Several antibiotics tied to hypoglycemia in patients on sulfonylureas

By Will Boggs MD

NEW YORK (Reuters Health) - Use of certain antimicrobial agents is linked with an increased risk of hypoglycemia in older patients on sulfonylureas, according to a study of Medicare claims.

"Physicians should definitely avoid using those antibiotics in patients on sulfonylureas," Dr. James S. Goodwin from University of Texas Medical Branch in Galveston told Reuters Health by email. "In the great majority of cases, there are equally effective, noninteracting antibiotics available."

Other investigators have documented increased hospitalizations for hypoglycemia with these sulfonylureas following coadministration of several antimicrobial agents, Dr. Goodwin's team writes in JAMA Internal Medicine, online September 1.

The researchers used data from Texas Medicare beneficiaries to estimate the proportion of all hypoglycemic events in patients prescribed glipizide or glyburide that were attributed to an interacting antibiotic and to estimate the downstream Medicare costs associated with these events.

The rate of hypoglycemic episodes varied from 0.17% to 1.44% in glipizide users and from 0.32% to 1.87% in glyburide users after treatment with one of 16 antimicrobials included in the study.

Among the antimicrobials investigated, ciprofloxacin, clarithromycin, levofloxacin, metronidazole, and sulfamethoxazole-trimethoprim were significantly associated with hypoglycemia, the researchers found.

The number needed to harm ranged from 71 prescriptions for clarithromycin to 334 for ciprofloxacin.

Moxifloxacin and fluconazole, two antimicrobials previously suggested to have an association with hypoglycemia, were not significantly associated with hypoglycemia in this study.

Compared with the noninteracting antimicrobials, the excess Medicare payments for the treatment of hypoglycemia after prescription of one of the five antimicrobials was $30.54 per prescription, which totaled about $2.1 million in additional Medicare costs for the nearly 70,000 antimicrobial prescriptions that overlapped with a sulfonylurea.

"In addition, antibiotics tend to be overprescribed in the community, so often the best choice is not to prescribe one," Dr. Goodwin said. "Some physicians may have the attitude 'well, it can't hurt' when prescribing an antibiotic. Our study is an example of one of the many ways such drugs can hurt."

"To enhance safe prescribing, clinicians and patients need to carefully consider the expected benefits and harms of glucose-lowering agents, in the context of each patient's values and preferences," Dr. Kasia J. Lipska from Yale School of Medicine, New Haven, Connecticut writes in a linked commentary in the journal. "Serious hypoglycemia substantially lowers health-related quality of life for many patients and, therefore, shifts the balance of benefits and harms."

Dr. Gerry Rayman from The Ipswich Hospital NHS Trust in the UK, who was not involved in the new work, has looked at the burden of sulfonylurea-related hypoglycemia in UK hospitals.

He told Reuters Health by email that doctors should avoid prescribing these antibiotics for diabetics taking sulfonylureas "if an alternative non-interfering antibiotic could be used. If not, the patient should be advised to monitor their glucose levels more frequently and reduce the dose if their glucose results fall. Those who already have tight control should perhaps have the dose reduced from the onset of therapy."

"This is a significant cause of morbidity and cost (deaths although 3 times as frequent were actually low considering the large numbers of hypoglycemic episodes) and must be considered when prescribing these antibiotics," Dr. Rayman said.

"Since the paper only includes ER attendance and hospitalization the number of minor hypoglycemias not requiring hospital attendance is likely to be considerable," he added.

Dr. Sean Hennessy from the University of Pennsylvania School of Medicine in Philadelphia, who has conducted similar research, said diabetic patients who develop infections need close monitoring, both for hypo- and hyperglycemia.

"A reasonable recommendation would be to increase the frequency of fingerstick blood glucose measurements in patients who self-monitor, and consideration of laboratory glucose monitoring in patients who don't," he told Reuters Health by email. "Also, antibiotics with particularly high risks (like trimethoprim-sulfamethoxazole) should be avoided in favor of antibiotics with less risk."

SOURCE: https://bit.ly/1qzTvRj and https://bit.ly/1CtTRzc

JAMA Intern Med 2014.

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