Drugs Metabolized by Cytochrome P450
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. [See Clinical Pharmacology .]
Although drug interactions for metformin with cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of AVANDAMET and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system. [See Warnings and Precautions Clinical Pharmacology (12.4).]
Drugs That Produce Hyperglycemia
When drugs that produce hyperglycemia, which may lead to loss of glycemic control, are administered to a patient receiving AVANDAMET, the patient should be closely observed to maintain adequate glycemic control. [See Clinical Pharmacology .]
Limited data are available with regard to overdosage in humans. In clinical trials in volunteers, rosiglitazone has been administered at single oral doses of up to 20 mg and was well tolerated. In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s clinical status.
Hypoglycemia has not been seen with ingestion of up to 85 grams of metformin, although lactic acidosis has occurred in such circumstances [see Warnings and Precautions]. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated metformin from patients in whom metformin overdosage is suspected.
•Initiation in patients with established New York Heart Association (NYHA) Class III or IV heart failure [see Boxed Warning].
•Use in patients with renal disease or renal dysfunction [e.g., as suggested by serum creatinine levels ≥1.5 mg/dL (males), ≥1.4 mg/dL (females), or abnormal creatinine clearance], which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia [see Warnings and Precautions].
•Use in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
•Use in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. AVANDAMET should be temporarily discontinued in these patients. [See Warnings and Precautions .]
Use in patients with a history of a hypersensitivity reaction to rosiglitazone or any of the product’s ingredients.