NCHR Testimony at FDA on the Benefits and Risks of Systemic Fluoroquinolone Antibacterial Drugs


Comments to the Joint Meeting of the Antimicrobial Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee

Thank you for the opportunity to speak today. My name is Dr. Tracy Rupp: I was previously a clinical pharmacist at Duke University Medical Center and am now a senior fellow at the National Center for Health Research. Our research center analyzes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from pharmaceutical companies and I have no conflicts of interest.

We strongly support efforts to improve antibiotic use and drug safety. While quinolones can be life-saving drugs for certain types of infections, we must re-examine their safety and efficacy in light of new information to ensure the benefits outweigh the harms.

The antibiotics we’re reviewing today were approved for acute bacterial sinusitis (ABS) and acute bacterial exacerbation of chronic bronchitis in patients who have chronic obstructive pulmonary disease (ABECB) based on non-inferiority trials in which​ effectiveness could not be established because they were compared to drugs that were never compared to placebo, or drugs that themselves were not shown to be better than placebo. Subsequent post-market placebo-controlled studies have been conducted in an attempt to answer the effectiveness question and have ​found them to be of little or no benefit for ABS and mild ABECB.

Meanwhile, we’ve learned much more about the potential harms for patients. We know from experience that quinolones are a high-risk class of antibiotics – in fact, five other quinolones have been withdrawn from the market already because of drug-related adverse effects and unclear benefits. Those that remain on the market have added warnings on their labeling about the risk of tendinitis and tendon rupture, cardiac arrhythmias, and peripheral neuropathy. Today, we heard about a new condition called “fluoroquinolone-associated disability.” Most of the affected patients were previously healthy and became severely disabled within hours or days of taking a quinolone.

Despite the introduction of Boxed Warnings for tendinitis and tendon rupture in 2008 and the enhancement of Warnings and Precautions for the potential irreversibility of peripheral neuropathy in 2013, quinolone use has not decreased.

Therefore, we recommend the following:

  1. Since there is no evidence of benefit in the pre- or post-​approval studies for ABS and mild ABECB and clear evidence of harm, we strongly urge that quinolone manufacturers voluntarily withdraw the indications for ABS and mild ABECB. If these indications are not voluntarily removed, we recommend FDA use its authority to remove them.
  2. Since quinolones present a risk of harm that is disproportionate to the benefit for uncomplicated urinary tract infection (uUTI), we recommend revising the label to state that quinolones should be reserved as second line therapy for symptomatic uUTI.
  3. Since current warnings have been ineffective, we recommend FDA implement a risk evaluation and mitigation strategy for the quinolone class of antibiotics. REMS information should include all of the Warnings and Boxed Warnings already on the label as well as those we discussed today, including fluoroquinolone-associated disability.

Thank you for the opportunity to comment today and for consideration of our views.



On July 10, 2018, in an effort to strengthen and make more consistent warnings about the risks of mental health side effects and serious blood sugar disturbances across the entire class of fluoroquinolones, the FDA now requires mental health side effects to be listed separately from other central nervous system side effects and that the Blood Glucose Disturbances subsection of the labeling be required to explicitly reflect the potential of coma with hypoglycemia.

See the FDA Press Release here.