A Case of Non-Insulin-Dependent Diabetes Mellitus with Hypoglycemia Induced by Miconazole during Treatment with Gliclazide

Abstract

We encountered a 76-year-old female diabetic patient who developed hypoglycemia induced by miconazole during treatment with gliclazide. She was diagnosed as having diabetes mellitus at the age of 55 years. She had been treated with gliclazide in our department for 5 years. On admission she had proliferative retinopathy and proteinuria. A chest x-ray taken in September 1992 revealed a tumor shadow with air-fluid level in the right upper lung. After being admitted, 400 mg of miconazole was administered intravenously during treatment with 40 mg of gliclazide. Five days later the patient developed hypoglycemia. Her blood glucose levels ranged from 30 mg/d/ to 40 mg/d/ in spite of glucose infusion. Two days after gliclazide was discontinued, fasting blood glucose was 36 mg/d/, and serum IRI and CPR were 13.5 μU/m/ and 4.1 ng/m/, respectively. These findings suggested possibility of insulin hypersercretion. There was no evidence of insulinoma on ultrasound and CT examination of the abdomen. We therefore determined the serum concentrations of gliclazide. The serum gliclazide level during hypoglycemia (36 mg/d/) increased to 4.6 pg/m/ in spite of discontinuation of gliclazide two days earlier, whereas the fasting level of gliclazide on admission was 0.2 pg/mi. These results suggest that the hypoglycemia may have been caused by the higher serum gliclazide concentration resulting from an interaction between miconazole and gliclazide.
Miconazole may interfere with gliclazide metabolism by inhibiting the hepatic cytochrome P450 enzyme system. Imidazole antifungal agents, including miconazole, must be used carefully during treatment with oral hypoglycemic agents.