A retrospective study published in The BMJ suggests the possibility of a significant drug interaction between warfarin and the sulfonylureas glipizide and glimepiride.
Taking either of these diabetes drugs in conjunction with warfarin was linked to increased hospitalizations for falls, altered mental state, and insulin shock among patients 65 and older.
Hospital admissions or emergency room visits were nearly 22% higher for patients who were taking warfarin with glipizide or glimepiride, compared to patients taking the diabetes drugs alone.
Clinical references warn doctors of a potential interaction between these drugs, but evidence of it has been thin, according to lead study author John Romley, PhD, of the University of Southern California (USC) in Los Angeles.
He and his colleagues said that, in their study, evidence of the drug-to-drug interaction was clear.
When taken with glipizide or glimepiride, warfarin can intensify their effects and send blood sugar levels crashing. Patients experiencing hypoglycemia may seem drunk, lightheaded, and confused, and are at risk of falling.
“The take-home message is simply that an interaction can occur that has clinical significance, so providers need to be aware in order to prevent a low blood sugar issue from occurring,” said Anne Peters, MD, also of USC.
“Sometimes this means having the patient monitor their blood sugar levels more often. There are many ways to deal with the issue if one is forewarned.”
Pharmacists don’t need to change patient instructions, added Bradley Williams, PharmD, of USC.
“What it does require is for pharmacists and other clinicians to be more vigilant when a sulfonylurea is added to a regimen that includes warfarin, as well as when a patient who is taking both has a change in their medical status,” Dr Williams said.
“I think additional research into the potential interactions between medications for diabetes and warfarin, as well as other drugs that affect blood clotting, is warranted because of the potential consequences of excessive bleeding.”
For the current study, the researchers analyzed a random sample of 465,918 Medicare beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011. About 15% of these patients (n=71,895) also filled a prescription for warfarin.
The researchers found that hospital admissions or emergency department visits for hypoglycemia were more common with concurrent warfarin and glipizide/glimepiride use than with glipizide/glimepiride use alone. The adjusted odds ratio (AOR) was 1.22.
The risk of hypoglycemia associated with concurrent use was higher among patients taking warfarin for the first time, as well as in patients ages 65 to 74.
Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visits for fall-related fractures (AOR=1.47) and altered consciousness/mental status (AOR=1.22).
The researchers said these findings may not be generalizable beyond the elderly Medicare population.
They also noted that their findings could be confounded by some unmeasured characteristics in patients that may be connected to warfarin use or a risk for hypoglycemia. Another limitation of this study is that the researchers did not measure drug use directly.
