In July 2018, the US Food and Drug Administration (FDA) issued a Drug Safety Communication to alert healthcare professionals and patients about the increased risks for hypoglycemic coma and adverse psychiatric events associated with the use of fluoroquinolone (FQ) antibiotics. Prior to this safety announcement, labeling for individual fluoroquinolone agents differed in regard to warnings and precautions for blood sugar– or mental health–related side effects. The FDA’s intention is to make information pertaining to such side effects more prominent and consistent across the drug class so that healthcare providers and patients can make informed risk-benefit decisions.
The updated labeling for all systemic (oral and injectable) fluoroquinolones resulted from analyses of postmarketing adverse events identified through both the voluntary FDA Adverse Event Reporting System (FAERS) and published medical literature. The FDA’s analyses included safety reports for five FQs: ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin. Delafloxacin, approved in June 2017, was not included, although it is expected to exhibit a similar adverse effect profile and is included in the required labeling updates.
Between October 1987 and April 2017, FAERS received 56 reports of hypoglycemic coma following fluoroquinolone use. Additionally, investigators identified 11 published case reports linking the drug class to hypoglycemic coma. Most cases involved elderly patients or those with renal impairment or diabetes. Among the 47 patients who were receiving concomitant hypoglycemic therapy for diabetes, 35 were receiving a sulfonylurea. However, nearly one third of the reported cases involved patients who were neither diagnosed with diabetes nor receiving hypoglycemic therapy. Of the 67 total cases, the FDA reports that nine patients experienced permanent disability and 13 patients ultimately died as a result of severe hypoglycemia. The FDA investigators noted that renal insufficiency may have complicated these more severe cases. On the basis of the FDA’s review, manufacturer labeling of fluoroquinolones will now include strengthened warnings in the Warnings and Precautions section to explicitly describe the risk for coma due to hypoglycemia.
Adverse Psychiatric Effects
Postmarketing analyses using FAERS and published medical literature related to adverse psychiatric effects also warranted updated fluoroquinolone labeling, according to the FDA. While warning labels for central nervous system (CNS) effects differed across the class, many already included warnings for anxiety, confusion, depression, hallucination, and psychoses. To standardize class-wide labeling, the following six adverse effects will now be included separately in the Warnings and Precautions section: agitation, delirium, disorientation, disturbance in attention, memory impairment, and nervousness. The FDA does not provide qualitative evidence from their analyses but states that these effects have been observed after as little as one fluoroquinolone dose.