Avandamet - Warnings & Precautions

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In a double-blind study in type 2 diabetes patients with chronic renal failure (112 received 4 mg or 8 mg of rosiglitazone plus insulin and 108 received insulin alone), there was no difference in cardiovascular adverse events with rosiglitazone in combination with insulin compared to insulin alone.

Patients treated with combination AVANDAMET and insulin should be monitored for cardiovascular adverse events. The combination therapy should be discontinued in patients who do not respond as manifested by a reduction in HbA1c or insulin dose after 4 to 5 months of therapy or who develop any significant adverse events. (See ADVERSE REACTIONS.) There are no studies that have evaluated the safety or effectiveness of AVANDAMET in combination with insulin. The use of AVANDAMET in combination with insulin is not indicated.

PRECAUTIONS

General

Metformin hydrochloride

Monitoring of renal function:

Metformin is known to be substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive AVANDAMET. In patients with advanced age, AVANDAMET should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, particularly those 80 years of age, renal function should be monitored regularly and, generally, AVANDAMET should not be titrated to the maximum dose of the metformin component, i. e., 2,000 mg (see WARNINGS and DOSAGE AND ADMINISTRATION).

Before initiation of therapy with AVANDAMET and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and AVANDAMET discontinued if evidence of renal impairment is present. Use of concomitant medications that may affect renal function or metformin disposition: Concomitant medication( s) that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion (see PRECAUTIONS, Drug Interactions), should be used with caution.