Avandaryl (Rosiglitazone Maleate / Glimepiride) - Indications and Dosage

INDICATIONS AND USAGE

AVANDARYL is indicated as an adjunct to diet and exercise, to improve glycemic control in patients with type 2 diabetes mellitus when treatment with dual rosiglitazone and glimepiride therapy is appropriate.

Management of type 2 diabetes should include diet control. Caloric restriction, weight loss, and exercise are essential for the proper treatment of the diabetic patient because they help improve insulin sensitivity. This is important not only in the primary treatment of type 2 diabetes, but also in maintaining the efficacy of drug therapy. Prior to initiation of therapy with AVANDARYL, secondary causes of poor glycemic control, e.g., infection, should be investigated and treated.

DOSAGE AND ADMINISTRATION

• AVANDARYL is available for oral administration as tablets containing rosiglitazone maleate and glimepiride, respectively, in the following strengths (expressed as rosiglitazone maleate/glimepiride): 4 mg/1 mg, 4 mg/2 mg, 4 mg/4 mg, 8 mg/2 mg, and 8 mg/4 mg.
• AVANDARYL should be given once daily with the first meal of the day. If a dose is forgotten, the following dose must not be doubled.
• Therapy with AVANDARYL should be individualized for each patient. The risk-benefit of initiating monotherapy versus dual therapy with AVANDARYL should be considered. (See CLINICAL TRIALS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS.)

Starting Dose

• The recommended starting dose is 4 mg/1 mg administered once daily with the first meal of the day. For patients already treated with a sulfonylurea or a thiazolidinedione, a starting dose of 4 mg/2 mg may be considered.
• When switching from combination therapy of rosiglitazone plus glimepiride as separate tablets, the usual starting dose of AVANDARYL is the dose of rosiglitazone and glimepiride already being taken.

Dose Titration

• Dose increases should be individualized according to the glycemic response of the patient.
• Patients who may be more sensitive to glimepiride (see PRECAUTIONS, Hypoglycemia), including the elderly, debilitated, or malnourished, and those with renal, hepatic, or adrenal insufficiency, should be carefully titrated to avoid hypoglycemia.
• If hypoglycemia occurs during up-titration of the dose or while maintained on therapy, a dosage reduction of the glimepiride component of AVANDARYL may be considered.
• For patients previously treated with thiazolidinedione monotherapy and switched to AVANDARYL, dose titration of the glimepiride component of AVANDARYL is recommended if patients are not adequately controlled after 1 to 2 weeks.
• Increases in glimepiride component: The glimepiride component may be increased in no more than 2 mg increments. After an increase in the dosage of the glimepiride component, dose titration of AVANDARYL is recommended if patients are not adequately controlled after 1 to 2 weeks.
• For patients previously treated with sulfonylurea monotherapy and switched to AVANDARYL, it may take 2 weeks to see a reduction in blood glucose and 2 to 3 months to see the full effect of the rosiglitazone component. Therefore, dose titration of the rosiglitazone component of AVANDARYL is recommended if patients are not adequately controlled after 8 to 12 weeks. Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to AVANDARYL due to potential overlapping of drug effect.
• Increases in rosiglitazone component: After an increase in the dosage of the rosiglitazone component, dose titration of AVANDARYL is recommended if patients are not adequately controlled after 2 to 3 months. Further increases in the dose of rosiglitazone should be accompanied by careful monitoring for adverse events related to fluid retention (see BOXED WARNING and WARNINGS, Rosiglitazone).

Maximum Dose

• The maximum recommended daily dose is 8 mg rosiglitazone/4 mg glimepiride.

No studies have been performed specifically examining the safety and efficacy of AVANDARYL in patients previously treated with other oral hypoglycemic agents and switched to AVANDARYL. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur. (See INDICATIONS AND USAGE.)

Specific Patient Populations

• Pregnancy and Lactation: AVANDARYL should not be used during pregnancy or in nursing mothers.
• Pediatric Use: Safety and effectiveness of AVANDARYL in pediatric patients have not been established. AVANDARYL and its components, rosiglitazone and glimepiride, are not indicated for use in pediatric patients.
• Elderly and Malnourished Patients and those with Renal, Hepatic, or Adrenal Insufficiency: 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. (See CLINICAL PHARMACOLOGY, Special Populations, and PRECAUTIONS, Hypoglycemia.)
• Hepatic Impairment: Therapy with AVANDARYL should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5X upper limit of normal at start of therapy) (see PRECAUTIONS, Hepatic Effects and CLINICAL PHARMACOLOGY, Special Populations, Hepatic Impairment). Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with AVANDARYL and periodically thereafter (see PRECAUTIONS, Hepatic Effects).

HOW SUPPLIED

Tablets: Each tablet contains rosiglitazone as the maleate and glimepiride as follows:

4 mg/1 mg − yellow, rounded triangular tablet, gsk debossed on one side and 4/1 on the other.

4 mg/2 mg− orange, rounded triangular tablet, gsk debossed on one side and 4/2 on the other.

4 mg/4 mg − pink, rounded triangular tablet, gsk debossed on one side and 4/4 on the other.

8 mg/2 mg – pale pink, rounded triangular tablet, gsk debossed on one side and 8/2 on the other.

8 mg/4 mg – red, rounded triangular tablet, gsk debossed on one side and 8/4 on the other.

4 mg/1 mg bottles of 30: NDC 0007-3151-13

4 mg/2 mg bottles of 30: NDC 0007-3152-13

4 mg/4 mg bottles of 30: NDC 0007-3153-13

8 mg/2 mg bottles of 30: NDC 0007-3148-13

8 mg/4 mg bottles of 30: NDC 0007-3149-13

STORAGE

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Dispense in a tight, light-resistant container.