FDA requires safety labeling changes for fluoroquinolones to strengthen warnings on adverse reactions

Jul 11 2018

The U.S. Food and Drug Administration today is requiring safety labeling changes for a class of antibiotics called fluoroquinolones to strengthen the warnings about the risks of mental health side effects and serious blood sugar disturbances, and make these warnings more consistent across the labeling for all fluoroquinolones taken by mouth or given by injection.

"The use of fluoroquinolones has a place in the treatment of serious bacterial infections -; such as certain types of bacterial pneumonia -; where the benefits of these drugs outweigh the risks, and they should remain available as a therapeutic option. The FDA remains committed to keeping the risk information about these products current and comprehensive to ensure that health care providers and patients consider the risks and benefits of fluoroquinolones and make an informed decision about their use," said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research.

FDA-approved fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, moxifloxacin (Avelox), ofloxacin, gemifloxacin (Factive) and delafloxacin (Baxdela). There are more than 60 generic versions. The safety labeling changes the FDA is requiring today were based on a comprehensive review of the FDA's adverse event reports and case reports published in medical literature.

Across the fluoroquinolone antibiotic class, a range of mental health side effects are already described in the Warnings and Precautions section of the drug labeling, but differed by individual drug. The new class-wide labeling changes will require that the mental health side effects be listed separately from other central nervous system side effects and be consistent across the labeling of the fluoroquinolone class. The mental health side effects to be included in the labeling across all the fluoroquinolones are disturbances in attention, disorientation, agitation, nervousness, memory impairment and delirium.

Additionally, the recent FDA review found instances of hypoglycemic coma where users of fluoroquinolones experienced hypoglycemia. As a result, the Blood Glucose Disturbances subsection of the labeling for all systemic fluoroquinolones will now be required to explicitly reflect the potential risk of coma with hypoglycemia.

Today, the FDA also published a drug safety communication about safety information regarding hypoglycemic coma and mental health side effects with fluoroquinolones.

The FDA first added a Boxed Warning to fluoroquinolones in July 2008 for the increased risk of tendinitis and tendon rupture. In February 2011, the risk of worsening symptoms for those with myasthenia gravis was added to the Boxed Warning. In August 2013, the agency required updates to the labeling to describe the potential for irreversible peripheral neuropathy (serious nerve damage).

In 2016, the FDA enhanced warnings about the association of fluoroquinolones with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves and the central nervous system. Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections, the FDA determined that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options.

The patient Medication Guide that is required to be given to the patient with each fluoroquinolone prescription describes the safety issues associated with these medicines.