Levaquin Adverse Drug Reactions, More Than Forty Years, Tendon Rupture, Anthrax Scare, Rampant Ignorance

Comment: What is behind the ignorance and denial found within the medical community regarding the true safety profile of the fluoroquinolones?

An editorial in response to the FDA's recent addition of "Black Box Warnings" to the fluoroquinolone class.

Written by the Director of the Fluoroquinolone Toxicity Research Foundation, Mr. David T. Fuller.

The Fluoroquinolone Toxicity Research Foundation continues to collect post-marketing reports regarding the non-abating nature of the severe and crippling adverse drug reactions associated with fluoroquinolone therapy via the Internet. Ever since the research forum went on line, the Fluoroquinolone Toxicity Research Forum hosted by Yahoo has received thousands of reports, including numerous associated fatalities. The homepage for the Fluoroquinolone Toxicity Research Foundation, www.fqresearch.org has accumulated over 4000 medical journal entries, newspaper articles, post marketing reports, lawsuits and other such supporting data the clearly shows the rampant ignorance and denial within the medical community regarding the non-abating nature of such events.

For more than forty years, since the introduction of Nalidixic Acid in 1962, the victims of fluoroquinolone toxicity have been denied the medical care they so desperately need as their physicians have routinely failed to recognize, treat and report such events. Peripheral Neuropathy, spontaneous tendon rupture, severe and non abating joint and tendon damage, resulting from such toxicity, are all known, listed and published adverse drug reactions to these chemotherapeutic agents, commonly referred to as fluoroquinolones or quinolones. Yet the victims continue to be told by their physicians "it cannot be the drug".

Numerous news stories since the anthrax scare back in 2001 have documented such injuries, with the most recent being the death of the daughter of one member of the research forum, whose death was the direct result of such careless scripting of these toxic and dangerous drugs. Another forum, the quinolone adverse drug reaction forum, hosted by Yahoo since February 14, 1999, has accumulated over 57,000 such post regarding the damage this class of chemotherapeutic agents can and will do. The law firm of Sheller, Ludwig and Badey, one of the largest class action and medical malpractice firm in the Northeast, had filed a class action lawsuit against Bayer AG, the manufacturer of Cipro. This suit was filed on behalf of all those who have suffered such damage including the Capitol Hill Staff, the Washington Postal Workers, and the employees of the American Media who were exposed to Ciprofloxacin as a result of the Anthrax Scare. This suit was later withdrawn alleged to be the result of the astronomical cost of such litigation.

In spite of the overwhelming evidence of the non-abating nature of such injuries, the FDA continues to approve new drugs within this class together with new indications for those already on the market. Ignoring the 9,711 reports that include 806 associated deaths and 39,128 total reactions found within the AERS reports for Levofloxacin. (Levaquin Nov. 1997 - May 30, 2007) In 2004 these numbers were 5,276 reports, 473 associated deaths and 19,792 total reactions respectively. Together with the 8,766 reports which include 837 associated deaths and 40,395 total reactions for Ciprofloxacin found within the AERS reports as well. (Nov. 1, 1997 - June 5, 2007) Where as these numbers were 4,995 reports, 480 associated deaths and 20,890 total reactions in 2004. As well as the following:

Floxin: Nov. 1997 - May 30, 2007

Total reactions: 13,495

Total death outcomes by case: 311

Total individual safety reports: 2,962

Proquin (ciprofloxacin) Nov. 1, 1997 - June 5, 2007

Total reactions: 40,151

Total death outcomes by case: 831

Total individual safety reports: 8,688

Tequin: Nov. 1997 - June 5, 2007

Total reactions: 15,494

Total death outcomes by case: 196

Total individual safety reports: 5,307

Factive: Nov. 1997 - June 5, 2007

Total reactions: 1,979

Total death outcomes by case: 7

Total individual safety reports: 1,108

Avelox: Nov. 1997 - June 5, 2007

Total reactions: 30,160

Total death outcomes by case: 337

Total individual safety reports: 7,391

Almost fifty percent of such chemotherapeutic agents have been removed from clinical practice or their use severely curtailed, due to toxicity issues. Yet, Mr. MacCarthy, the 2001 Vice President of U.S. Medical Science at Bayer's West Haven facility stated in 2001"If you are telling me that someone had these effects and they were persisting, long term, months to years after treatment I would be surprised."

The members of the Fluoroquinolone Toxicity Research Foundation had been telling Mr. MacCarthy's employer exactly that for years prior to him making such a statement to the press. Those within the media who have an interest in interviewing those who "had these effects and they were persisting, long term, months to years after treatment" are welcomed to visit our website and forum. For we state unequivocally that Mr. MacCarthy was being less than forthright in the statements he had made back in 2001. Such documentation has been made available to the firm he works for year after year. The adverse reactions experienced by the members have shown to be both persistent and non-abating, "year after year", contrary to what Mr. MacCarthy had stated publicly. As one member of the forum so eloquently stated, "Mr. MacCarthy is mistakened"(sic) as we have the documentation as well as hundreds of such victims to prove all that we state here which is available for public scrutiny.”

Those within the media who have an interest in interviewing those who “had these effects and they were persisting, long term, months to years after treatment” are welcomed to visit this any one of the thousands of such websites found on the Internet as well. Mr. MacCarthy apparently could not be bothered to take the time to do so prior to making the comments that he had in 2001, in my humble opinion.

Here we are SEVEN years later, and we still continue to hear such denials from the manufacturers and the medical community even though these numbers have increased dramatically. Levaquin has been reported as having the most numerous, non-abating and severe adverse drug reactions associated with its use on Mediciations.com

A review of the online adverse drug reaction reporting forum: www.Medications.com (October 2002 – February 2004) revealed that Levaquin was associated with approximately 17% of ALL adverse drug reactions being reported to this site, irregardless of the drug being reported upon. Medications.com started receiving such reports as of October of 2002. Medications.com is an Internet community that allows people interested in commonly prescribed drugs to interact so that they can discuss the implications -- both positive and negative of using these important tools in modern medicine. Medications.com list over 4,500 drugs in common use to date, users have posted thousands of side effects and messages about many of these drugs.

The total number of adverse reactions, regardless of the drug mentioned, as of 2-11-2004, totals approximately 4,469. Levaquin, by far, received more such post than ANY other fluoroquinolone drug listed on this site. Of the 774 adverse reactions reported for all of the fluoroquinolones listed, 752 were for Levaquin. The only fatality listed for a fluoroquinolone was for Levaquin. 97.5% of all adverse reactions to the fluoroquinolones were reported for Levaquin. As such reports are received anonymously the verification of such reports was not feasible nor did we attempt this. But one can assume that receiving this many reports over a sixteen-month period that the majority of such reports are indeed valid. This study also lacks the necessary controls required to present the above as fact and as such should be viewed for debating purposes only.

A review of the side effects posted on Medications.com (October 2002 – February 2004) for the fluoroquinolones used in clinical practice in the United States revealed the following:

Avelox 8 post

Ciprofloxacin 7 post

Floxin 5 post

Levaquin 752 post w/(1) fatality

Tequin 2 post

The predominate adverse reactions reported for Levaquin are as follows:

Nuerotoxicity

Tendon Damage and or rupture

Insomnia

Non abating injury (multiskeletical)

Peripheral Neuropathy

Gastrointestinal

Anxiety and Panic attacks

Vision Problems

Rash, sweats, taste perversions, hearing loss

ALL of which those who suffer such reactions are being told by the treating physician to have no association with fluoroquinolone therapy. This trend is repeated on a number of adverse drug reaction forums dealing with the adverse drug reactions as they relate to the Fluoroquinolones. As the above data has not been verified other than visiting this site and doing a physical count the absolute accuracy has not been determined.

Since the time that this analysis was performed the numbers have increased so dramatically to the point that it is no longer feasible to even attempt such a comparison today. And yet the NUMBER ONE drug with the most adverse reactions, as well as the most severe adverse reactions, continues to be levaquin on that site.

In spite of the overwhelming evidence presented at that 62 Meeting of the Anti-Infective Drugs Advisory Committee that the fluoroquinolones cause irreversible joint damage in the pediatric population the FDA has recently added the use of Ciprofloxacin in the pediatric population, Treating children as young as one years of age. We are currently faced with a clear and present danger regarding these drugs as the FDA, ignoring the tragic results of such careless scripting, has now authorized this use knowing full well that the physician will continue to abuse their discretion.

I challenge the FDA to explain to me how they expect a child who cannot even walk or talk yet to register a complaint of joint and tendon pain. Numerous studies have indicated that such use in a pediatric patient runs the risk of crippling the child for life. One such patient has undergone numerous surgeries to repair this damage and remains crippled to this day. Yet additional clinical trials continue aided and abetted by the FDA, for other drugs in this class other than Ciprofloxacin. A disaster that is detailed within the 62nd meeting of the Anti-Infective Drugs Advisory Committee where it was so eloquently stated:

“…when we talk about the issue of arthropathy that potentially includes a number of things, ranging from simple effusion, for instance, of a knee joint, which might rapidly resolve after the conclusion of therapy, to a more permanent disability. ..” (sic)

“…in September of 1997 there is now a ciprofloxacin suspension which is available, and although it continues to have the same warning statements about arthropathy in juvenile animals and the potential concern in pediatric populations, obviously, the issue of off label use will extend over to pediatric populations in this formulation….”(sic)

“…An important safety question is, what adverse events should be monitored, and Doctor Goldberger alluded to this earlier. This is some of the examples I present. One is permanent lameness, reversible lameness, joint effusion, joint pain, and even latent articular disease or damage that may occur months or years following drug exposure, and there may be others….”(sic)

“…And, data submitted to the Agency, as well as data from the scientific literature, indicate that these lesions don't appear to be reversible…”(sic)

“…Doctor Stahlmann in Berlin is working on an idea that it may be an effect between the endocrines, the magnesium and the matrix and the quinolone. And that data is just coming out now. But as to the exact mechanism, I think you're right. I don't think we have a handle, as far as I know, on the exact mechanism. If there's anybody else that does, I'd sure like to hear it…”(sic)

“… Relating your personal experience, I was wondering about the potential for a delayed effect that in fact one might have a patient who had some histologic changes that would not be manifest clinically for many years. Is that a potential?” (sic)

“… I think it is a potential…”(sic)

“… In trying to assess toxicity with a very sensitive assay, obviously you've got tissue that you can look at in your animal models. There is some human data that were collected by Doctor Urs Schaad using MRI scanning in children and I'm wondering if you can correlate some of your histopathologic findings with MR in the animal model to give us an idea of how sensitive it would be sort of as a follow-up to Doctor Klein's question is the MR something that will be able to predict long-term outcomes, even if there are no clinical symptoms during therapy….”(sic)

“… That I don't know. I'll just be perfectly frank. I don't know. But on the slides I've seen from the animals from the chronic study, the repaired articular cartilage that is there is principally fibrocartilage yet it will provide the same joint margin and it has a calcified base and when we stain it with safrain O screen there's no proteoglycans there so it's going to make it an extremely chondromalaistic area and beyond the one year I can't tell you what the results will be…”(sic)

“…Anyway, it was by a group in Vienna where they looked at the articular cartilage of postmortem specimens of articular cartilage from kids with cystic fibrosis that had been on quinolones for a period of time and they found that there was damage in the chondrocytes….”(sic)

“…There were no deaths reported in U.S. pediatric zero to 18 year old cases where a flouroquinolone was reported as the suspect drug. However, there are eight deaths in the whole cohort of suspect and concomitant flouroquinolone drug reports in the system. Five of these deaths reported ciprofloxacin as a concomitant drug and not the suspect drug. These five were U.S. cases with ages ranging from seven months to six years. The remaining three deaths were all foreign, all 18 year old patients with either ofloxacin or norfloxacin reported as the suspect drug….”(sic)

“…There are 14 reports of arthropathy or arthralgia in the pediatric zero to 18 year old flouroquinolone reports. One report of a 14 year old girl had both ofloxacin and lomefloxacin as the suspect drug so there is an extra count because of the two flouroquinolones on this one report. This particular report indicates that a pediatric orthopedic surgeon diagnosed femoral anteversion as the cause for the girl's arthralgia, therefore you see it listed twice, and not the flouroquinolones. Most of the reports indicated that either an involved knee or elbow with or without other joints was involved….”(sic)

“…One interesting case which is not included on this slide for arthralgias was a 15 year old boy who received ofloxacin IV for an emergency appendectomy and had not grown more than his 70 inches in height over the last year. The 15th percentile for height for a 15 year old boy however is 66.5 inches and the expected growth rate is about two inches per year…”(sic)

“…Three patients had their seizure after the first dose of flouroquinolone, one on ciprofloxacin and the other two on ofloxacin, one of which had received ofloxacin several months earlier…”(sic)

“…The 15 psychiatric reports are a loose grouping of reports which include events ranging from euphoria to psychosis. The ages range from five to 18 years with the median at 15 years. There were two suicide attempts, one on ofloxacin and the other on norfloxacin, three reports of hallucination, one each on ciprofloxacin, ofloxacin and norfloxacin, and one report of aggressive behavior with confusion in a patient who had a psychiatric history and was on norfloxacin. The seven cases of photosensitivity were reported with lomefloxacin with one case on ciprofloxacin and two cases on ofloxacin. …”(sic)

“…I will mention that there were 152 U.S. cases aged zero to 18 years in the U.S. AERS system suspect flouroquinolones in the WHO line listing. The country with the most pediatric reports in the WHO foreign reports is the United Kingdom with 177 reports followed by Germany with 72 and France with 71. The rest of the countries had 20 or fewer reports….”(sic)

“…And with regards to muscular-skeletal events, 21 percent of the patients had an event in ciprofloxacin…”(sic)

“…We have focused our analysis on joint disorders and pefloxacin. 79 cases were reported and consist mainly of arthralgia. I don't know the pronunciation of hydrarthrosis -- 49 persons. It involved the knee in 52 cases, the wrist in 20 cases, the elbow in 20 cases, the shoulder in 6 cases, the ankle in 5 cases, and the hip once. It is associated with a functional discomfort in all cases, and when the duration of this discomfort is known, it can persist more than one month in 61 percent of these cases. But the outcome was favorable in 58 cases without discontinuation in two cases. …”(sic)

“…There have been sequelae in three cases with knee effusions persisting one year later in one case with discomfort following 8 months later in the second case. The third case is articular. It is a 17-year-old patient who experienced arthropathy and the drug was not suspected and the treatment was continued two following months. It leads to destructive arthropathy of the knees and the hip and prothesis was performed three years later. He was treated for a cerebral abscess. The outcome was unknown in 18 cases. In 9 cases, there was no follow-up. In the 9 last cases, we had a follow-up three months later and patients were not -- were still with disabilities and after we have no evolution….” (sic)

“… It is my understanding that one of the children had a joint replacement, is that correct?”

“ Pardon me?”

“ One of the children with the complications had an artificial joint replacement?”

“Yes.”

“…If an irreversible cartilaginous lesion can occur, it is very likely that is going to cause problems down the line and we can't even anticipate what they are like…” (sic)

In spite of the following proven horrendous side effects:

Permanent disability

Permanent lameness

Joint effusion

Joint pain

Latent articular disease or damage that may occur months or years following drug exposure

Lesions that don't appear to be reversible

Potential for a delayed effect that would not be manifest clinically for many years

Damage in the chondrocytes

Eight deaths (five of which involved Ciprofloxacin)

14 reports of arthropathy

Seizures

Stunted growth

Suicide attempts

Hallucinations

Photosensitivity

Knee effusions persisting one year later with destructive arthropathy of the knees and the hip

(And with regards to muscular-skeletal events, 21 percent of the patients had an event in

Ciprofloxacin)

As one member of this advisory committee stated “…If an irreversible cartilaginous lesion can occur, it is very likely that is going to cause problems down the line and we can't even anticipate what they are like…”

As such the FDA has no idea what risk these children face nor how to treat such events once they occur.

Yet in conclusion this committee stated “…We clearly want to encourage development of these drug for use in pediatrics…”.

Within the newest package insert for Ciprofloxacin we find peripheral neuropathy being added as a severe, non-abating adverse drug reaction. A disease state in which the peripheral nerves are so badly damaged the patient will spend the rest of their natural life in severe, non-abating pain for there is no treatment protocol available for such a disease state that offers any relief. But we see no “Black Box Warning” concerning this. Of additional concern is the fact that there are also ongoing clinical trials regarding the use of other chemotherapeutic agents within this class involving pediatric patients as young as six months of age.

For more than forty years since the introduction of Nalidixic Acid in 1962, severe and permanent injury to the patient has been documented. Not one year in the past twenty six has gone by without additional articles being published in the leading medical journals documenting the horrendous damage these drugs can and will do since the introduction of Nalidixic Acic. Now the FDA has given their blessing on the use of chemotherapeutic agents within the pediatric population.

The use of these drugs will NOT be restricted to the approved indications either. The FDA has stated “…obviously, the issue of off label use will extend over to pediatric populations …” So now a child with a minor ear ache or sore throat will risk being crippled for the rest of their lives and the FDA will continue to turn a blind eye to such abuse for it is NOT within the legal rights of the FDA to control how such drugs are used once they have been approved. The FDA has no say in the manner in which a physician chooses to utilized a drug once it has been approved.

As such we now look forward to a whole generation of pediatric patients being destroyed by the careless manner in which such drugs are utilized and the treating physician will continue to fail to recognize, treat and report such events. Just as they have been doing for the past forty six years. Numerous forums now exist on the Internet in which the adult patients have been reporting such severe reactions since 1999. We can all now look forward to the distraught parents of these children joining such forums as a direct result of this total and complete failure of the FDA to protect the health and welfare of the pediatric population. Ignoring their own research and the findings of their advisory committee, they have approved a proven dangerous and toxic drug for the use in children.

The Fluoroquinolone Toxicity Research Foundation continues to collect post-marketing reports regarding the non-abating nature of the severe and crippling (and at times fatal) adverse drug reactions associated with fluoroquinolone therapy via the Internet. Since one of the first such forums went on line back in 1999, over nine years worth of horror stories regarding the damage these drugs can and will do have been forwarded to the FDA. In spite of the overwhelming evidence of such severe and at times fatal adverse reactions, the FDA continues to refuse to take action. In a letter we received from the FDA, (circa 2004) Frances T. Gipson, FACHE Office of Executive Programs Center for Drug Evaluation and Research, stated that “…we will weigh all risks and benefits associated with Fluoroquinolone Class Drugs prior to taking any additional action…We will continue to monitor future adverse events reported to us.” To add insult to injury regarding such inaction by the FDA, Gipson also states “…It was also noted that the majority of those adverse events reported are well-known side effects of the Fluoroquinolone class of drugs…” Three years later (circa 2007) Public Citizen received a reply from the FDA to their petition seeking Black Box Warnings stating the very same thing almost word for word. So did the Attorney General of the State of Illinois in response to their petition filed a year earlier.

For more than forty six years, since the introduction of Nalidixic Acid in 1962, the victims of fluoroquinolone toxicity have been reporting such “well-known side effects”, only to be denied the medical care they so desperately need as their physicians have routinely failed to recognize, treat and report such events. Peripheral Neuropathy, spontaneous tendon rupture, severe and non abating joint and tendon damage, as well as fatalities resulting from such toxicity, are all known, listed and published adverse drug reactions to these chemotherapeutic agents, commonly referred to as fluoroquinolones or quinolones. Yet the victims continue to be told by their physicians “it cannot be the drug” and the FDA continues to “monitor future adverse events.” It surely does not get any sicker than this.

Numerous sites continue to be added to the Internet dealing with these reactions in an effort to draw media attention to those of us who are left outside the city gates, like lepers to be pitied and ignored. On any one of these sites you will find tens of thousands of case histories, posted in the very words of the victims themselves, which describe the horrific suffering they or their loved ones have endured as a direct result of the FDA’s failure to prevent such carnage. You will also find postings regarding those who have forfeited their lives due to the rampant ignorance regarding the adverse reactions associated with these chemotherapeutic agents.

The recent addition of this frivolous “Black Box Warning” only emphasizes the fact that such adverse reactions experienced by such victims have shown to be both persistent and non-abating, “year after year”, contrary to what Mr. MacCarthy had stated publicly seven years ago. The comments made within the video presented by the good doctor from John Hopkins emphasizes the fact that NOTHING has changed since then either when it comes to the rampant ignorance found within the medical community.

Since 1999, over nine years ago, we now have added over fifteen different sites to the Internet that deals with these issues. All dealing with what Mr. MacCarthy claimed to have no knowledge of. Perhaps he may wish to read the postings under “In Fond Memory Of” on the fqvictims site. It has been stated that “dead men tell no tales” but thanks to the efforts of those involved with bringing this new site on line; they have been given a chance to do exactly that. For you will find post after post detailing the horrendous manner in which such fatalities related to the careless and thoughtless use of these dangerous drugs, have occurred. No doubt Mr. MacCarthy has no knowledge of the permanent nature of such reactions either. Over a thousand documented fatalities, forty thousand severe adverse reactions, four thousand medical journal entries, fifteen new adverse reaction websites, nine years worth of post marketing reports, and the FDA continues to state that they intend to “continue to monitor future adverse events reported to us”. The victims continue to report the carnage, yet no one is listening. Perhaps with this “new” warning, somebody, somewhere, will. But somehow I rather doubt that we will find that they work at the FDA.

You would also note that Internet sites that published this new warning and allowed people to post a comment have been overwhelmed with patient’s complaints. I rather doubt that this would be taking place unless the drug in question is truly defective. People have far better things to do with their time I would imagine.

Mr. David T. Fuller

Director

Fluoroquinolone Toxicity Research Foundation

www.fqreseach.org

fqresearch@aol.com

davidtfull@aol.com

About the Fluoroquinolone Toxicity Research Foundation

The foundation is a non profit organization consisting of those who have suffered irreversible and non-abating injury as a direct result of fluoroquinolone therapy. The foundation is dedicated to presenting the research regarding these issues in the hope of preventing such injury to others and to make such research readily available to those who have shown a prior interest. We strive to present accurate and up to date information to the victims of such scripting abuse so that they may be in a position to receive the medical care such rampant ignorance has denied them. Such documentation is readily available via the forum or the homepage www.fqresearch.org

The author of this Editorial has NO financial ties whatsoever with anyone found within the legal or medical field. There are no known conflicts of interest to disclose, and the Foundation has never accepted any donations, of any kind, from any person, corporation, or special interest group since it's inception.