Tag Archives: Dr. Bennett

Fluoroquinolone Toxicity Studies

A couple fluoroquinolone toxicity studies are being conducted.

Dr. Charles Bennett, a Professor at the University of South Carolina College of Pharmacy, is conducting a study of genes related to fluoroquinolone toxicity. Dr. Bennett is seeking “floxed” participants in the study. In the “Floxed Friday” newsletter sent out by Michelle Polacinski – Floxie, Director, and Producer of ‘Floxed’ – the following information about how to participate was shared:

This study is open to those who have experienced FQ Toxicity. If you are interested in participating, please send your contact information (name, address, phone #) to abc8@email.sc.edu and please write “FQ Study” in the subject line.

You will receive instructions, a consent form, and a survey to complete. A saliva test kit will then be mailed to you. You will provide your saliva sample, as instructed. Then, you will mail the sample back to the university, as instructed.

This is very exciting! This study has the potential to answer questions about who is predisposed toward fluoroquinolone toxicity, and, as genetic testing gets easier and easier, perhaps it will someday lead to screening tools that will keep doctors from prescribing fluoroquinolones to people who are genetically predisposed toward fluoroquinolone toxicity.

I encourage you all to participate in the study. (FYI – just my personal experience – I emailed my information to the email address provided twice, but have not yet heard back from anyone, so I don’t have any personal experience of this study. I just have heard about it and I’m passing on the information I heard.)

Another study of fluoroquinolones is being conducted by the Mayo Clinic (the branch in Rochester, Minnesota). It is a clinical trial entitled, “A Study to Evaluate Biomarkers of Fluoroquinolone-induced Mitochondrial Toxicity” and more information about it can be found on the Mayo Clinic web page about the study.

Per the clinical trial announcement:

“The purposes of this study are to determine if patients treated with fluoroquinolone (FQ) antibiotics have depletion of mitochondrial DNA (mtDNA) in buccal swab samples, and whether the degree of depletion correlates with the likelihood of developing FQ-associated toxicity.”

This is a very exciting study for the floxed community in a couple ways. First, it is to determine whether or not mtDNA is depleted in humans. Several studies have shown that fluoroquinolones deplete mtDNA in cells studied in labs, but I don’t believe that any studies have shown the depletion of mtDNA in people.

The study requires recent administration of a fluoroquinolone antibiotic (the inclusion criteria includes, “Treatment with oral and/or intravenous FQ antibiotics (ciprofloxacin, levofloxacin, moxifloxacin, delafloxacin) that has been initiated upon, or within 24 hours of, admission to the HIM service or at time of initial Infectious Diseases consultation and lasting > 48 hours.“) so I don’t recommend that any floxed people sign up for it. Some people have expressed dismay over fluoroquinolones being studied by being given to people, and, while I understand the misgivings, fluoroquinolones are given to people all the time and I feel encouraged that there are people who are studying the effects of fluoroquinolones, even if the study requires administering them. I am assuming that the people who are a part of the study will be in-need of antibiotics and that fluoroquinolones would be given to them regardless of whether or not they participate in the study – I at least hope so, because giving these drugs to people who don’t have an infection or other need for them is unethical.

I appreciate the acknowledgement that is implicit in both these studies. In studying both genetic markers and mtDNA depletion as they relate to fluoroquinolone toxicity, fluoroquinolone toxicity is being acknowledged by the scientists and doctors conducting the studies. Acknowledgement is helpful in that it leads to studies which lead to more information which lead to fewer people getting hurt by fluoroquinolones and/or maybe even a cure for fluoroquinolone toxicity. We can at least hope for those things.

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Dr. Bennett identifies what the government should be doing — but isn’t — to guard against unsafe prescription drugs

Dr. Charles Bennett has been an advocate for addressing fluoroquinolone safety concerns for many years. He has has filed multiple petitions with the FDA to get them to change the warning labels for fluoroquinolones–one of the petitions is to get the FDA to add Psychiatric Adverse Events to the Levaquin/levofloxacin warning label, another is to have the FDA add “Possible Mitochondrial Toxicity” to the Levaquin Label, another requesting a black box warning to specifically identify psychiatric adverse events, including suicide and suicide-related adverse events, and likely others. These petitions have led to warning label changes, and have been featured in many of the news stories about fluoroquinolones. Dr. Bennett has also testified before the FDA about fluoroquinolone adverse reactions, and has helped many “floxies” to gain information and support. He is a wonderful advocate, and his advocacy work has increased the credibility of other advocates for fluoroquinolone toxicity awareness. He has changed how many people think of fluoroquinolones, and he has changed how fluoroquinolones are prescribed. He is making a difference.

Dr. Bennett recently wrote a wonderful editorial that was published in the LA Times entitled, “What the government should be doing — but isn’t — to guard against unsafe prescription drugs.” I highly recommend that you read and share it. He has some great ideas and insights, some of which I’m going to highlight in this post (all italicized and indented sections of this post are quotes from the editorial).

He, and his co-authors, state:

The failings are at every point in the system, starting with drug approvals. But we believe there is a particularly serious problem with the mechanisms for identifying, monitoring and disseminating information about issues with a drug after its release.

Once a drug is approved for market, the FDA relies on an informal and ineffective system of case reports and citizens’ petitions to alert it to problems and adverse events. In the past, case reports, submitted to medical journals by physicians, served as an important mechanism for detailing drug toxicity. But today, because of changes to editorial guidelines, peer-reviewed journals rarely accept such reports for publication.

Indeed. Take it from a doctor who specializes in studying adverse drug reactions that the current system of tracking and addressing concerns about adverse drug reactions is failing and ineffective. How many of the thousands (perhaps millions) of adverse reactions to fluoroquinolones have been reported to the FDA through either the adverse event reporting system, a case report, or a citizen’s petition? Unfortunately, not many. It should be noted that, “Many studies have documented that only 10%-15% of serious adverse reactions are reported” to the FDA. Though I encourage every “floxie” to report his or her adverse reaction to the FDA, a voluntary reporting system that is confusing and difficult to navigate, is not a particularly effective way of tracking the actual incidence of adverse drug reactions.

Dr. Bennett also notes that Citizen’s Petitions (many of which he has filed) are not an effective tool for tracking and evaluating post-market adverse drug reactions:

Citizens’ petitions, in which any citizen can petition the FDA to report adverse drug effects, are intended to be another check. But the petition process is cumbersome, and they are rarely granted. Of the 1,915 Citizens Petitions filed in the 12-year period between 2001 and 2013, a total of 13 were granted. Many go unanswered altogether.

The citizen’s petitions filed by Dr. Bennett, Public Citizen, and others, have been helpful advocacy tools, but, as Dr. Bennett and his co-authors point out, they have not been adequate.

Rather than continuing with the ineffective system of depending on patient and doctor reports of adverse reactions, citizen’s petitions, and case-reports to monitor and track adverse drug reactions, Dr. Bennett suggests that a new system for tracking and monitoring drugs with black-box warnings be implemented.

We propose a “black box” database or “registry,” publicly available and simple to use, that would contain extensive information about where, by whom and for what purpose black box drugs are prescribed, as well as where and in what quantities such drugs are being distributed and sold. Information about adverse side effects, culled from the myriad of government databases that now collect them, would also be consolidated in an open form and format.

In addition to the benefits of a black box database/registry noted above, a black box database/registry also has the potential to decrease usage of drugs that have black box warnings:

Is there a chance that the existence of a black box registry would decrease the use of those drugs? Possibly, and that would be a good thing. Too often black box warnings are seen as meaningless, and they are counteracted with marketing campaigns that promote off-label use. If adding more transparency, thought and effort to the prescription and sale of dangerous drugs winds up decreasing their use, that will likely be a beneficial side effect.

It would be WONDERFUL if there were a system in-place that cut down on unnecessary fluoroquinolone prescriptions. It would be WONDERFUL if there were a system in-place that adequately communicated the real risks of fluoroquinolones. I think that Dr. Bennett’s idea of creating a black box registry is an excellent way to do both those things, and it’s absolutely worth a try. The system that we currently have for tracking and addressing adverse drug reactions is woefully inadequate. Change is good – especially if it is in the direction of making people safer.

Thank you Dr. Bennett and co-authors for writing “What the government should be doing — but isn’t — to guard against unsafe prescription drugs.” Your insights and advocacy are greatly appreciated!

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