How do the most recently identified safety issues affect fluoroquinolones' place in therapy? 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.[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.[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.[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.[1] 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. Recently published evidence supports the FDA's safety alert. A meta-analysis[trimethoprim/sulfamethoxazole (TMP/SMX), cefuroxime, amoxicillin/clavulanic acid, or placebo as comparators, oral fluoroquinolones were associated with 40% greater odds of adverse CNS effects (odds ratio, 1.40; 95% confidence interval, 1.12-1.75). Adverse effects described in the included studies were less severe in nature (eg, tremor, dizziness, insomnia, asthenia) than those being added to the drug labels but provide supporting evidence for an association between fluoroquinolone and CNS outcomes nonetheless. The risks for serious hypoglycemic or psychiatric adverse effects should be carefully weighed against the therapeutic benefits of fluoroquinolones for all patients. Oral and injectable fluoroquinolones should be used cautiously in elderly patients and those with renal impairment owing to an increased risk for drug accumulation, and in patients with diabetes or those who are taking hypoglycemic agents owing to the risk for severe hypoglycemia. Alternative treatment options should be used, when available, for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, or uncomplicated urinary tract infections. For example, amoxicillin/clavulanate is preferred over respiratory fluoroquinolones by the Infectious Diseases Society of America (IDSA) as first-line therapy of acute bacterial sinusitis.[nitrofurantoin are acceptable options for uncomplicated urinary tract infections, per the IDSA and European Society for Microbiology and Infectious Diseases.[headache, and sweating, which can progress to seizures or coma if not treated appropriately. Patients should be told to consider keeping glucose tablets or gel, hard candy, or raisins on hand during fluoroquinolone therapy. Patients with a very high hypoglycemia risk and a prescription for glucagon should keep glucagon with them at all times, and their family members and friends should be comfortable with its administration. If serious hypoglycemic or CNS adverse effects occur during fluoroquinolone therapy, the drug should be immediately discontinued, and an alternative agent should be initiated. The FDA encourages healthcare professionals and patients to report any adverse effects to MedWatch and FAERS.[1] The Bottom Line Rare but serious disturbances in blood glucose and CNS adverse effects are the latest additions to the developing fluoroquinolone safety profile, following warnings for potentially permanent, disabling tendon, muscle, joint, or nerve damage; rare, but serious peripheral neuropathy; and QT interval prolongation. As available evidence of severe adverse effects continues to develop, healthcare providers should use this information to inform safe fluoroquinolone prescribing. Source
