Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

Due to its mechanism of action, rosiglitazone is active only in the presence of endogenous insulin. Therefore, AVANDARYL should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Co-administration with insulin is not recommended.

Elderly patients may be particularly susceptible to hypoglycemic effects.

AVANDARYL is not recommended in patients with symptomatic heart failure. Initiation of AVANDARYL in patients with established NYHA Class III or IV heart failure is contraindicated.

Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients.

Rosiglitazone, like other thiazolidinediones, alone or in combination with other antidiabetic agents, can cause fluid retention, which may exacerbate or lead to heart failure.

Do not initiate if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels.

With sulfonylureas, including glimepiride, there may be an elevation of liver enzyme levels in rare cases. In isolated instances, impairment of liver function (e.g., with cholestasis and jaundice), as well as hepatitis (which may also lead to liver failure) have been reported.

Dose-related weight gain was seen with AVANDARYL, rosiglitazone alone, and rosiglitazone together with other hypoglycemic agents.

In elderly, debilitated, or malnourished patients, or in patients with renal, hepatic, or adrenal insufficiency, the starting dose, dose increments, and maintenance dosage of AVANDARYL should be conservative to avoid hypoglycemic reactions.

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

Long-term trials show an increased incidence of bone fracture in patients, particularly female patients, taking rosiglitazone.

Decreases in hemoglobin and hematocrit occurred in a dose-related fashion in adult patients treated with rosiglitazone.

Sulfonylureas can cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Because glimepiride, a component of AVANDARYL, is a sulfonylurea, use caution in patients with G6PD deficiency and consider the use of a non-sulfonylurea alternative.

An inhibitor of CYP2C8 (e.g., gemfibrozil) may increase the AUC of rosiglitazone and an inducer of CYP2C8 (e.g., rifampin) may decrease the AUC of rosiglitazone. Therefore, if an inhibitor or an inducer of CYP2C8 is started or stopped during treatment with rosiglitazone, changes in diabetes treatment may be needed based upon clinical response.

A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the IV, topical, or vaginal preparations of miconazole is not known. Potential interactions of glimepiride with other drugs metabolized by cytochrome P450 2C9 also include phenytoin, diclofenac, ibuprofen, naproxen, and mefenamic acid.

There may be an interaction between glimepiride and inhibitors (e.g., fluconazole) and inducers (e.g., rifampin) of CYP2C9. Fluconazole may inhibit the metabolism of glimepiride, causing increased plasma concentrations of glimepiride which may lead to hypoglycemia. Rifampin may induce the metabolism of glimepiride, causing decreased plasma concentrations of glimepiride which may lead to worsening glycemic control.

The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including glimepiride, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic 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 AVANDARYL, monitor the patient closely for hypoglycemia. When these medications are withdrawn from a patient receiving AVANDARYL, 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, and terbutaline), and isoniazid. When these medications are administered to a patient receiving AVANDARYL, monitor the patient closely for worsening glycemic control. When these medications are withdrawn from a patient receiving AVANDARYL, monitor the patient closely for hypoglycemia.

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

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

Colesevelam can reduce the maximum plasma concentration and total exposure of glimepiride when the two are coadministered. However, absorption is not reduced when glimepiride is administered 4 hours prior to colesevelam. Therefore, AVANDARYL should be administered at least 4 hours prior to colesevelam.

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

Therapy with rosiglitazone, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. As a result, these patients may be at an increased risk for pregnancy while taking rosiglitazone.

AVANDARYL should not be used during pregnancy or in nursing mothers.

GoToSource

• Dosage greater than 8 mg rosiglitazone and 4 mg glimepiride. GoToSource

• Use in patients under the age of 18. GoToSource

• Type 1 diabetes. GoToSource 

• Carotid intima-media thickness progression in nondiabetic coronary artery disease patients. GoToSource

• Prevention of in-stent restenosis. GoToSource

• Hypertension. GoToSource

• Alzheimer’s disease. GoToSource

• Polycystic ovary syndrome. GoToSource

• Residual or recurrent pituitary adenoma. GoToSource

• Cushing’s syndrome. GoToSource

• HAART-associated lipodystrophy. GoToSource

• Active ulcerative colitis. GoToSource

• Thyroglobulin-positive and radioiodine-negative advanced differentiated thyroid cancer. GoToSource

• Acanthosis nigricans skin lesions. GoToSource

Myocardial infarction. GoToSource 

Heart failure and strokes. GoToSource 

Hip fractures. GoToSource 

Increased risk of bladder cancer with long term use (≥ 5 years). GoToSource 

Diabetic macular edema. GoToSource 

Hypoglycemia (low blood sugar), weight gain, edema (swelling), higher levels of low-density lipoprotein (LDL) cholesterol and decreased hematocrit. GoToSource

Fractures. GoToSource

Lawsuits filed for heart failure.