Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas

JAMA Intern Med. 2014 Oct;174(10):1605-12. doi: 10.1001/jamainternmed.2014.3293.


Importance: Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia.

Objective: To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug.

Design, setting, and participants: This was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population.

Methods: We assessed hypoglycemia events and associated Medicare costs in patients prescribed 1 of 7 antimicrobial agents thought to interact with sulfonylureas, using noninteracting antimicrobials as a comparison. We used a repeated measure logistic regression, controlling for age, sex, ethnicity, Medicaid eligibility, comorbidity, prior emergency department visits for hypoglycemia, prior hospitalizations for any cause, nursing home residence, and indication for the antimicrobial. We estimated odds of hypoglycemia, number needed to harm, deaths during hospitalization for hypoglycemia, and Medicare costs for hypoglycemia treatment.

Main outcomes and measures: Any hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure.

Results: In multivariable analyses controlling for patient characteristics and indication for antimicrobial drug use, clarithromycin (odds ratio [OR], 3.96 [95% CI, 2.42-6.49]), levofloxacin (OR, 2.60 [95% CI, 2.18-3.10]), sulfamethoxazole-trimethoprim (OR, 2.56 [95% CI, 2.12-3.10]), metronidazole (OR, 2.11 [95% CI, 1.28-3.47]), and ciprofloxacin (OR, 1.62 [95% CI, 1.33-1.97]) were associated with higher rates of hypoglycemia compared with a panel of noninteracting antimicrobials. The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Patient factors associated with hypoglycemia included older age, female sex, black or Hispanic race/ethnicity, higher comorbidity, and prior hypoglycemic episode. In 2009, 28.3% of patients prescribed a sulfonylurea filled a prescription for 1 of these 5 antimicrobials, which were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The treatment of subsequent hypoglycemia adds $30.54 in additional Medicare costs to each prescription of 1 of those 5 antimicrobials given to patients taking sulfonylureas.

Conclusions and relevance: Prescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / adverse effects*
  • Ciprofloxacin / adverse effects
  • Clarithromycin / adverse effects
  • Drug Interactions
  • Drug Prescriptions
  • Female
  • Glipizide / adverse effects
  • Glyburide / adverse effects
  • Health Care Costs
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemia / economics*
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Levofloxacin / adverse effects
  • Logistic Models
  • Male
  • Medicare
  • Metronidazole / adverse effects
  • Morbidity
  • Odds Ratio
  • Retrospective Studies
  • Risk Factors
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / adverse effects*
  • Texas
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
  • United States / epidemiology


  • Anti-Infective Agents
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Metronidazole
  • Ciprofloxacin
  • Levofloxacin
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Clarithromycin
  • Glyburide
  • Glipizide