Will There Be An Avelox - Liver Toxicity Warning Letter From Bayer Coming Soon In The U.S., Or Not?

In July 2008 FDA Said Avelox, With Other Antibiotics In Fluoroquinolone Class, Would Add A "Black-Box" Warning For Tendinitis And Tendon Ruptures

(Posted by Tom Lamb at DrugInjuryWatch.com)

On July 8, 2008 the FDA announced that a so-called "black-box" warning would be added to the Avelox (moxifloxacin) package insert, or label, to strengthen existing warnings about the increased risk of developing tendinitis and tendon rupture.  At the same time, the FDA announced similar action for these other antibiotics in the fluoroquinolone class of drugs:

Ciprofloxacin (marketed as Cipro and generic ciprofloxacin)
Ciprofloxacin extended release (marketed as Cipro XR and Proquin XR)
Gemifloxacin (marketed as Factive)
Levofloxacin (marketed as Levaquin)
Norfloxacin (marketed as Noroxin)
Ofloxacin (marketed as Floxin and generic ofloxacin)

While reading through some of the material that the FDA made available online in connection with this July 2008 label change for these fluoroquinolone antimicrobial drugs, I found the following:

Fluoroquinolones, like any drug, have possible side effects associated with their use.  Rarely, some side effects may be serious or even fatal; however, most of the risks are mild.  Some of the most serious side effects include seizures, hallucinations, depression, heart rhythm changes (QTc prolongation and torsade de points), and intestine infection with diarrhea.  Rarely, damage to the liver, kidneys or bone marrow, and changes to blood sugar may occur.  (Emphasis added.)

This last sentence brought to mind the February 2008 "Dear Doctor" letter about Avelox / Avalox that Bayer sent out in Europe, which was reportedly intended to emphasize a 2007 label change Bayer made in Europe about, in part, severe and possibly fatal liver toxicity.

I concluded my February 2008 article about this Avelox letter that Bayer sent to doctors in Europe, only with this remark:

We will watch for any similar Avelox "Dear Doctor" letter from Bayer here in the U.S.

So where is the corresponding letter to health care providers in the U.S. from Bayer about Avelox and its association with liver toxicity?

Further, is the FDA looking at Avelox specifically for serious side effects such as drug-induced hepatitis and liver failure, which seem to be unique to this antibiotic among the fluoroquinolones?

If you have any insight concerning what is going on with Bayer or the FDA about serious adverse reactions to Avelox involving liver toxicity -- ranging from hepatitis to liver transplant -- there are some of us who are curious. 

I would like to hear about what you know regarding this Avelox safety issue.  Of course, I will share that information with our readers; our "source" can choose, however, to remain anonymous (like over at the Cafepharma Message Boards) or not.  Send me an email or submit a Comment, below.  Thanks.

Comments

[Tom Lamb]

Dave:

Thanks for the lead on the web page for the Levaquin MDL. I couldn't get through using your link; here's an alternative URL:

http://www.mnd.uscourts.gov/MDL-Levaquin/index.shtml

As always, your assistance and contributions are much appreciated.

Tom Lamb

[david fuller]

Tom,
Not sure if you were aware of this but thought you would be interested in the fact that with the levaquin multidistrict litigation the court has put on line a website that can be used to follow these levaquin cases:

The Court has created and will maintain a web page devoted to the Levaquin
Products Liability Litigation, which can be found at www.mnd.uscourts.gov/MDLLevaquin.

dave

[Tom Lamb]

Dave:

It's good to hear from you again, even if your report about the Avelox label is "bad" news.

I appreciate the update on Avelox and the comparison to Noroxin (norfloxacin).

As for the Wyeth v. Levine case, we have been watching this pivotal case and trying to bring more public attention to the important public policy issue its presents to the Supreme Court: the possible application of federal preemption legal doctrine to drug injury cases. To that end we have an information page on our Drug Injury Law site where people can learn more about the case:

http://www.druginjurylaw.com/FederalPreemption.php

In addition, I encourage people to visit and vote on this poll question concerning preemption and the FDA, "Who is the FDA protecting: you or the pharmaceutical companies?"; this poll is found at:

http://www.squidoo.com/whoisprotectingyou

I hope you will voice your opinion on the drug injury - preemption issue, there.

Thanks for reading Drug Injury Watch.

Tom Lamb

[david fuller]

Tom,

This is an update concerning these issues as of November 2008:

Well it has been NINE MONTHS since Bayer issued its European Dear Doctor Letter concerning Avelox and we have yet to see one issued here in the states. Nor have we seen the FDA make any mention of the issues raised in this Dear Doctor Letter in ANY of their interviews with the press concerning the FDA’s REQUEST (mind you, this was NOT mandated) that the manufacturers add Black Box Warnings to all the fluoroquinolones drugs. Speaking of which (this Black Box request), it has been five months and we have YET to see any response from the various drug manufacturers regarding this. And still NO Black Boxed warnings.

However we do see some changes in the Prescribing Information and Patient Package Inserts for Noroxin (norfloxacin) (Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- September 2008):

Hypersensitivity Reactions

...Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including Noroxin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

fever, rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson
syndrome);
vasculitis; arthralgia; myalgia; serum sickness;
allergic pneumonitis;
interstitial nephritis; acute renal insufficiency or failure;
hepatitis; jaundice; acute hepatic necrosis or failure;
anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.

The very issues raised in the Dear Doctor Letter concerning Avelox. But even though this is the latest approved update from the FDA you will notice the conspicuous absences of any Black Boxed Warnings of any kind.

In related news, in what has to be the most hotly contested case filed with the current United States Supreme Court this term, the Justices began debating the case of Wyeth vs. Levine on Monday, November 3, 2008. One day before we are to cast our votes for the next president. Wyeth has contended, SUPPORTED by the current Republican administration, that this defective product lawsuit should be thrown out because Federal law preempts such state court claims.

This argument in Wyeth vs. Levine was the latest in an intensifying national debate over “preemption” a doctrine under which companies can be shielded under Federal law from state lawsuits involving any misdeeds by a companies. The drug industry could face massive liability if Levine wins. They would be handed a “Gold Plated” Get Out Of Jail Free card, the same as we have seen the current Republican administration hand out to the manufacturers of medical devices. The manufacturers of medical devices are now EXEMPTED from state lawsuits should their products injure, cripple, or kill a patient provided that had sought and were granted an approval by the FDA. If the FDA approved it and it cripples, injuries, or kills a patient, the manufacturer is to be held harmless. Together with the FDA who you cannot sue for malfeasance.

More than a third of the state product liability lawsuits that this current case would affect have been filed against the drug manufacturers. It does not appear that this issue will be settled before we determine whether the next administration will be Republican or Democrat.

dave

[Tom Lamb]

Charlotte:

Insofar that this is a medical question, and I am only an attorney, I am not in a position to answer.

I suggest you discuss this issue with the prescribing doctor or one of your other doctors.

Thanks for reading Drug Injury Watch.

Tom Lamb

[Charlotte Alford]

After 5 days of Avelox developed severe erthymea and swelling to 70% of body. Is there any treatment for avelox toxicity. How long will it take get out of my system.

[Tom Lamb]

Katelyn:

I'm glad you feel that this article was helpful to you.

Our aim is to get drug side effect information out to those who may need it. As you pointed out, the drug companies don't always do as well as they could when it comes to communicating that aspect of their prescription drugs to doctors and patients.

I wish you the best going forward.

Thanks for reading Drug Injury Watch.

Tom Lamb

[S. Katelyn Garrett]

Came across this website while doing some research on antibiotics that I may be able to tolerate w/out serious allergic reactions or side effects. Have a deficiency of 2 immunoglobulins & don't tolerate most antibiotics. Oddly, I just read what happened to me this past year, while on both Levaquin & Avelox, for an ongoing sinus infection since last Oct.'07. I became so crippled by Dec.'07 that I ended up in a wheel chair due to debilitating pain in the connective tissue of my lt. knee. My daughter accompanied me out of state to a former immunologist. . While there, an EKG revealed some alarming PVCs which had never been problematic before. Last spring I ended up in a local ER when papamedics refused to release me.They were called in after I had suddenly lost consciousness & collapsed on the floor inside a local business. The paramedics stated that I was having too many PVCs & was at risk for a heart attack. This, too, occurred w/in close proximity to more Avelox or Levaquin. I am older & wiser because of God's grace & reading all of the input from this website. "Thank you" for getting this info out to the public! You have most likely saved my life as I am fighting another infection. This time I won't be taking either of these antibiotics & will research alternative treatments. Perhaps it is time for those of us who have these side effects, or have had loved ones who have, to work together to ensure all consumers are "informed" re: this info. This could be done via health care providers, pharmacies & health insurance companies if the manufacturers are not going to pracitice ethically & morally because they are making too much money to have a conscience. They control a great percentage of media, FDA & have much infleunce on those in the medical profession. Unfortunately, they are a political machine out of control & above the law when it comes to consumer protection & our rights to be well informed.

[Raj]

I was lucky with taking cipro, I was diagnosed with a Urinary Tract Infection and the doctor prescripted Cipro. I however, took a few tablets 2-3 doses and felt my muscles hurt a lot, esp my ankles and hamstring. I knew that I didn't like this drug and this was a 10 day regimen I had got. No way was I going to continue to take it for the 10 days with the way I was feeling. I called my doctor and said I am having severe side effects and can you prescribe something else. He did give me something from the pencillin class. I knew that I had taken these as a kid and didnt have a problem with them.

To this day I am thankful I did that, after hearing the horror stories about this drug. But this drug was abused in India in large quantities during the plague scare so god knows how many folks are affected over there.

I am truly sorry to hear some of the stories posted here about the side effects of this drug and how it has affected peoples lives. It should be taken off the market totally and only be used in exceptional cases.

Thanks
Raj

[Tom Lamb]

David:

Once again I much appreciate you taking the time to share with me and others who read this post the detailed findings of your research.

As I indicated in an earlier Comment reply, it seems the EMEA is taking this drug safety issue more seriously than the FDA thus far. Hopefully, as a result of advocacy by you and others, that situation will change in the near future.

Keep up the good work.

Tom Lamb

[Tom Lamb]

Gary:

Good to hear from you, again, on this important drug safety issue.

This detailed report about your Cipro adverse drug reaction should benefit those who are studying the side effects caused by this particular antibiotic as well as others in the Fluoroquinolone class.

Thanks for continuing to read Drug Injury Watch and for participating in the discussion, here.

Tom Lamb

[Tom Lamb]

Shelley:

You may find David Fuller's August 1 Comment about heart problems associated with Avelox use of interest.

Clearly, you have had a most unfortunate experience with Avelox and Levaquin, and from what I have heard from some other readers it appears that you are not the only one.

I hope the FDA is looking at this class of drugs as closely as the EMEA seemingly has been in recent months.

Thanks for reading Drug Injury Watch.

Tom Lamb

[david fuller]

Tom, here is a heads up concerning the heart problems and avelox, from the NDA for avelox:

The applicant selected a HIGHER dose than that approved for clarithromycin for the treatment of CAP. It should also be noted that clarithromycin is NOT approved for CAP due to H. influenzae and therefore may not be the best comparator for the purpose of assessing moxifloxacin efficacy in infections caused by this agent. The use of this higher dose of clarithromycin for CAP CANNOT be used to substantiate ANY potential claims of an enhanced safety profile for moxifloxacin compared with clarithromycin.

The MO reviewed the narratives for patients with serious AES and found that there were two patients who developed empyemas and two who developed worsening of pneumonia whose serious AEs were considered by the applicant to be UNRELATED to study drug. Review of these cases suggested that all three of these patients’s deteriorations WERE related to the study drug. The MO was UNABLE to determine why the applicant considered some clinical deterioration’s attributable and others unattributable to the study drug.

The clinical efficacy of moxifloxacin daily for 10 days observed in this study was comparable to what has been observed with this regime in other studies of CAP. This study DID NOT provide sufficient to support a claim for clinical efficacy of moxifloxacin in the treatment of pneumonia due to S. aureus or K. pneumoniae.

The adverse event and laboratory abnormalities profile seen for moxifloxacin in this study was similar to what was reported from other studies. The applicant presented additional data regarding clinical efficacy in the per protocol population at follow up. Cure rates for each treatment group were 18/33 (54.6%) for moxifloxacin 200 m.g. 19/35 (54.3%) for moxifloxacin 400 m.g. and 61/104 (66.7%) for amoxicillin 500 mg tid. This study DID NOT distinguish between the clinical efficacy of moxifloxacin 200 mg and moxifloxacin 400 mg for the treatment of CAP. It SUGGESTED that moxifloxacin may be similar to amoxicillin 500 mg tid in the treatment of this infection. (NOT SUPERIOR) Hence, the conflicting data presented in the NDA do(es) NOT convincingly support approval of the 7 day moxifloxacin regimen for acute sinusitis indication.

Moxifloxacin clearly prolongs QTc intervals in a concentration-related manner and as a result puts patients at risk for developing malignant arrhytmias. The data provided by the sponsor DID NOT include all patients treated, about 90% were excluded, and ECG were obtained as late as 6 hours after the drug intake (peak concentration is about 2 hours). So the sponsor’s argument that moxifloxacin is safe because it only causes a small increase in QTc is flawed. What was shown in the database is that there are examples of patients on moxifloxacin with changes in QTc intervals greater than 80 msec over baseline with resulting QTc intervals above 500 msec.

In summary, it is hard to justify approving this agent as a first line therapy for non-life threatening infections in which there are a plethora of treatment choices.

Moxifloxacin raises the QTc interval in a concentration related manner and therefore has the potential to cause malignant ventricular arrhythmias, including torsade de pointes, and death. (were do you see this stated in the product label in a black box?)

I recommend approval of moxifloxacin for the treatment of CAP due to S. pneumoniae, H. influenzae, M. catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae.

In conclusion the MO recommends approval of the ten day treatment regimen of moxifloxacin for the treatment of acute sinusitis…drug related adverse events occurred more commonly in the moxifloxacin group (37%) compared to the control group…however the elevation of the prothrombin time, cholesterol and chloride occurred more frequently in the moxifloxacin treatment arm.
*****************
The FDA approved this drug even thought the studies failed to show any advantage over the comprators presented, as well as stating that: Moxifloxacin raises the QTc interval in a concentration related manner and therefore has the potential to cause malignant ventricular arrhythmias, including torsade de pointes, and death.

Even though all of these issues were raised by the advisory committee before hand, and the MO stated that they could not justify the approval this drug, it was approved anyhow...

[Gary Boyles]

I was a fairly normal happy and healthy 51 y/o male enjoying life and full of energy until I took a 10 day course of Cipro to treat a minor UTI. That was 2 years ago. I am now struggling to survive the damage and multiple injuries inflicted on me by Cipro. The cipro did clear up my UTI like any other simple antibiotic would have, but the difference is that Cipro has left me crippled and in intense pain 24/7. Cipro damaged my joints,tendons,nerves in feet and legs and has done CNS damage that gave me insomnia,anxiety and depression. I just received my lab tests recently and they now show that I have Diabetes insipidus as well. I traded a simple UTI that could have been cleared by any number of simple and safe antibiotics, but since Dr's have been using the fluoroquinolones like Cipro as a first line treatment for these minor infections, I now have all these health problems, including a life threatening condition, all brought on by Cipro. Basically, Cipro has destroyed my health and ruined my life. The new warnings on FQ ABX are way too weak and way overdue. The FQ class of ABX is extremely toxic and dangerous. I now feel like my life is over and I am living on borrowed time. Every day is a struggle to get through and there is no sign of improvement. The victims injured by these toxic drugs live with the daily horror of what has happened to them and would give anything to be able to go back in time and not have let their ignorant Dr. poison them. Every day I think about all the others suffering like me and the new unsuspecting ones yet to be poisoned. Something has to be done to stop this insanity and waste of human life. That weak Black Box warning only covers tendon rupture and doesn't list all the real dangers associated with the FQ's. I only wish that my Dr. had warned me of all the possible side effects and I would have taken something else and not be in this daily hell. Gary TBY

[Shelley Sealover]

Please allow me to C&P part of my comment. The only thing I have to add is the fact that I have been diagnosed with yet another fluoroquinolone-induced condition: Premature Ventricular Contractions

I have recently had to wear a holter monitor overnight, but do not have the results yet.

Besides the monitor, I’ve also just had an X-ray of my neck, which has been causing severe pain lately. I am hardly able to hold up my head.

I have previously had 2 sets of X-rays done on my hands and feet, and an MRI of my head. My entire body is in pain from the bottoms of my feet to the top of my head.

I was previously healthy and active, enjoyed working out, and even jumping on the trampoline w/ my boys on a daily basis. Now I can hardly move. An "antibiotic" caused this.

Every morning when I open my eyes, I awaken to this nightmare. There is a “sickness” that feels like my body has been poisoned. My hands and feet are swelled and sore…my entire body is stiff and painful…heart-palpitations, vibrations throughout my body…ringing in my ears…bleeding specks of sores on my skin…and a full, bloated feeling in my gut…I feel like I should be dead. It is only by the grace of God, and the love of my 2 children that I am able to pull myself up out of bed, and make it painfully down the stairs. Crying will do no good, as I know I must be strong to fight this horrendous ordeal that has become my life. Knowing that there are others who are living this nightmare gives me a sense of strength…and compassion. There are no more words to described what we are going through emotionally, let alone physically. How could something so unbelievably criminal have happened to us?? And why is this insanity being allowed to continue?? How many more innocent people will have their lives destroyed…how many more must suffer…how many more must die….before something is done?? Someone tell me, what will it take??

Diagnosed w/ arthralgia, trigeminal neuralgia, tendinitis both elbows, enlarged lymph nodes…
still seeing doctor after doctor, and specialists who can only treat the “symptoms”, not the cause.

The Black-Box warning for tendon damage is hardly sufficient and long-overdue.

The poisons that robbed my children of a mother were AVELOX and LEVAQUIN…20 pills. I traded a sinus infection for this life of pain and misery.

Thank you for helping to expose the truth about this deadly class of "antibiotics".

[Tom Lamb]

I am not as familiar with the cardiac side effects of Avelox as I am with the liver toxicity reports.

Coincidentally, a couple of days ago the European drug regulators were asked by an advisory panel to restrict the use of Avelox due to the serious side effects associated with this alleged "unsafe" antibiotic from Bayer. Here's a link to my article about this Avelox news:

http://www.drug-injury.com/druginjurycom/2008/07/avelox-eu-agency-recommends-restricting-moxifloxacin-use--thu-jul-24-2008-759pm-bst--frankfurt-july-24-reuters---the-eu.html

Thanks for reading Drug Injury Watch.

Tom Lamb

[Andrea Campbell]

In March 2008 I was prescribed Avelox for a minor sinus infection. After 3 doses I stopped because of the following symptoms: fever to 101, tingling in feet, dizziness, faintness, nausea, acute gastritis, and blood in urine. However, the worst event coincidental with taking this antibiotic was diagnosis of atrial fibrillation. I am considered to have lone AF, meaning no apparent cause and no other health risks involving my heart. I had never had any heart problems in my life. Echocardiogram and nuclear stress test showed no other heart issues. I am convinced Avelox caused this condition that will plague me for the rest of my life. Furthermore, I now seem to be having degeneration of my muscle strength in my lower back and legs. A month before Avelox, I was healthy and active. Now I can't even stand up without help from my arms to push up. Sooner or later, the risk to the heart will be added to the black box warnings, but I'm sure it will be far too late for many other unfortunate patients.

[Tom Lamb]

You are certainly correct that prescription drug adverse reaction events are under-reported in the U.S., which is unfortunate.

The idea that this phenomenon may be especially true with this class of antibiotics seems highly probable due to the diverse set of side effects you mentioned, as opposed to a drug having one "signature" side effect such as digoxin toxicity (with the recalled defective "double-dose" Digitek pill, for example).

I expect there others who have a similar position about this antibiotic drug safety issue.

And others may disagree....

Thanks for reading Drug Injury Watch.

Tom Lamb

[Gary Boyles]

The number of side effects and the seriousness of these side effects caused by this class of antibiotics is grossly underrated and under-reported. Tendon damage is only one of the many injuries these drugs inflict on thousands of people each year. The delay in time between taking these drugs and having the adverse reactions present is what has concealed the high number of reactions. Most Dr's do not even realize that the tendon, nerve, muscle and CNS injuries that their patients develop after taking Fluoroquinolones is related to the antibiotic.

The true number of people affected each year by these antibiotics is astounding and has been well hidden by the manufacturers. There are thousands of people that have been permanently crippled and hundreds of thousands more that have suffered the ADR's of Fluoroquinolones for months to years.

I can only say that this Black Box warning is way overdue and still doesn't cover many of the other severe and disabling side effects these drugs inflict.

I was healthy prior to taking cipro 2 yrs ago. For the last 2 yrs. I have been in constant pain with CNS problems also. These drugs are far too toxic and dangerous to use so freely. My life has been ruined by Cipro.

Gary TBY

[Tom Lamb]

I appreciate you taking the time to share your unfortunate experience with us.

As you are aware, there are many people who are critical of this class of antibiotics due to serious side effects associated with their use.

In order to let the FDA know about medical conditions that may be caused by Avelox, Cipro, Levaquin, etc., reports of serious side effects should be made to the FDA's MedWatch program.

Here are links to some pages at our web site, Drug Injury Law, which will tell you about the FDA's MedWatch program and how to submit a report:

http://www.druginjurylaw.com/drug-injury-reporting.html

http://www.druginjurylaw.com/medwatch-report.html

Thanks for reading Drug Injury Watch.

Tom Lamb

[Deathby Cipro]

I have a ‘constellation’ of permanent injuries (adverse reactions) that I developed from a week of taking Cipro in 2006, including tinnitus, hyperacusis, hyperlipidemia, visual distortions, insomnia, chronic fatigue, generalized pain, anxiety and severe depression, peripheral neuropathy, in addition to the muscular and degenerative bone issues. Tendonitis is only a small fraction of the damage done by Cipro. All of the ADR's I sustained are listed on either Cipro or Levaquin PI sheets but with the exception of the neuropathy, no where does it say it can become permanent (irreversible). The first ENT I saw wrote it off to Meniere’s disease, although I have no vertigo, and a doctor at a major hospital said "you don't have Meniere's but I have no idea what it is". At least he was honest. Dozens of other doctors and thousands of dollars of tests later, doctors write it off to depression and anxiety except for the documented degenerative bone loss that shows up on CT scans. No prescription has helped with the insomnia, anxiety or depression and actually makes it worse. No supplement or food makes it better. Eating makes me feel sick. I was a healthy 52 year old before this, but every day only gets worse. Yes, none of these symptoms are fatal, nor will any doctor put me in a hospital for treatment (except for depression, which has been untreatable). The original doctor who prescribed this medicine for me after a 'routine' colonoscopy to prevent infection also can’t explain why I have all these symptoms, and after a perfectly 'ok' colonoscopy I also have severe constipation and all sorts of GI problems after her procedure. Also ADR's listed on the Cipro PI. But no cancer. Yet. The FDA needs a person to read the data - or perhaps the data isn’t getting recorded - but one thing is for sure - if people read blog entries like these, and there are blogs all over the Internet proving these drugs have serious and permanently debilitating ADR's someone should wonder what is going on with these quinolones. Tendons are the tip of the iceberg.