Hypoglycemia After Antimicrobial Drug Prescription for Older Patients Using Sulfonylureas

Abstract

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 PARTICIPANTSThis 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 MEASURESAny hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure. RESULTSIn 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,), 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.

Clinically and pharmacologically relevant interactions of antidiabetic drugs

“…This is even more important, when drugs are used temporarily, for example in case of antimicrobial treatment. Many antibiotic drugs affect hepatic enzyme activity and thus substantially increase hypoglycemic risk with SU, and are associated with higher morbidity and increased costs [Parekh et al 2014]. Thus, interactions due to CYP2C9 inhibition play a crucial role in the treatment with SUs.…”

“…Beta blockers can mask the early warning symptoms of hypoglycemia; however, later studies have shown that these effects may be less prominent with newer beta-1 selective drugs [Shorr et al 1997]. As mentioned earlier, many antimicrobials present a high interaction risk with antidiabetics, especially with Sulfonylureas [Tirkkonen et al 2010, Parekh et al 2014. Interactions with antimicrobials are clinically most relevant because adverse effects take place most often whenever a drug is added or removed [Patsalos et al 2003], and antimicrobials are usually taken temporarily.…”

“…Besides specific pharmacokinetic interactions, which depend on drug metabolism, there are some antibiotics with glucose lowering effects and thus bearing the risk of pharmacodynamic interactions with antidiabetic drugs in general. A clinically relevant example are fluoroquinolones [Chou et al 2013, Fusco et al 2013, Parekh et al 2014. Quinolones seem to have an insulinotropic effect by increasing the release of insulin via a blockade of ATP-sensitive K+ channels in a dose-dependent manner [Maeda et al 1996].…”

Impact of drugs on hypoglycaemia in hospitalised patients

“…Hypoglycaemia induced by polymedication can be explained, in part, by the increased risk of drug interactions. For example, co-prescription of sulfonylureas and quinolones or sulfamethoxazole–trimethoprim were associated with hypoglycaemia in elderly patients,36 as well as non-cardioselective β-blockers by masking hypoglycaemia symptoms during insulin therapy 37. In our cohort, no specific interaction was found to be associated with hypoglycaemia, explained in part by the broad range of different drugs and thus reducing statistical power.…”

Antimicrobial treatment of bacterial infections in frail elderly patients: the difficult balance between efficacy, safety and tolerability

“…A retrospective cohort study of Texas Medicare claims from 2006 and 2009 for older patients who were co-prescribed sulfanylureas with one of the most commonly used antimicrobials assessed the risk of hospitalization or emergency department visit owing to hypoglycaemia within 14 days of antimicrobial exposure. Multivariate analyses showed that the risk of hypoglycaemia varied according to the type of antimicrobial administered and was higher with clarithromycin (OR 3.96; 95% CI 2.42-6.49), levofloxacin (OR 2.60; 95% CI 2.18-3.10), trimethoprim/sulfamethoxazole (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) compared with a panel of non-interacting antimicrobials (amoxicillin, azithromycin, cefdinir, cefuroxime, cephalexin, clindamycin, doxycicline, nitrofurantoin and penicillin V) [34 ]. Likewise, a population-based inception cohort study assessed the risk of hospitalization or emergency department visit owing to dysglycemia within 30 days of antimicrobial exposure among diabetic outpatients who were new users of fluoroquinolones, macrolides or cephalosporins.…”