Coadministration of co-trimoxazole with sulfonylureas: hypoglycemia events and pattern of use

J Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):247-54. doi: 10.1093/gerona/glu072. Epub 2014 May 24.


Background: Coadministration of co-trimoxazole with sulfonylureas is reported to increase the risk of hypoglycemia.

Methods: We identified a cohort of Medicare beneficiaries aged 66 years or older who took glyburide or glipizide for diabetes from a 5% national sample of Medicare Part D claims data in 2008 (n = 34,239). We tracked each participant's claims during 2008-2010 for a co-trimoxazole prescription and subsequent emergency room visits for hypoglycemia. Descriptive statistics and logistic regression modeling were used to evaluate hypoglycemia-related emergency room visits after coadministration of co-trimoxazole with sulfonylureas and its utilization patterns in older adults with diabetes.

Results: Sulfonylureas users prescribed co-trimoxazole had a significant higher risk of emergency room visits for hypoglycemia, compared with those prescribed noninteracting antibiotics (odds ratio = 3.89, 95% confidence interval = 2.29-6.60 for glipizide and odds ratio = 3.78, 95% confidence interval = 1.81-7.90 for glyburide with co-trimoxazole, using amoxicillin as the reference). Co-trimoxazole was prescribed to 16.9% of those taking glyburide or glipizide during 2008-2010, varying from 4.0% to 35.9% across U.S. hospital referral regions. Patients with polypharmacy and with more prescribers were more likely to receive co-trimoxazole. Patients with an identifiable primary care physician had 20% lower odds of receiving a co-trimoxazole prescription. Hospital referral regions with more PCPs had lower rates of coadministration of the two drugs (r = -.26, p < 0.001).

Conclusions: Coadministration of co-trimoxazole with sulfonylureas is associated with increased risk of hypoglycemia, compared with noninteracting antibiotics. Such coadministration is prevalent among older diabetic patients in the United States, especially in patients without an identifiable primary care physician.

Keywords: Diabetes; Drug–drug interaction; Hypoglycemia; Medicare; Older adults..

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*
  • Cohort Studies
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / epidemiology
  • Drug Interactions
  • Emergency Service, Hospital / statistics & numerical data
  • Female
  • Glipizide / administration & dosage
  • Glipizide / adverse effects
  • Glyburide / administration & dosage
  • Glyburide / adverse effects
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Male
  • Medicare
  • Polypharmacy
  • Primary Health Care
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects*
  • United States / epidemiology


  • Anti-Infective Agents
  • Hypoglycemic Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Glyburide
  • Glipizide