Rosiglitazone precautions

List of precautions
General Hypoglycemia Edema Macular Edema Hematologic Ovulation Hepatic Effects

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

Hypoglycemia
Patients receiving AVANDIA in combination with other hypoglycemic agents may be at risk for hypoglycemia, and a reduction in the dose of the concomitant agent may be necessary. Return to top

Edema
AVANDIA should be used with caution in patients with edema. In a clinical study in healthy volunteers who received 8 mg of AVANDIA once daily for 8 weeks, there was a statistically significant increase in median plasma volume compared to placebo. Since thiazolidinediones, including rosiglitazone, can cause fluid retention, which can exacerbate or lead to congestive heart failure, AVANDIA should be used with caution in patients at risk for heart failure. Patients should be monitored for signs and symptoms of heart failure. Return to top

Macular Edema
Macular edema has been reported in postmarketing experience in some diabetic patients who were taking AVANDIA or another thiazolidinedione. Some patients presented with blurred vision or decreased visual acuity, but some patients appear to have been diagnosed on routine ophthalmologic examination. Most patients had peripheral edema at the time macular edema was diagnosed. Some patients had improvement in their macular edema after discontinuation of their thiazolidinedione. Patients with diabetes should have regular eye exams by an ophthalmologist, per the Standards of Care of the American Diabetes Association. Additionally, any diabetic who reports any kind of visual symptom should be promptly referred to an ophthalmologist, regardless of the patient’s underlying medications or other physical findings. Return to top

Hematologic
Across all controlled clinical studies in adults, decreases in hemoglobin and hematocrit (mean decreases in individual studies ≤1.0 gram/dL and ≤3.3%, respectively) were observed for AVANDIA alone and in combination with other hypoglycemic agents. The changes occurred primarily during the first 3 months following initiation of therapy with AVANDIA or following a dose increase in AVANDIA. White blood cell counts also decreased slightly in adult patients treated with AVANDIA. Small decreases in hemoglobin and hematocrit have also been reported in pediatric patients treated with AVANDIA. The observed changes may be related to the increased plasma volume observed with treatment with AVANDIA and may be dose related. Return to top

Ovulation
Therapy with AVANDIA, 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 AVANDIA thus, adequate contraception in premenopausal women should be recommended. This possible effect has not been specifically investigated in clinical studies so the frequency of this occurrence is not known. Return to top

Hepatic Effects
Another drug of the thiazolidinedione class, troglitazone, was associated with idiosyncratic hepatotoxicity, and very rare cases of liver failure, liver transplants, and death were reported during clinical use. In pre-approval controlled clinical trials in patients with type 2 diabetes, troglitazone was more frequently associated with clinically significant elevations in liver enzymes (ALT >3X upper limit of normal) compared to placebo. Very rare cases of reversible jaundice were also reported. In postmarketing experience with AVANDIA, reports of hepatitis and of hepatic enzyme elevations to 3 or more times the upper limit of normal have been received. Very rarely, these reports have involved hepatic failure with and without fatal outcome, although causality has not been established. Rosiglitazone is structurally related to troglitazone, a thiazolidinedione no longer marketed in the United States, which was associated with idiosyncratic hepatotoxicity and rare cases of liver failure, liver transplants, and death during clinical use. Pending the availability of the results of additional large, long-term controlled clinical trials and additional postmarketing safety data, it is recommended that patients treated with AVANDIA undergo periodic monitoring of liver enzymes. Return to top