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 a sulfonylurea or who have inadequate glycemic control on a thiazolidinedione alone or a sulfonylurea alone.

DUETACT should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with DUETACT or any other antidiabetic drug.

Thiazolidinediones, including pioglitazone, which is a component of DUETACT, cause or exacerbate congestive heart failure in some patients. After initiation of DUETACT and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of DUETACT must be considered.

DUETACT is not recommended in patients with symptomatic heart failure. Initiation of DUETACT in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated.

The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.

DUETACT should be used with caution in patients with edema. Because thiazolidinediones, including pioglitazone, can cause fluid retention, which can exacerbate or lead to congestive heart failure, DUETACT should be used with caution in patients at risk for congestive heart failure.

Therapy with sulfonylureas should be administered cautiously in patients with liver and/or renal disease.

Patients who have serum ALT greater than three times the reference range with serum total bilirubin greater than two times the reference range without alternative etiologies are at risk for severe drug-induced liver injury and should not be restarted on DUETACT. For patients with lesser elevations of serum ALT or bilirubin and with an alternate probable cause, treatment with DUETACT can be used with caution.

Obtain liver tests before starting DUETACT. If abnormal, use caution when treating with DUETACT, investigate the probable cause, treat (if possible) and follow appropriately. Monitoring liver tests while on DUETACT is not recommended in patients without liver disease.

Preclinical and clinical trial data, and results from an observational study suggest an increased risk of bladder cancer in pioglitazone users. The observational data further suggest that the risk increases with duration of use. Consequently, DUETACT should not be used in patients with active bladder cancer and the benefits of glycemic control versus unknown risks for cancer recurrence with DUETACT should be considered in patients with a prior history of bladder cancer.

Macular edema has been reported in postmarketing experience in diabetic patients who were taking pioglitazone or another thiazolidinedione.

There have been postmarketing reports of hypersensitivity reactions in patients treated with glimepiride, a component of DUETACT, including serious reactions such as anaphylaxis, angioedema, and Stevens-Johnson Syndrome.

The risk of fracture should be considered in the care of patients, especially female patients, treated with DUETACT and attention should be given to assessing and maintaining bone health according to current standards of care. The majority of fractures observed in female patients were nonvertebral fractures including lower limb and distal upper limb.

Sulfonylureas can cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Because DUETACT contains glimepiride, which belongs to the class of sulfonylurea agents, use caution in patients with G6PD deficiency and consider the use of a non-sulfonylurea alternative.

Dose-related weight gain occurs when pioglitazone is used alone or in combination with other antidiabetic medications.

Co-administration of pioglitazone and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of pioglitazone is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors. If gemfibrozil or other CYP2C8 inhibitors need to co-administered, patients should switch to individual components of DUETACT because the minimum dose of pioglitazone in DUETACT exceeds 15 mg.

When colesevelam is coadministered with glimepiride, maximum plasma concentration and total exposure to glimepiride is reduced. Therefore, DUETACT should be administered at least four hours prior to colesevelam.

A potential interaction between oral miconazole and sulfonylureas leading to severe hypoglycemia has been reported.

The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including glimepiride, a component of DUETACT, increasing the susceptibility to and/or intensity of hypoglycemia: oral antidiabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors. When these medications are administered to a patient receiving DUETACT, monitor the patient closely for hypoglycemia. When these medications are withdrawn from a patient receiving DUETACT, monitor the patient closely for worsening glycemic control.

The following are examples of medications that may reduce the glucose-lowering effect of sulfonylureas including glimepiride, leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid. When these medications are administered to a patient receiving DUETACT, monitor the patient closely for worsening glycemic control. When these medications are withdrawn from a patient receiving DUETACT, monitor the patient closely for hypoglycemia.

Beta-blockers, clonidine, and reserpine may lead to either potentiation or weakening of DUETACT’s glucose-lowering effect.

Both acute and chronic alcohol intake may potentiate or weaken the glucose lowering action of DUETACT in an unpredictable fashion.

The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.

Neonates of women with gestational diabetes, who are treated with sulfonylureas during pregnancy, may be at increased risk for neonatal intensive care unit admission, and may develop respiratory distress, hypoglycemia, birth injury, and be large for gestational age. Prolonged severe hypoglycemia, lasting 4-10 days, has been reported in neonates born to mothers receiving a sulfonylurea at the time of delivery and has been reported with the use of agents with a prolonged half-life. Observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly.

Because of the potential for DUETACT to cause serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue DUETACT.

GoToSource

• Use in patients under the age of 18. GoToSource

Bladder cancer. GoToSource

Hypoglycemia. (low blood sugar). GoToSource

Edema and heart failure. GoToSource

Vertebral fractures. GoToSource

Macular edema (blood vessels in the retina leaking fluids). GoToSource 

Hemolytic anemia (abnormal breakdown of red blood cells). GoToSource

Anaphylaxis (severe allergic reaction), angioedema (swelling in deep layers of the skin), stevens-johnson syndrome (severe skin reaction), thrombocytopenia (low blood platelet count) and thrombocytopenic purpura (bleeding disorder). GoToSource

Lawsuits filed for bladder cancer, congestive heart failure, fractures and macular edema.