should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Pioglitazone should be used with caution in combination especially with insulin, hepatic insufficiency and heart diseases.
Metformin is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus patients with serum creatinine levels above the upper limit of normal for their age should not receive this combination.
Dosage of this preparation must be individualized on the basis of effectiveness and tolerability while not exceeding the maximum recommended daily dose of Pioglitazone 45 mg and Metformin 2550 mg.
It may be initiated at either the 15 mg/500 mg twice daily or 15 mg/850 mg once daily with meals to reduce the gastrointestinal side effects associated with Metformin and gradually titrated after assessing adequacy of therapeutic response.
The initial and maintenance dose of it should be carefully selected in patients with advanced age due to the potential for decreased renal function in these populations.
Monitoring of renal function is necessary to aid in prevention of Metformin associated lactic acidosis, particularly in the elderly. It should not be initiated if the patients exhibit clinical evidence of active liver disease. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with combination of Pioglitazone and Metformin and periodically thereafter.