title: Anti-infectives and the risk of severe hypoglycemia in users of glipizide or glyburide.
abstract: 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.
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania, USA.
authors.forename: H
authors.initials: H
authors.lastname: Schelleman
authors.forename: W B
authors.initials: WB
authors.lastname: Bilker
authors.forename: C M
authors.initials: CM
authors.lastname: Brensinger
authors.forename: F
authors.initials: F
authors.lastname: Wan
authors.forename: S
authors.initials: S
authors.lastname: Hennessy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D018592:Cross-Over Studies; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005006:Ethnicity; D005260:Female; D015725:Fluconazole / Q000009:adverse effects; D005913:Glipizide / Q000009:adverse effects*; D005905:Glyburide / Q000009:adverse effects*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012306:Risk; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D000935:Antifungal Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D015725:Fluconazole; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D005905:Glyburide; D005913:Glipizide