AVANDAMET 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 metformin therapy is appropriate.

Management of type 2 diabetes mellitus 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 or escalation of oral antidiabetic therapy in patients with type 2 diabetes mellitus, secondary causes of poor glycemic control, e.g., infection, should be investigated and treated.

General

The dosage of antidiabetic therapy with AVANDAMET should be individualized on the basis of effectiveness and tolerability while not exceeding the maximum recommended daily dose of 8 mg/2,000 mg. The risk-benefit of initiating monotherapy versus dual therapy with AVANDAMET should be considered. (See CLINICAL TRIALS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS.)

All patients should start the rosiglitazone component of AVANDAMET at the lowest recommended dose. 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 maleate).

AVANDAMET is generally given in divided doses with meals, with gradual dose escalation. This reduces gastrointestinal side effects (largely due to metformin) and permits determination of the minimum effective dose for the individual patient.

Sufficient time should be given to assess adequacy of therapeutic response. Fasting plasma glucose (FPG) should be used to determine the therapeutic response to AVANDAMET.

AVANDAMET in Drug-Na ve Patients

The recommended starting dose of AVANDAMET is 2 mg/500 mg administered once or twice daily. For patients with HbA1c > 11% or FPG > 270 mg/dL, a starting dose of 2 mg/500 mg twice daily may be considered. The dose of AVANDAMET may be increased in increments of 2 mg/500 mg per day to a maximum of 8 mg/2,000 mg per day given in divided doses if patients are not adequately controlled after 4 weeks.

AVANDAMET in Patients Inadequately Controlled with Rosiglitazone or Metformin Monotherapy

The selection of the dose of AVANDAMET in patients treated with rosiglitazone and/or metformin therapy should be based on the patient's current doses of rosiglitazone and/or metformin. After an increase in metformin dosage, dose titration is recommended if patients are not adequately controlled after 1 to 2 weeks. After an increase in rosiglitazone dosage, dose titration is recommended if patients are not adequately controlled after 8 to 12 weeks.

For patients inadequately controlled on metformin monotherapy, the usual starting dose of AVANDAMET is 4 mg rosiglitazone (total daily dose) plus the dose of metformin already being taken (see Table 10).

For patients inadequately controlled on rosiglitazone monotherapy, the usual starting dose of AVANDAMET is 1,000 mg metformin (total daily dose) plus the dose of rosiglitazone already being taken (see Table 10).

When switching from combination therapy of rosiglitazone plus metformin as separate tablets, the usual starting dose of AVANDAMET is the dose of rosiglitazone and metformin already being taken.

If additional glycemic control is needed, the daily dose of AVANDAMET may be increased by increments of 4 mg rosiglitazone and/or 500 mg metformin, up to the maximum recommended total daily dose of 8 mg/2,000 mg.

Table 10. AVANDAMET Starting Dose for Patients Treated with Metformin and/or
Rosiglitazone

Specific Patient Populations

Pregnancy

AVANDAMET is not recommended for use in pregnancy.

Geriatric

The initial and maintenance dosing of AVANDAMET should be conservative in patients with advanced age, due to the potential for decreased renal function in this population.

Renal Impairment

Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of AVANDAMET. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly (see WARNINGS).

Hepatic Impairment

Therapy with AVANDAMET 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 AVANDAMET and periodically thereafter (see PRECAUTIONS, Hepatic Effects).

Pediatric

Safety and effectiveness of AVANDAMET in pediatric patients have not been established. AVANDAMET and rosiglitazone are not indicated for use in pediatric patients.

Tablets: Each tablet contains rosiglitazone as the maleate and metformin hydrochloride as follows:

2 mg/500 mg – pale pink, film-coated oval tablet, debossed with gsk on one side and 2/500 on the other.

4 mg/500 mg – orange, film-coated oval tablet, debossed with gsk on one side and 4/500 on the other.

2 mg/1,000 mg – yellow, film-coated oval tablet, debossed with gsk on one side and 2/1000 on the other.

4 mg/1,000 mg – pink, film-coated oval tablet, debossed with gsk on one side and 4/1000 on the other.

2 mg/500 mg bottles of 60: NDC 0007-3167-18

4 mg/500 mg bottles of 60: NDC 0007-3168-18

2 mg/1,000 mg bottles of 60: NDC 0007-3163-18

4 mg/1,000 mg bottles of 60: NDC 0007-3164-18

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.

GLUCOPHAGE is a registered trademark of Merck Santé S.A.S., an associate of Merck KGaA of Darmstadt, Germany. Licensed to Bristol-Myers Squibb Company. AVANDAMET is a registered trademark of GlaxoSmithKline.
GlaxoSmithKline., Research Triangle Park, NC 27709. August 2007. FDA rev date: 8/21/2007

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