Antibiotic and sulfonylurea reactions may cause serious hypoglycemic events

Hypoglycemia occurred more frequently in patients taking certain antibiotics while on sulfonylureas, a study found.

Researchers conducted a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients age 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. They then compared rates of hypoglycemic events in the 14 days after filling the antimicrobial prescriptions. Results appeared online in JAMA Internal Medicine on Sept. 1.

Compared to those taking antibiotics not expected to interact with sulfonylureas, patients taking clarithromycin had a much higher rate of hypoglycemia (odds ratio [OR], 3.96; 95% CI, 2.42 to 6.49), as did those on levofloxacin (OR, 2.60; 95% CI, 2.18 to 3.10), sulfamethoxazole-trimethoprim (OR, 2.56; 95% CI, 2.12 to 3.10), metronidazole (OR, 2.11; 95% CI, 1.28 to 3.47), and ciprofloxacin (OR, 1.62; 95% CI, 1.33 to 1.97). Antibiotics not expected to interact with sulfonylureas (and used as the reference standard) included amoxicillin, azithromycin, cefdinir, cefuroxime, cephalexin, clindamycin, doxycycline, nitrofurantoin, and penicillin V.

The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. More than a third (39.8%) of the antimicrobial/sulfonylurea hypoglycemic events required hospitalization, and patients who experienced the remainder of the events were treated and released from the emergency department. Nine patients on the interacting drugs died during hospitalization for hypoglycemia, compared to 3 on the noninteracting antimicrobials (P=0.02).

The researchers noted that interactions with some drugs, for example sulfamethoxazole-trimethoprim, have been known for a while, and yet patients on sulfonylureas are still commonly receiving them. The study found that, in 2009, 28.3% of the patients prescribed a sulfonylurea received 1 of the 5 problematic antimicrobials, and these drugs were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The low cost of the drugs may motivate physicians to prescribe them, but the expense of treating hypoglycemia outweighs that cost savings, with excess Medicare payments for the emergency department and hospital treatment of hypoglycemia adding $30.54 per prescription, the authors calculated.

An editorial stated that since polypharmacy has become ubiquitous, better surveillance for drug-drug interactions is needed, and noted that the true costs of hypoglycemia extend beyond immediate treatment. “Serious hypoglycemia substantially lowers health-related quality of life for many patients and, therefore, shifts the balance of benefits and harms,” the editorial said.