A Slow Response But At Least A Response

I filed a petition with the FDA in 2014 to ban the Flouriquinolone Class of antibiotics from common prescription use. I requested it to have the label changed so that it is not used for everyday conditions, such as UTI, bronchitis, and similar diseases that are easily treatable by other antibiotics and which do not need a broad spectrum antibiotic.  I recommended to have Fluroquinolones be reserved for life-and-death situations only when there are no alternatives and to change the label reflecting all adverse side effect that were already well understood, and to “blackbox” the medication. In my previous article on this subject, found here, I updated the FDA information, since new side effects made it imperative to immediately restrict all quinolones from common use. Why is this all interesting now? Because of a letter I just received from the FDA!

4-Years in the Making and an Invalid Response

I received a letter today from the FDA, which I have scanned for safekeeping–my address is removed–which I uploaded OriginalFDA Quinolone comment response to 2014 received on 12-24-2018 for your review. The most interesting thing about it is that it is already extinct!

Here is a summary of important notes:

Re: Docket No. FDA-2014-P-1753    DEC 19 2018

Dear Dr. Stanton:

This letter responds to your citizen petition received by the Food and Drug Administration (FDA or the Agency) on October 28, 2014 (Petition). The Petition requests FDA to restrict the administration and use of ciprofloxacin hydrochloride ( ciprofloxacin) to “life or death” medical emergencies treated in emergency rooms, surgical suites, and intensive care units (ICU). The Petition urges FDA to limit the use of ciprofloxacin to only the most serious medical circumstances because the drug has serious adverse effects, and its over-prescription has caused a decline in antibiotic effectiveness in treating life-threatening bacterial infections (Petition at 1, 5). According to the Petition, the adverse events associated with ciprofloxacin, some of which the Petition claims to be permanent and disabling, outweigh the benefits of using the drug to treat simple infections (Petition at 5). The Petition claims that there are safer alternative antibiotic treatments available for most of the indications listed in ciprofloxacin’s labeling and urges FDA to encourage the use of these alternative antibiotics to help preserve the effectiveness of ciprofloxacin (Petition at 2)…

…Since ciprofloxacin was approved, FDA has approved  labeling changes for ciprofloxacin and other systemic fluoroquinolones to include an expansion of the BOXED WARNING, WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS sections to update the description of the muscular, cardiac, neurological, and psychiatric risks associated with the use of these drugs. The Agency approved these changes based on spontaneous reports and reviews of the literature. We discuss some of these regulatory actions below…

…The Agency convened the meeting to discuss the risks and benefits of systemic fluoroquinolone antibacterial drugs for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis in patients with chronic obstructive pulmonary disease, and uncomplicated urinary tract infections in the context of available safety information and the treatment effect of antibacterial drugs in these clinical  conditions. The Committees voted that the benefits and risks of fluoroquinolones did not support  the then-labeled indications for: (1) acute bacterial sinusitis (Yes, O; No, 21; Abstain, 0), (2) acute bacterial exacerbation of chronic bronchitis in patients with chronic obstructive pulmonary disease (Yes, 2; No, 18; Abstain, 1), or (3) uncomplicated urinary tract infections (Yes, 1; No, 20; Abstain, 0).20 FDA considered the Committees’ recommendations and reviewed the available scientific and medical information relating to ciprofloxacin.21 On May 12, 2016, FDA notified systemic fluoroquinolone NDA holders and certain ANDA holders22 that they must modify their products’ labeling to reflect a new limitation of use statement and make clear that using fluoroquinolones for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis in patients with chronic obstructive pulmonary disease, and uncomplicated urinary tract infections should be reserved for patients with no other treatment options. FDA also informed the fluoroquinolone NDA holders and certain ANDA holders that they must modify the labeling (including the BOXED WARNING and patient Medication Guides) to reflect the serious risk of disabling and potentially irreversible adverse reactions that have been observed to occur together, including tendinitis, tendon rupture, peripheral neuropathy, and central nervous system effects and events.23 FDA also released a DSC on the same day advising the public and medical practitioners of the new limitation of use.24 On July 26, 2016 FDA approved these labeling changes and issued a second DSC informing the public and medical practitioners of the new warning information contained in the labeling. 2…

…Finally, after receiving adverse event reports from FD A’s Adverse Event Reporting System (F AERS) and conducting follow-up scientific and medical research (including reviewing published literature), FDA determined that systemic fluoroquinolone antibacterial drugs needed additional labeling changes. On July 10, 2018, the Agency notified NDA holders and certain ANDA holders of systemic fluoroquinolones that they must modify their products’ labeling to expand on possible serious low blood sugar levels and mental health side effects associated with systemic fluoroquinolone use.26 On October 18, 2018, FDA approved these labeling changes.27

B.The Benefits of Ciprofloxacin Outweigh the Risks for its Currently Labeled Indications

As discussed above and highlighted in the current fluoroquinolone class labeling, FDA recognizes that there are certain potential serious adverse events associated with
fluoroquinolones and agrees that fluoroquinolones should not be used as a first-line treatment for certain bacterial infections. However, the Agency disagrees that the use of ciprofloxacin should be limited only to “life or death” circumstances and administered in the ICU, emergency room, and surgical suites…

…Therefore, in certain circumstances, ciprofloxacin has advantages over other antibacterial drugs. In addition, due to its spectrum of activity (i.e., range of bacteria susceptible to the agent), ciprofloxacin is often the only orally available agent a
patient may have as a treatment option as resistance to several oral antibacterial drugs is fairly common. In these situations, the benefits of prescribing ciprofloxacin are substantial, even when the drug is administered outside of emergency room, operating room, and ICU settings…

…prescribing ciprofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 33 A similar risk exists when a medical provider prescribes ciprofloxacin as a first-line drug to treat certain
infections that are more properly treated by a non-fluoroquinolone. However, these risks have been mitigated by updating labeling to reflect current medical and scientific thinking and by communicating to medical professionals about the potential risks associated with prescribing ciprofloxacin for particular indications. The labeling changes made in 2016, which targeted the three specific indications that may have contributed to overuse of fluoroquinolone antibacterial drugs, may help reduce the inappropriate prescription of ciprofloxacin that contributes to the development of resistance…

…FDA has determined that the benefits of allowing the use of ciprofloxacin outside of the emergency room, operating room, and the ICU outweigh the risks of the drug’s potential adverse events. If the Agency becomes aware of a potential new safety concern, it will take regulatory action, as appropriate, to ensure that the benefits of ciprofloxacin continue to outweigh its risks.” (emphasis mine)

The above is the summary of highlighted comments. Why is this so interesting? Because in their last release, they stated the opposite:

The US Food and Drug Administration warned on Thursday that the benefits of fluoroquinolone antibiotics do not outweigh the risks — which include aortic aneurysm — for certain patients, according to the latest research. The research is based on reports of patient problems and on studies published between 2015 and 2018. (See here) (emphasis mine)

Why Doctors May Be Confused

While I am tickled to death that the FDA takes time to actually respond to petitions, I am surprised to get a letter stating that the FDA has determined that the benefits of allowing the use of ciprofloxacin outside the ER and the ICU outweigh the risks, while at the same time this letter was mailed to me, the FDA has already decided that the benefits do not outweigh the risks for certain patients.

I can’t help but wonder if doctors are confused since they continue to prescribe Cipro (ciprofloxacin) and other fluoroquinolones like candy for the smallest of diseases, especially for the ones the labels advises them not to. Could the FDA be more precise? I am sure but won’t hold my breath.

The ultimate job is still on you: protect yourself by educating your doctor! Print out the latest FDA documents when you go visit your doctor for an infection and hand a copy to them so they know that you know that quinolones are not to be prescribed, unless there is no alternative.

Comments are welcome, as always, and are moderated for appropriateness

Angela