General: Pioglitazone hydrochloride: Pioglitazone exerts its antihyperglycemic effect only in the presence of insulin. Therefore, Pioglitazone plus Glimepiride tablet should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Hypoglycemia: 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.
Cardiovascular: In U.S. placebo-controlled clinical trials that excluded patients with New York Heart Association (NYHA) Class III and IV cardiac status, the incidence of serious cardiac adverse events related to volume expansion was not increased in patients treated with Pioglitazone as monotherapy or in combination with sulfonylureas or metformin vs. placebo-treated patients. In insulin combination studies, a small number of patients with a history of previously existing cardiac developed congestive heart failure when treated with Pioglitazone in combination with insulin. Patients with NYHA Class III and IV cardiac status were not studied in pre-approval Pioglitazone clinical trials. Pioglitazone is not indicated in patients with NYHA Class III or IV cardiac status.
In post marketing experience with Pioglitazone, cases of congestive heart failure have been reported in patients both with and without previously known heart disease.
Edema: In all U.S. clinical trials with Pioglitazone, edema was reported more frequently in patients treated with Pioglitazone than in placebo-treated with Pioglitazone than in placebo-controlled and appears to be dose related. In post marketing experience, reports of initiation or worsening of edema have been received. Pioglitazone plus Glimepiride tablet should be used with caution in patients with edema.
Weight Gain: Dose related weight gain was observed with Pioglitazone alone in combination with other hypoglycemic agents. The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation.
Ovulation: Therapy with Pioglitazone, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. Thus, adequate contraception in premenopausal women should be recommended while taking Pioglitazone plus Glimepiride tablet. This possible effect has not been investigated in clinical studies so the frequency of this occurrence is not known.
Hematologic: Across all clinical studies with Pioglitazone, mean hemoglobin values declined by 2% to 4% in patients treated with Pioglitazone. These changes primarily occurred within the first 4 to 12 weeks of therapy and remained relatively constant thereafter. These changes may be related to increased plasma volume and have rarely been associated with any significant hematologic clinical effects. Pioglitazone plus Glimepiride tablet may cause decreases in hemoglobin and hematocrit.
Hepatic Effects: There was no evidence of drug-induced hepatotoxicity or elevation of LAT levels in the clinical studies.
General: Glimepiride: Hypoglycemia: All sulfonylurea are capable of producing severe hypoglycemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes. Patients with impaired renal function may be more sensitive to the glucose-lowering effect of Glimepiride. A starting dose of 1 mg of Glimepiride once daily followed by appropriate dose titration is recommended in those patients. Debilitated or malnourished patients and those with adrenal, pituitary, or hepatic insufficiency are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs or other sympatholytic agents. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used. Combined use of Glimepiride with insulin or metformin may increase the potential for hypoglycemia.
Loss of control of blood glucose: When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. The effectiveness of any oral hypoglycemic drug, including Pioglitazone plus Glimepiride tablet, in lowering blood glucose to a desired level decreases in many patient over a period of time, which may be due to progression of the severity of the diabetes or to diminished responsiveness to the drug.
Use in Pregnancy & Lactation: Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies, as well as increased neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Pioglitazone plus Glimepiride tablet should not be used during pregnancy unless the potential benefits justify the potential risk to the fetus.
There are no adequate and well-controlled studies in pregnant women with Pioglitazone plus Glimepiride tablet or its individual components. No animal studies have been conducted with the combined products in Pioglitazone plus Glimepiride tablet. The following data are based on findings in studies performed with Pioglitazone and Glimepiride individually.
Use in Children: Safety and effectiveness of Pioglitazone plus Glimepiride tablet in pediatric patients have not been established.
Use in Elderly: Elderly patients are particularly susceptible to hypoglycemic action of glucose-lowering drugs. In elderly, debilitated, or malnourished patients, or in patients with renal and hepatic insufficiency, the initial dosing, dose increments, and maintenance dosage should be conservative based upon blood glucose levels prior to and after initiation of treatment to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs or other sympatholytic agents.