USFDA orders label changes for fluoroquinolones

The US Food and Drug Administration (FDA) had ordered label changes for fluoroquinolones, a class of antibiotics, to strengthen the warnings as they may increase the risk of mental health adverse events (AEs) and blood sugar disturbances.

The label changes must be consistent across all forms of the antibiotics, oral or injection, according to the agency.

Fluoroquinolones are used to treat serious bacterial infections. However, the recent FDA review found instances of hypoglycemic coma where users of fluoroquinolones experienced hypoglycemia. As a result, FDA has said that blood glucose disturbances subsection of the labelling for all systemic fluoroquinolones will now be required to explicitly reflect the potential risk of coma with hypoglycemia.

The FDA warning has put doctors on alert in India too. “We have seen major fluctuations with these widely used antibiotics in patients. Indeed one of the antibiotic of this class (Gatifloxacin) was banned specifically because of propensity to cause low sugar. Doctors should be aware that even a short course may cause fluctuations in sugar values in a well controlled patient with diabetes,” said Dr Anoop Misra, chairman, Fortis-C-Doc Centre of Excellence for Diabetes, Metabolic diseases and Endocrinology.

The changes being required were based on “a comprehensive review of the FDA’s adverse event reports and case reports published in medical literature,” according to the agency.

The label changes follow a series of warning additions over 10 years for the antibiotics.

“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,” said Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

Currently, a wide range of mental health AEs are already included in the labels but differ by individual therapy. The changes require that the mental health AEs are listed separately from the other central nervous system (CNS) AEs. All in all, the mental health AEs include disturbances in attention, disorientation, agitation, nervousness, memory impairment and delirium.

In July 2008, the FDA first added a boxed warning to fluoroquinolones 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 labelling 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.

Currently, FDA-approved fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, moxifloxacin (Avelox), ofloxacin, gemifloxacin (Factive) and delafloxacin (Baxdela). Overall, more than 60 generics have been approved.