Anti-infectives and the risk of severe hypoglycemia in users of glipizide or glyburide

• Published in: Clinical pharmacology and therapeutics Vol. 88; no. 2; p. 214
• Main Authors: Schelleman, H, Bilker, W B, Brensinger, C M, Wan, F, Hennessy, S
• Format: Journal Article
• Language: English
• Published: United States 01.08.2010
• Subjects: Adolescent; Adult; Aged; Anti-Infective Agents - therapeutic use; Antifungal Agents - adverse effects; Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors; Aryl Hydrocarbon Hydroxylases - metabolism; Blood Glucose - metabolism; Case-Control Studies; Cross-Over Studies; Cytochrome P-450 CYP2C9; Drug Interactions; Enzyme Inhibitors - pharmacology; Ethnic Groups; Female; Fluconazole - adverse effects; Glipizide - adverse effects; Glyburide - adverse effects; Humans; Hypoglycemia - chemically induced; Hypoglycemia - epidemiology; Hypoglycemic Agents - adverse effects; Male; Middle Aged; Risk; Trimethoprim, Sulfamethoxazole Drug Combination - adverse effects; Young Adult
• ISSN: 1532-6535
• DOI: 10.1038/clpt.2010.74

The objective of this study was to evaluate whether orally administered anti-infectives increase the risk of severe hypoglycemia in users of glipizide or glyburide. We performed two case-control studies and two case-crossover studies using US Medicaid data. All the anti-infectives examined were associated with an elevated risk of severe hypoglycemia. Using cephalexin as the reference category, in glipizide users, statistically significant associations were found with co-trimoxazole (odds ratio (OR) = 3.14; 95% confidence interval (CI): 1.83-5.37); clarithromycin (OR = 2.90; 95% CI: 1.69-4.98); fluconazole (OR = 2.53; 95% CI: 1.23-5.23); and levofloxacin (OR = 2.09; 95% CI: 1.35-3.25). In glyburide users, with cephalexin as the reference, statistically significant associations were found with clarithromycin (OR = 5.02; 95% CI: 3.35-7.54); levofloxacin (OR = 2.83; 95% CI: 1.73-4.62); co-trimoxazole (OR = 2.68; 95% CI: 1.59-4.52); fluconazole (OR = 2.20; 95% CI: 1.04-4.68); and ciprofloxacin (OR = 2.08; 95% CI: 1.23-3.52). In conclusion, exposure to all studied anti-infective agents were associated with subsequent severe hypoglycemia. Using cephalexin as the reference, drug-drug interactions were evident with ciprofloxacin (in glyburide users only), clarithromycin, co-trimoxazole, fluconazole, and levofloxacin.