Tag Archives: FDA

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!

*****

FDA Warns About Increased Risk of Aortic Aneurysm and Dissection with Fluoroquinolone Antibiotics

On December 20, 2018, the US FDA released a review that “found that fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the main artery of the body, called the aorta. These tears, called aortic dissections, or ruptures of an aortic aneurysm can lead to dangerous bleeding or even death. They can occur with fluoroquinolones for systemic use given by mouth or through an injection.” (source)

This acknowledgement from the FDA came three years after two major studies showed a statistically significant increase in risk of aortic dissection and aneurysm with fluoroquinolone use. The studies, “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” (JAMA Internal Medicine, 2015), and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” (BMJ Open, 2015) both found that fluoroquinolone use is associated with an increased risk of aortic aneurysm and dissection, with “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” concluding that:

“Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.”

Both “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” are major studies, with “analysis of 1477 case patients and 147 700 matched control cases from Taiwan’s National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011” for the former, and 1.7 million older adults in Ontario, Canada, for the later. They are robust studies that show a statistically significant association between fluoroquinolone-use and aortic aneurysm and dissection.

The FDA took too long to warn the public about the dangers of aortic aneurysm and dissection post exposure to fluoroquinolones, but, better late than never. Here is the full text of the FDA announcement that was published on Thursday December 20, 2018:

[12-20-2018] A U.S. Food and Drug Administration (FDA) review found that fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the main artery of the body, called the aorta.  These tears, called aortic dissections, or ruptures of an aortic aneurysm can lead to dangerous bleeding or even death.  They can occur with fluoroquinolones for systemic use given by mouth or through an injection.

Fluoroquinolones should not be used in patients at increased risk unless there are no other treatment options available.  People at increased risk include those with a history of blockages or aneurysms (abnormal bulges) of the aorta or other blood vessels, high blood pressure, certain genetic disorders that involve blood vessel changes, and the elderly.  We are requiring that a new warning about this risk be added to the prescribing information and patient Medication Guide for all fluoroquinolones.

Fluoroquinolone antibiotics are approved to treat certain bacterial infections and have been used for more than 30 years.  They work by killing or stopping the growth of bacteria that can cause illness.  Without treatment, some infections can spread and lead to serious health problems (see List of Currently Available FDA-Approved Systemic Fluoroquinolones).

Health care professionals should avoid prescribing fluoroquinolone antibiotics to patients who have an aortic aneurysm or are at risk for an aortic aneurysm, such as patients with peripheral atherosclerotic vascular diseases, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients.  Prescribe fluoroquinolones to these patients only when no other treatment options are available.  Advise all patients to seek immediate medical treatment for any symptoms associated with aortic aneurysm.  Stop fluoroquinolone treatment immediately if a patient reports side effects suggestive of aortic aneurysm or dissection.

Patients should seek medical attention immediately by going to an emergency room or calling 911 if you experience sudden, severe, and constant pain in the stomach, chest or back.  Be aware that symptoms of an aortic aneurysm often do not show up until the aneurysm becomes large or bursts, so report any unusual side effects from taking fluoroquinolones to your health care professional immediately.  Before starting an antibiotic prescription, inform your health care professional if you have a history of aneurysms, blockages or hardening of the arteries, high blood pressure, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome.  If you have been prescribed a fluoroquinolone to treat an infection, do not stop the antibiotic without first talking to your health care professional.

We reviewed cases reported to FDA* and four published observational studies1,2,3,4 that showed an increased risk of aortic aneurysm or dissection associated with fluoroquinolone use (see Data Summary).  How some of the studies were designed or carried out, and the ways the data were analyzed could affect the study findings; however, taken together, the results of all four studies provide consistent evidence of an association between fluoroquinolone use and aortic aneurysm or dissection.  The underlying mechanism for this risk cannot be determined from these studies, and the background risk of aortic aneurysm can vary depending on the population.  The background risk has been estimated from nine aortic aneurysm events per 100,000 people per year in the general population to 300 aortic aneurysm events per 100,000 people per year in individuals at highest risk.  Because multiple studies showed higher rates of about twice the risk of aortic aneurysm rupture and dissection in those taking fluoroquinolones, FDA determined the warnings were warranted to alert health care professionals and patients.

We communicated safety information associated with fluoroquinolones in July 2018 (significant decreases in blood sugar and certain mental health side effects), July 2016 (disabling side effects of the tendons, muscles, joints, nerves, and central nervous system), May 2016 (restricting use for certain uncomplicated infections), August 2013 (peripheral neuropathy), and July 2008 (tendinitis and tendon rupture).

To help FDA track safety issues with medicines, we urge patients and health care professionals to report side effects involving fluoroquinolones or other medicines to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

More information about the link between fluoroquinolones and aortic aneurysm and dissection can be found in these studies or articles:

  1. JAMA Internal Medicine, “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone
  2. BMJ Open, “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study
  3. BMJ, “Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study
  4. Baylor College of Medicine, “Ciprofloxacin increases risk of tears, rupture in mouse aortas

Additionally, here are some news articles about the FDA acknowledgement of the link between fluoroquinolones and aortic aneurysm and dissection:

  1. CNN, “Certain antibiotics may cause aortic aneurysm, FDA warns
  2. NBC News, “FDA warns some antibiotics can cause fatal heart damage: Drugs commonly used to treat upper respiratory infection, urinary tract infections should not be prescribed to patients already at risk
  3. Medscape, “More Fluoroquinolone Safety Concerns
  4. WRIC ABC 8 Richmond, “Commonly prescribed antibiotics can cause potentially deadly ruptures, FDA warns

Fluoroquinolone Prescription Guidelines for Children

The ONLY FDA approved uses for fluoroquinolones in children are:

  1. Anthrax
  2. Plague
  3. Complicated urinary tract infections

That’s it.

All other uses of fluoroquinolones in children are off-label. All pediatric fluoroquinolone prescriptions for treatment of sinus infections, uncomplicated urinary tract infections, respiratory infections, diarrhea, ear infections, etc. are off-label. The FDA has not done a cost-benefit analysis, or a safety analysis, for any use of fluroquinolones in children, other than for treatment of anthrax, plague, and complicated urinary tract infections.

The reason that fluoroquinolones are not approved for most pediatric uses is because, “Fluoroquinolone-induced joint/cartilage toxicity has been observed in juvenile animal studies and is species- and dose-specific with canines exhibiting the highest rate of arthralgias. These early observations led to the contraindication of fluoroquinolones in the pediatric population” (source). Additionally, serious musculoskeletal and nervous system adverse reactions occur at higher rates in children treated with fluoroquinolones than children treated with other antibiotics (source). To put it into simple terms, fluoroquinolones have been shown to cause lameness, stunted growth, joint pain, and other permanent musculoskeletal problems in experiments on juvenile mammals (beagle puppies).

Despite the evidence that fluoroquinolones can cause irreparable musculoskeletal damage to juvenile mammals, there are some people who argue that fluoroquinolone use should be expanded in the pediatric population. Additionally, fluoroquinolones ARE prescribed to children, despite the fact that they cause lameness and arthralgia in animals, and the fact that there are no FDA approved indications for fluoroquinolones other than anthrax, plague, and complicated urinary tract infections.

The Hippocratic Oath and the precautionary principle should be the guiding thought processes when prescribing drugs to children. Drugs that have been shown to cause lameness in juvenile animals, and that have multiple black-box warnings on them, should not be given to children. The current black-box warning for fluoroquinolones states that they can cause “disabling and potentially irreversible serious adverse reactions.” No child should be subjected to even the risk of permanent musculoskeletal problems that could result in disability.

Yet… children are being prescribed fluoroquinolones every day, and they are being put at risk. Because of hubris and the general acceptance of off-label prescribing in medicine, many doctors are subjecting children to the risk of fluoroquinolone toxicity–a constellation of symptoms that includes not only serious musculoskeletal problems, but also autonomic nervous system dysfunction, neuropathy, psychiatric disturbances, blood-sugar irregularities, and more.

It’s not okay. Even the FDA, as ineffective as they are, recognizes that it is not appropriate to subject children to the risk of serious and permanent adverse drug reactions unless they are faced with life-threatening infections like anthrax and plague.

But too many doctors either don’t realize that fluoroquinolone adverse-reactions are severe, or they think that they can gauge the appropriateness of the risk of their prescribing behavior better than the FDA, and they prescribe fluoroquinolones off-label. This is absurd, foolish, and dangerous. Off-label prescribing is essentially experimental. It is not “evidence based medicine,” it is “throw it at the wall and see if it sticks” medicine. And everyone whose child was given a fluoroquinolone for treatment of an infection that wasn’t anthrax, the plague, or a complicated urinary tract infection was, in a sense, experimented on. The approved uses for Levaquin/levofloxacin, Cipro/ciprofloxacin, Avelox/moxifloxacin, and the other fluoroquinolone antibiotics in children are limited, but few doctors are paying attention to what the approved indications for fluoroquinolones are, and I doubt that most physicians even know that fluoroquinolones are not approved for use in children for, say, skin infections, or travelers’ diarrhea, or sinus infections, or swimmer’s ear, etc.

It is awful when anyone is prescribed a dangerous drug in a reckless or uncalled-for way, but it’s particularly horrible when it happens to children. Tragically, children are being hurt by negligent, off-label fluoroquinolone prescriptions. It’s not okay. Yet the FDA, and other world-wide regulators of medicines, are not doing anything to stop this practice. If the FDA is going to pretend to regulate the use of pharmaceutical drugs, they should start with curbing the practice of off-label prescribing – especially for pediatric patients. After all, what good are prescribing guidelines if no one pays attention to them?

Fluoroquinolones are too dangerous for anyone who is not facing a life-threatening infection to use. They are certainly too dangerous for use in children. The FDA knows this, yet they are unwilling to do anything to enforce their own guidelines around pediatric fluoroquinolone prescriptions. Tragically, children are being hurt because of doctors who prescribe fluoroquinolones off-label – and the FDA is unwilling to do anything to stop it.

 

Change Will Come

Ruth wrote this guest post. You can read Ruth’s story of fluoroquinolone toxicity in “Ruth’s Story – Cipro Toxicity.” You can also listen to Ruth’s story through her episode of The Floxie Hope Podcast. THANK YOU, for sharing your insight and wisdom, Ruth! 

There was a long period of time after I got floxed that I despaired of anything ever changing in the medical field. I didn’t think doctors would ever change their prescribing habits regarding fluoroquinolones and people would continue to be harmed as I was, until the end of time, basically. But I recently had an epiphany that brought the realization that not only will the overuse of fluoroquinolones stop, it is inevitable that it does stop.

It is true that America’s FDA is doing a poor job of keeping the public safe from bad drugs and faulty medical devices. But I believe that even if the FDA does not become the watchdog it should be, the needed changes regarding fluoroquinolones will come. Probably not as soon as any of us would like, but they will come.

Every summer I work as a pyro technician for a display fireworks company. I have to undergo training for this. I am kept abreast of the requirements of the ATF, our own industry, and our company. Our own company is stricter than the legal requirements as regards safe distances for spectators. Our own industry has made recommendations to improve safety which are also stricter than what the ATF requires. Sometimes these requirements can seem burdensome or inconvenient.

Why would a fireworks company and professional organizations made up of pyro technicians create their own stricter regulations, when it would be easier to just stick with whatever is legally required? Because sane and rational people want to keep the public safe. Yes, we want to put on a good show, make some money and no one in this world actually wants to have to work harder– but at the end of the day no sane and rational person would want to be responsible for injuring another human being.

I believe the doctors themselves and others working in the medical industry will in the end solve this problem, whether or not the FDA ever wakes up and provides some regulations for use of fluoroquinolones that have some teeth. I believe even the drug companies will reluctantly come around due to social pressure or fear of litigation. I believe this because if it happened in one industry it can happen in another.

New and stricter regulations regarding the transport, handling and use of display fireworks have been met with resistance. I don’t want to paint a picture that says every time a new rule is added everybody is happy about it and immediately gets on board with it. But I have heard the arguments for continuing the old ways and I know why they aren’t holding up, why changes are happening despite opposition. The arguments against changing how fireworks shows are done are the same ones that are used against changing how fluoroquinolones are prescribed. They are all flimsy arguments. Here’s my list:

  1. We’ve always done it this way.
  2. It’s easier to do it this way.
  3. It’s cheaper to do it this way.
  4. I don’t believe this really makes a difference for safety, because I personally have never seen anyone get hurt doing it this way.

Let’s take these one at a time:

We’ve always done it this way” simply does not hold up when the science says what you have been doing is not safe. In both industries those advocating for safety have science on their side. Also, it is mainly the older pyros and older doctors using this argument. As they retire, and young people coming in are trained in a different way, this argument will simply disappear. I have had young pyro technicians come to me and say that an older person on the crew showed them how to do something that was inconsistent with training they received. I confirm that they have to do it the way they were trained and I never get an argument from them.

The more experienced person may continue to argue on the basis of, “I have always done it this way,” but the younger person will distrust anything that goes against the training he or she received. I have heard of some medical schools today teaching about fluoroquinolone toxicity syndrome and cautioning students to avoid using FQ’s unless really necessary. These are second and third hand accounts, but if they are true this is a huge win for us.

Some of the older pyro technicians, sad to say, take themselves out of the picture by choosing to continue doing things that we know today are not safe. Doctors who simply refuse to believe in the dangers of fluoroquinolones and take those drugs themselves also may learn the hard way. I’m not saying people getting hurt should be celebrated, absolutely not, but every time the lesson is learned the hard way it is still learned.

It’s easier to do it this way,” does not fly either in the face of how much people can be harmed. In one case we are talking about explosives that, if they don’t go off in the sky where they are supposed to become actual bombs on the ground, and in the other case we are talking about medications whose side effects have been described many times as being like a bomb going off in the person’s body. The amount of voices speaking out on the horrors of fluoroquinolone toxicity helps our case because after people have read our stories they don’t want to risk FQ toxicity no matter how much the doctor may claim Cipro has a great record of safety and efficacy.

The informed patient is going to request that the doctor culture the infection and prescribe accordingly, rather than just prescribe the broad spectrum antibiotic because it is easier. Patients are refusing to take the atomic bomb of antibiotics when they might not need an antibiotic at all. Being handed Cipro and sent on your way without even knowing for sure you have an infection is not going to continue to be accepted medical care. Those of us who speak out to our friends and post about this here at floxiehope and on social media are part of that change, and we can feel good about that. The dangers are becoming known.

Customers can and do drive changes that improve safety. For a recent fireworks show we were informed that the sponsor had requested we follow recommendations by our own industry for distance between loaded mortars. They were actually asking that we follow California’s standards, even though the show was shot in Wisconsin. What reason could we give for not doing what the customer asked? It’s easier to be able to load all the mortars right next to each other in the old style racks than to skip tubes or use the newer ones that have the required spacing? That would have been our only reason to refuse that request: It’s easier to do it the old way.

But the sponsor was making the request because he wanted as safe a show as possible. When patients make requests of their doctors because they want to be as safe as possible the doctor cannot really make any argument that is going to hold up as to why he should not honor those requests. Today we are seeing customers of display fireworks companies taking the time to inform themselves about our industry and what we do! How much more so are patients today taking the time to become informed? In both cases it is happening because the Internet makes information about any subject easily available. When we speak out about our reactions to fluoroquinolones we are helping provide valuable information for others.

It’s cheaper to do it this way,” may seem to be a logical reason to resist changes. After all, companies need to watch their bottom line. But when it comes to a question of money or public safety, the need for public safety will eventually win. There may be a period of time during which companies can make some money while risking the health and safety of other human beings, but eventually that time will end.

People have a desire for self preservation. Whether it is pyro technicians experiencing danger from low breaks, round trippers and finale racks blowing up or patients experiencing or reading about bad ADR’s to a drug, people are going to run the other way when their life or health could be put in danger. Fireworks companies that buy cheap but unreliable product lose workers and have difficulty selling more shows without crews to put them up. Hospitals that use fluoroquinolones for every little thing lose informed patients. If I needed surgery I know where I would go for it, because I know of hospitals (a couple) that do not use fluoroquinolones. If I had to pay out of my own pocket I would do it, because my health and safety is that important to me.

I know of display fireworks companies that are now out of business after consistently focusing on the bottom line instead of safety. I believe the same will hold true for medical facilities, doctors and even drug companies that continue to put money ahead of human health and safety. The display fireworks company I now work for tests all their product and they spend extra money to get product that is going to perform as it is supposed to. They are rewarded for this not only with greater customer satisfaction for some really beautiful shows, but they attract more workers. Pyro technicians would rather work where they feel safe and know they are not putting members of the public at unnecessary risk.

I think the same holds true in health care. I used to work for a medical staffing company in physical therapy. Some companies I temped for definitely cared only about the bottom line, with very high productivity standards. I was so rushed that I knew I was not really able to provide good care, and that put patients and myself at risk. I stopped taking jobs for those companies. Companies that had compassion for both their patients and employees attracted the best workers and could even pick and choose, selecting the cream of the crop of therapists, doctors and nurses. Patient satisfaction went up. While some of the companies that had pushed so hard for productivity were being bought out, the companies that I most preferred to work for were thriving. Decisions made with concern only for the bottom line always come back to bite the companies making them right in the butt.

I don’t believe this really makes a difference for safety, because I personally have never seen anyone get hurt doing it this way,” was the excuse my own doctor used for prescribing Cipro to me for a sinus infection. She had personally never seen anyone have a reaction to Cipro. Well, that is anecdotal evidence and it’s weak. The medical community cannot on one hand say that mountains of anecdotal evidence that fluoroquinolones are harming people is not strong enough evidence and then use anecdotal evidence themselves for their continued widespread use. The changes the FDA recommended for the use of fluoroquinolones in 2016 were made for a reason. A panel of experts heard the testimony of those harmed and looked at medical research regarding fluoroqouinolones and made an informed decision. Making a decision based only on your own experience and observations is not an informed decision.

I say that change will happen in the medical field because in the pyrotechnic industry change is happening. When a change is recommended in how something is done it is probably because somebody got killed doing it the old way. People who want to be safe believe those recommendations even if they personally never witnessed an accident. The same will happen with doctors. Even if they never personally had a patient get floxed, they will follow FDA prescribing guidelines for FQ’s because they do not want to harm other human beings.

One thing that does stand in the way of this change is cognitive dissonance created by the very fact that no sane and rational person wants to harm another human being. As the evidence comes out that fluoroquinolones are insanely dangerous and that the side effects are horrific, long lasting and sometimes permanent, doctors do not want to believe that they put anyone through that. The fact that reactions are delayed means they most certainly could have severely harmed a patient and never known about it because the connection to the antibiotic was never made. It is going to be very hard for doctors to come to terms with this, and I think it is behind a lot of their strident claims that Cipro is “safe and effective.” They need it to be, because if it were not, then there is a good chance they have harmed those they meant to help.

A floxed friend recently shared her experience with an ER doc who tried to give her Cipro for a UTI without even culturing to confirm an infection. She gave him an earful and the expression on his face said that she got through to him. He was horrified. He will either now disbelieve her because he must to avoid a truth he cannot face (that he may have harmed patients) or he will do some research, find the truth, change his prescribing habits and speak to his colleagues. I believe that in time even this cognitive dissonance will be overcome and doctors will do what is right, follow the recommendations of the FDA, and stop prescribing fluoroquinolones in situations that do not warrant their use.

The fluoroquinolone catastrophe has gone on far too long. It can be discouraging to reflect on how many have been needlessly harmed. However, as I have observed changes happening in the pyrotechnic industry that, although sometimes opposed, do happen and do increase public safety, I have to believe that the medical industry is not immune to those same types of changes. I think if it were easier to sue for harm done by pharmaceuticals, that would actually be a good thing, because sadly, there are some people out there who are neither sane nor rational, but consumed with greed. Only one thing gets their attention, and that is losing money. There has to be more accountability for drug companies and doctors who prescribe dangerous drugs needlessly. I do believe it will happen and in the meantime, as we inform people about the dangers of fluoroquinolones we are playing our part in bringing about these much needed changes to the medical industry.

Levaquin Production Stopped by J&J/Janssen Pharmaceuticals

Janssen Pharmaceuticals, part of Johnson & Johnson, has stopped production of (brand-name) Levaquin, according to the article, “Drug maker stopped making popular antibiotic Levaquin amid concerns about mental health side effects” published on the Indianapolis ABC affiliate RTV6 The Indy Channel. Janssen/J&J stopped producing both oral and IV Levaquin in December, 2017. The discontinuation of Levaquin production was confirmed by a Janssen/J&J spokesperson who stated, “The decision to discontinue LEVAQUIN was made due to the wide availability of alternative treatment options, and our focus on developing innovative medicines designed to address unmet medical patient needs.” Though that statement is BS propaganda, it is a direct confirmation from a Janssen Pharmaceuticals spokesperson that JANSSEN/JOHNSON & JOHNSON HAS DISCONTINUED PRODUCTION OF LEVAQUIN.

THIS IS REALLY BIG NEWS! IT’S HUGE! WHOA!

LEVAQUIN HAS BEEN REMOVED FROM THE MARKET!

Unfortunately, there is still plenty of levofloxacin (generic Levaquin, made by hundreds or thousands of generic pharmaceutical producers) on the market, and it is maiming (and killing) thousands of people each year. The fight against these drugs is far from over.

Still, the removal of brand-name LEVAQUIN from the market is a really big deal, and it’s something that we, as a community, should celebrate.

We did this. All the people who filed complaints with the FDA, who testified before the FDA, EMA, and other regulatory agencies, who reached out to the press and told their stories, who shared their story of pain and suffering brought on by fluoroquinolones, all the people who shared articles about fluoroquinolone toxicity, all the scientists who did research showing the harm done by fluoroquinolones, all the advocates, all the people in the floxie community, and all the people who listened–we did this! We screamed loudly enough that people listened. Our efforts made a difference, and Janssen Pharmaceuticals has stopped making Levaquin.

“Never doubt that a small group of committed people can change the world. Indeed it is the only thing that ever has.”—Margaret Mead

I never thought that one of the pharmaceutical giants that has made billions from fluroquinolones would stop making them. Janssen Pharmaceuticals and J&J are huge–they are behemoths–and I never thought that we could move or effect them. But we did.

The efforts of everyone in the “floxie” community contributed to this outcome. We–you–should be proud.

That is my optimistic take on things. We all have an optimistic side. We all have a pessimistic side too, and here’s the bad news.

Janssen decided to stop making Levaquin because, a) their market share was small because generic levofloxacin is cheaper and widely available (“’Levaquin was only about 1 percent of the market share, and 99 percent was the generic,’ said Bennett.”), and b) they were facing significant lawsuits, and to avoid liability for the drugs they created, they pulled them from the market.

Victims of pharmaceuticals can’t sue drug-makers for harming them, they can only sue for “failure to warn” of the dangers of the drugs. This is ridiculous – I can sue you for hitting me in the face with a sledgehammer even if you warn me that you’re going to do it and that it’s going to hurt – but pharmaceutical companies aren’t held to the same standards as you or me. It’s assumed that their deadly products are mainly good and that warning of the potential for bad effects is sufficient to wash their hands of liability and responsibility. On top of that, they don’t even have to directly warn YOU, they only have to say that they warned your doctor, the “learned intermediary” of the dangers of the drugs (or, at least they have to in theory – it’s assumed that doctors actually know what’s on the warning labels for pharmaceuticals… but most don’t). Both the “failure to warn” notion and the “learned intermediary” notions are crap, and I hate them, but they’re how the system is set up.

Because victims of pharmaceuticals can only sue for “failure to warn” the door for them to sue is only open when the drug warning labels change. Fluoroquinolone warning labels have undergone significant changes in recent years. In reverse-chronological order, the following warning label changes have been added to fluoroquinolone labels:

  • In July, 2018, fluoroquinolone warning labels were changed to note that, “Fluoroquinolone Antibiotics: FDA Requires Labeling Changes Due to Low Blood Sugar Levels and Mental Health Side Effects” – Drug Safety Communication
  • In July, 2016, fluoroquinolone warning labels were changed to note that, “FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together” – Drug Safety Communication
  • In May, 2016, fluoroquinolone warning labels were changed to note that, “FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects” – Drug Safety Communication
  • In August, 2013, fluoroquinolone warning labels were changed to note that, “FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection” – Drug Safety Communication
  • In July, 2008, fluoroquinolone warning labels were changed to note that, “FDA is notifying the makers of fluoroquinolone antimicrobial drugs for systemic use of the need to add a boxed warning to the prescribing information about the increased risk of developing tendinitis and tendon rupture in patients taking fluoroquinolones and to develop a Medication Guide for patients.” – Drug Safety Communication

With each of these warning label changes, the door opened for people to sue Janssen and Johnson & Johnson for the harm that Levaquin did to them. (It should be noted that each of these warning labels changed because of advocacy done by the “floxie” community. We screamed, and, slowly, the FDA listened.) Some people did successfully sue the drug companies that hurt them–they gained some compensation and justice.

Perhaps it’s cynical, but it certainly seems more logical than the BS explanation the Janssen spokesperson gave (noted above) that the reason that Janssen Pharmaceuticals took Levaquin off the market was because they didn’t want to be held liable for the blood sugar level changes and the mental health side-effects of Levaquin. They weren’t making much money off it anyhow (because of generics taking the bulk of the market share), this warning label update opened up a new load of liability, and they did a cost-benefit analysis that led them to take it off the market.

All’s well that ends well, and they took Levaquin off the market, and that’s a good thing, right? Well, it’s more complicated than that.

Because of a stupid and asinine rule put in place by the FDA and a lousy decision of the Supreme Court, victims of generic pharmaceuticals cannot sue generic pharmaceutical manufacturers. It all goes back to the “failure to warn” rules noted above. The FDA says that only brand-name drug manufacturers can change drug warning labels, and since generic drug manufacturers can’t change the warning labels, they cannot be held responsible for what’s on the warning labels. This results in victims of generic drugs being unable to hold anyone responsible for the harm done to them by the drugs. There have been a couple cases where brand-name drug companies were held responsible for the harm done by generic drugs, but the precedent wasn’t set very solidly, and most attorneys in most states still aren’t taking cases of people who have been hurt by generic pharmaceuticals. Still, I think that Janssen and J&J saw the writing on the wall–that they could potentially be held responsible for all the Levaquin and levofloxacin-induced mental health side effects, permanently disabling side effects, permanent peripheral neuropathy, tendon tears, and more. So, they hedged their bets. Their legal team, I’m betting, will now argue that they can’t be held responsible for the harm done by levofloxacin because they don’t even make Levaquin any more, and how can they be held responsible for a product that they don’t even produce? My reply is that they can, and should, be held responsible for the drug that THEY CREATED. Johnson & Johnson created and held the patent on Levaquin for a long time. They made billions of dollars off of it. They can, and should, be held responsible for the effects of their creation. The generic drug companies should also be held responsible for the harm that their drugs do, and the FDA should be held responsible for their warning labels (and failure to warn the public about these incredibly dangerous drugs).

We pushed the FDA to change their warning labels. They did, and we should be proud of that. The warning label changes scared Janssen and J&J enough that they stopped production of Levaquin, and we should be proud of that too.

We should also be diligent about the consequences of the removal of Levaquin from the market, and we should continue to work for change in the legal/justice system so that it leans more toward justice for victims, and less toward corporate protection. It is horridly difficult for victims of pharmaceuticals to gain justice or compensation through the legal system as it is currently set up. Janssen pharmaceuticals just made a move to make it even more difficult for victims of Levaquin and levofloxacin to gain justice.

Know what they’re doing. Stay on top of them. Celebrate our victories, then come back to the battlefield fighting. As long as millions of prescriptions of levofloxacin are distributed each year, and thousands of people are maimed by the drugs, our fight isn’t over.

Fluoroquinolone Warning Labels Updated to Include Low Blood Sugar Levels and Mental Health Side Effects

On 7/10/18 the FDA announced that fluoroquinolone (Ciprofloxacin, Levofloxacin, Moxifloxacin, Ofloxacin, and a few others) warning labels are to be updated to include adverse effects on blood-sugar levels, as well as serious mental health effects:

Fluoroquinolone Antibiotics: FDA Requires Labeling Changes Due to Low Blood Sugar Levels and Mental Health Side Effects

This is a HUGE development! To have the FDA acknowledge that fluoroquinolones cause both hypoglycemia (low blood sugar), and that the effects of hypoglycemia include:

  • confusion
  • pounding heart or very fast pulse
  • dizziness
  • pale skin
  • feeling shaky
  • sweating
  • unusual hunger
  • trembling
  • headaches
  • weakness
  • irritability, and
  • unusual anxiety

is a massive move in the right direction for patients and advocates alike.

Additionally, in the same announcement, the FDA noted that the following mental adverse effects can occur with fluoroquinolone use:

  • disturbances in attention
  • disorientation
  • agitation
  • nervousness
  • memory impairment
  • serious disturbances in mental abilities called delirium.

Fluoroquinolone toxicity victims have long known that fluoroquinolones cause both blood sugar disturbances and serious mental health adverse-effects.

Information about the effects of fluoroquinolones on blood-sugar can be found in these posts/articles:

Information about the mental health adverse-effects of fluoroquinolones can be found in these posts/articles:

Additionally, the book, Bitter Pills: Inside the Hazardous World of Legal Drugs by Stephen Fried goes over his wife Diane’s severe psychiatric adverse reaction to a fluoroquinolone (Floxin/ofloxacin).

WE know about the blood sugar and psychiatric effects of fluoroquinolones. The FDA does too. Now they have acknowledged that they know about these horrible, life-altering, sometimes life-threatening effects of fluoroquinolones.

This acknowledgement from the FDA is a big step in the direction of getting fluoroquinolone toxicity more widely acknowledged. However, whenever there are updates to the warning labels, there are many people who say, “so what? It’s just a warning label that no one pays attention to. When is the FDA going to really DO SOMETHING to fix this problem – like find a cure for fluoroquinolone toxicity and/or remove FQs from the market?” Those people have plenty of good points, and I went into some depth in addressing them in the post, “Change the Warning Labels: Why it Matters.” In that post, I assert that one of the things that changes to warning labels does is open the door for people to sue the drug-makers:

“Warning labels themselves may be useless, but during the time when a warning label has things added to it, they can be a great tool, and a big gun we can use against the pharmaceutical companies. The ONLY times lawyers are willing to take cases to sue the drug companies are when warning labels change. For example, when the fluoroquinolone warning labels were adjusted in August, 2013 to note that permanent peripheral neuropathy is a possible effect of fluoroquinolones, several law firms took cases of those who are suffering from peripheral neuropathy after taking fluoroquinolones. Before the warning label changed, they wouldn’t take the cases, because, appallingly, you can’t sue drug companies for hurting you, you can only sue them for “failure to warn” of the harm they’ll do. It’s a really stupid situation and stupid system. BUT, the time when warning labels change is the brief period of time in which you can sue the drug companies for “failure to warn” and it’s the brief period of time when we have the chance to fight the pharmaceutical companies.”

Everyone who has suffered from hypoglycemia or mental health issues post-fluoroquinolone exposure now has a window open to file a lawsuit against the pharmaceutical companies that made the drugs that hurt them. Here are some law firms that have taken fluoroquinolone-harm cases in the past:

There are others too (feel free to let me know if you know of firms that are taking these cases). I hope that Bayer, Johnson & Johnson/Jansen Pharmaceuticals, and all the generic producers of fluoroquinolones pay for the harm that their products are doing to people, and I encourage all victims to seek justice through the legal system.

I hope that this warning label change will help fluoroquinolone toxicity victims to gain acknowledgement and justice. Everyone who has been hurt by these drugs deserves both.

 

 

Fluoroquinolones Increase Risk of Aortic Aneurysm

Evidence is mounting that fluoroquinolone antibiotics (Cipro, Levaquin, Avelox, Floxin, and their generic equivalents) increase the risk of aortic aneurysm and dissection, yet the FDA is denying the connection between fluoroquinolone use and the potentially deadly vascular conditions.

In a May, 2017 notice on fda.gov, the FDA stated:

“As part of our ongoing review of fluoroquinolone antibiotics, FDA is informing the public that patient cases identified by the FDA and findings from published studies currently do not support reports that these medicines may result in detachment of the retina in the eyes, or bulges or tears in the aorta blood vessel called aortic aneurysm and aortic dissection. We will continue to assess safety issues with fluoroquinolones and will update the public if additional actions are needed.”

This statement was made after two major studies were released, showing the statistically significant increase in risk of aortic dissection and aneurysm with fluoroquinolone use. “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” (JAMA Internal Medicine, 2015), and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” (BMJ Open, 2015) both found that fluoroquinolone use is associated with an increased risk of aortic aneurysm and dissection, with “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” concluding that:

“Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.”

Both “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” are major studies, with “analysis of 1477 case patients and 147 700 matched control cases from Taiwan’s National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011” for the former, and 1.7 million older adults in Ontario, Canada, for the later. They are robust studies that show a statistically significant association between fluoroquinolone-use and aortic aneurysm and dissection.

Still, the FDA doesn’t acknowledge that there is a connection between fluoroquinolone-use and these potentially deadly disorders.

Before you defend the FDA by saying something like, “correlation doesn’t mean causation,” or, “an association doesn’t prove anything,” think about what it would take to do a study that would actually show a causal link between fluoroquinolones and aortic dissection and aneurysm–researchers would have to intentionally expose a group of people who they knew were at-risk for aortic dissection and/or aneurysm to Cipro, and another group of people who presumably had an infection to a placebo, then see whether or not they were hurt or died from the exposure. You can’t do this experiment on humans for fairly obvious reasons.

However, you can do the experiment with mice, and a team of researchers from Baylor College of Medicine, the Texas Heart Institute, and Baylor College of Medicine’s Cardiovascular Research Institute, “found that ciprofloxacin, a widely prescribed antibiotic, increases the risk of tears and rupture on the main artery of the body, the aorta, in a mouse model of human aortic aneurysms and dissections (AAD), a disease that carries high risk of death from aortic rupture.” (source) The study showed that:

“normal, unstressed mice treated with ciprofloxacin did not show significant negative effects on the aorta. In mice with moderately stressed aortas that had received the placebo, 45 percent developed AAD, 24 percent developed aortic dissection and none had rupture. On the other hand, 79 percent of the mice with moderately stressed aortas that received antibiotic developed AAD, 67 percent had aortic dissection, and 15 percent had fatal rupture. These results were similar in males and females.” (source)

Though mice with normal aortas weren’t negatively affected by the Cipro exposure, those with stressed aortas were harmed–some fatally. These results, combined with the human population-based longitudinal cohort studies noted above, show, as strongly as we can without subjecting humans to unethical experiments, that fluoroquinoloes (or at least Cipro), increase the risk of aortic aneurysm and dissection in those with previously stressed aortas.

To further their case that fluoroquinolone-use led to aortic aneurysm and dissection, the Baylor researchers also explored the mechanism(s) through which Cipro/ciprofloxacin damages the extracellular matrix, and contributes to the weakening of aortic tissues:

“The researchers then looked deeper into the effects of ciprofloxacin on mouse aortas searching for insights into the antibiotic’s mechanism of action. Compared with the aortas from stressed mice treated with the placebo, the aortic tissue of stressed mice treated with the antibiotic showed more destruction and fragmentation of elastic fibers; decreased activity of LOX, a key enzyme involved in stabilizing the extracellular matrix; increased activity of MMP enzymes involved in extracellular matrix degradation; and enhanced activation of cellular pathways that lead to cell death. Separate laboratory experiments on human aortic smooth muscle cells revealed that sustained ciprofloxacin exposure reduced the expression of LOX while enhancing the expression of MMP and inducing cell death. In these experimental settings, the antibiotic is disrupting the natural processes that maintain the integrity of the extracellular matrix that is essential for normal aortic function.” (source)

Links to studies that show that fluoroquinolones increase expression of damaging MMP enzymes, as well as oxidative stress, can be found in the posts, “Fluoroquinolones Increase Expression of MMPs” and “Antioxidant Depletion by Fluoroquinolones.

The evidence that fluoroquinolones increase the chance of aortic aneurysm and dissection in succeptible individuals is significant. The large population-based studies are compelling, the mouse study establishes a stronger causal link, and many studies that show the damaging effects of fluoroquinolones on cell, collagen, and extracellular matrix, health, each add weight to the argument that fluoroquinolones are contributing to potentially deadly aortic aneurysm and dissections. Yet, the FDA is still claiming that studies don’t support a connection. I’m not sure what else they need in order to convince them that aortic aneurysm and dissection are, indeed, linked to fluoroquinolones. The evidence seems strong and compelling to me, and I suspect that they are just wrong.

Additionally supporting the link between fluoroquinolones and aortic aneurysm and dissection are personal testimonials of connections and damage done. In comments on the post, “Hurt by a Generic Drug? Victims have no Recourse unless the FDA Changes Rules,” published on hormonesmatter.com, one person noted that:

“I took a generic levaquin, a week or so later I had an aortic dissection. It was descending so it was not fixed by surgery. I now have an aortic aneurysm. The tear is pasted together with blood clots. A CT scan every 6 mos to check the size of the aneurysm. Keep my bp below 120.”

Another responded that:

“Took generic Leviquin 7 weeks later aortic dissection. Tore 2 layers of muscle from over my aortic valve down thru and ended in my thighs. Doctor said I would not survive operation. Tear was so big over the valve had to put in synthetic patch.”

In testimony to the FDA, Sherry Reiver stated:

“Four years ago today, my 93 year old dad died. He FELL at home and was taken to the hospital by a neighbor. By the time my husband and I arrived in Florida, my dad had no idea who we were. They THOUGHT he had pneumonia so they IV’d him with Levaquin. It turned out that he did NOT have pneumonia but he continued to hallucinate for 6 weeks and then died. He was sharp as a tack before Levaquin dripped into his body. He did have an aortic aneurysm for many years which was being watched but it ruptured on November 4th. I would have never connected the AA with FQs until I read this research paper dated October 5th 2015. So here is another RARE side effect that can occur, which it did in my dad’s case. How many others have died from AAs and had taken a FQ drug?”

There is significant evidence that fluoroquinolones contributed to these aortic aneurysms and dissections, as well as those of thousands of other patients. These patients weren’t warned that fluoroquinolones could increase their chances of aortic aneurysm or dissection, and they haven’t had the opportunity to gain retribution or justice, in part because the FDA has failed to acknowledge the connection between fluoroquinolones and aortic aneurysm and dissection.

With the publishing of the Baylor mouse study, I hope that the FDA will acknowledge the connection between fluoroquinolone use and aortic aneurysm and dissection. I also hope that acknowledgement from the FDA will lead to justice for victims, and pain for the pharmaceutical company perpetrators who produce and market these dangerous drugs.

Also, all of the studies that connect fluoroquinolones to aortic aneurysm and dissection are greatly appreciated, and I want to thank all of the researchers and scientists who conducted the studies, as well as those who fund them. Research into adverse drug reactions, and patient safety, are important. All of the researchers and scientists who look into adverse drug reactions, especially fluoroquinolone reactions, are appreciated, and I thank them sincerely.