A Reappraisal of Ciprofloxacin Use in Infants and Children

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS


Pediatr Pharm. 2018;24(8) 

In This Article

FDA Drug Safety Communications

The first drug safety communication on fluoroquinolone adverse effects was issued a decade ago.[1] In July 2008, the FDA announced the addition of a black box warning to all fluoroquinolones alerting prescribers to the increased risk for tendinitis and tendon rupture during treatment. Two years later, a second drug safety communication was published highlighting an addition to the black box warning regarding reports of worsening symptoms in patients with myasthenia gravis treated with drugs in this therapeutic class. In 2013, this labeling change was again updated to include the risk for irreversible peripheral neuropathy.

In November 2015, an FDA Advisory Committee met to discuss the risks and benefits of fluoroquinolones in the routine treatment of acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, and uncomplicated UTIs.[16] The committee concluded that the risk for serious adverse effects outweighed the benefit in these infections and recommended that labeling reflect this information. On May 12, 2016, the FDA issued a drug safety communication to relay the Advisory Committee's findings. This communication also highlighted a recent FDA safety review which found that serious adverse effects involving tendons, muscles, joints, as well as peripheral neuropathy and central nervous system adverse effects could occur within the same patient. In the cases of multiple adverse effects occurring in the same patient that had been reported to the FDA, symptoms occurred within hours to weeks after starting treatment and lasted for an average of 14 months, with the longest duration being 9 years.

On July 26, 2016, a subsequent drug safety communication updated prescribers that the new labeling changes had been implemented.[17] The following November, the American Academy of Pediatrics published a Clinical Report on the use of systemic and topical fluoroquinolones to call attention to the FDA recommendations.[17] The authors, writing for the Committee on Infectious Diseases, noted that while injury to developing bones or joints has not turned out to be a significant risk, the safety reviews conducted by the FDA suggest an increased risk for musculoskeletal adverse events.

The most recent FDA drug safety communication on fluoroquinolones was issued on July 10, 2018 to notify healthcare providers of its intention to strengthen current warnings in the prescribing information of all fluoroquinolones regarding the risk for clinically significant hypoglycemia and mental health adverse effects.[3] While the labeling of most of the fluoroquinolones already contained a warning that blood sugar disturbances, including high blood sugar and low blood sugar, could occur with their use, this new communication highlighted the potential severity of these reactions, including a specific description of the risk for hypoglycemic coma.

The section on mental health adverse effects was made more prominent by separating it from the warnings on central nervous system adverse effects and the language was made consistent across the therapeutic class. The specific mental health adverse effects added to or updated included:

  • disturbances in attention

  • disorientation

  • agitation

  • nervousness

  • memory impairment

  • delirium