Fluconazole-Induced Refractory Hypoglycemia in Gliclazide Therapy: A Preventable Interaction
https://doi.org/10.15605/jafes.041.S1
- Author:
Abdul Rahman Ismail
1
;
Nur Aini Eddy Warman
1
Author Information
1. Department of Internal Medicine, Faculty of Medicine, Universiti Teknologi MARA
- Publication Type:Journal Article
- MeSH:
Fluconazole;
Gliclazide;
Hypoglycemia
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):52-
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:Clinically important drug–drug interactions are a
frequently overlooked cause of severe hypoglycemia in
patients with type 2 diabetes mellitus (T2DM). Gliclazide is
primarily metabolized via cytochrome P450 2C9 (CYP2C9),
while fluconazole is a potent inhibitor of this enzyme.1,2
Concomitant administrations markedly increase gliclazide
plasma concentration and prolong its hypoglycemic effect,
substantially increasing the risk of severe and prolonged
hypoglycemia. In some cases of refractory sulfonylureainduced hypoglycemia, octreotide may need to be
considered early.
Case:A 63-year-old Malay female with a 15-year history of T2DM
on maximum-dose gliclazide (320 mg/day) presented
with syncope and recurrent severe hypoglycemia 5 days
after receiving a single oral dose of fluconazole 150 mg
for a superficial fungal skin infection. Her other antidiabetic medications included metformin 1 g twice daily
and vildagliptin 50 mg once daily. Her blood pressure
on presentation was 151/74 mmHg, and her glucose level
was 2.8 mmol/L. Her presentation was compounded by
community-acquired pneumonia and acute kidney injury
(estimated glomerular filtration rate 52 mL/min/1.73 m²).
Biochemical evaluation excluded adrenal insufficiency,
with normal serum cortisol (1,098 µg/dL), serum sodium
(141 mmol/L), and serum potassium (4.6 mmol/L). Thyroid
and liver function tests were normal. Despite repeated boluses of 50% dextrose and continuous infusion of 20%
dextrose, recurrent hypoglycemia persisted for up to 48
hours after discontinuation of gliclazide, with glucose
ranging from 1.7 to 5.1 mmol/L, reflecting prolonged
sulfonylurea activity.
Conclusion:This case highlights a clinically significant yet preventable
interaction between fluconazole and gliclazide, mediated
through CYP2C9 inhibition, resulting in sustained hyperinsulinemic hypoglycemia. Gliclazide should be reduced
or withheld prior to initiating fluconazole, and medication
review should be performed at every consultation.
- Full text:2026073014114081673EP_A060.pdf
