20 responses to “February 2008 “Dear Doctor” Letter About Avelox / Avalox Is Sent By Bayer In Europe”

1. 

   david t fuller

   February 21, 2008

   “We will watch for any similar Avelox “Dear Doctor” letter from Bayer here in the U.S.”
   I am very doubtful that we will ever see such letters from Bayer here in the U.S. Any number of “Dear Doctor” letters have been issued overseas regarding this class, some as early as the mid nineties, that were never sent here.
   Even though we have been working for almost eight years now to add “Black Box” warnings as well as “Dear Doctor” letters we continue to be stymied by the FDA. Public Citizen filed suit in January of 2008 in Federal Court to compel the FDA to even consider such a petition that Public Citizen had filed. Nor has the FDA considered a similar petition filed by the Attorney General of the State of Illinois.
   The side effects to Avelox, as well as the rest of the drugs found within this class, are horrendous (full documentation can be found on http://www.fqresearch.org) and this letter makes no effort to address all of these severe and crippling adverse reactions either.
   If you have any hopes of seeing such a letter sent here in the United States do not hold your breath. You will die from lack of oxygen. As we have seen with Bayer’s blood thining drug they will drag their feet as long as possible. And the FDA has no interest whatsoever in forcing Bayer to do anything else.
   The best we can hope for is that the Foundation acquires a copy of this letter so it can be posted on the research site.
   Regards,
   Mr. David T. Fuller
   Director
   Fluoroquinolone Toxicity Research Foundation
   http://www.fqresearch.org

   Reply
2. 

   Tom Lamb

   February 22, 2008

   If anyone has or gets a copy of the Avelox “Dear Doctor” letter sent in Europe please forward a copy to me and David Fuller, of the Fluoroquinolone Toxicity Research Foundation (his contact information is in Comment below).
   Further, please report any serious skin reactions or liver problems associated with the use of Avelox to the FDA MedWatch program and, if you want, let me know about your Avelox side effect experience.
   Thanks for reading Drug Injury Watch.
   Tom Lamb

   Reply
3. 

   Brian Nix

   February 22, 2008

   You can not say that the entire class of drugs has horrible side effects. Levaquin and Cipro are both renally excreted, which has allowed them both to stay away from the hepatic issues seen in most other quinolones. Avelox is just another “potent” but dangerous quinolone on the market and American doctors should be aware of the danger when prescribing this terrible drug! Why doesn’t Bayer send this letter to every physician?

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4. 

   Tom Lamb

   February 23, 2008

   I imagine one reason that Bayer would not want to send a new “Dear Doctor” letter about Avelox is that Bayer would rather not emphasize the important distinction which you point out to us.
   Thanks for reading Drug Injury Watch.
   Tom Lamb

   Reply
5. 

   Mr. David T. Fuller

   February 28, 2008

   “You can not say that the entire class of drugs has horrible side effects.”
   With all due respect toward Brian Nix I most certainly can with confidence, as I have forty years worth of documentaion to base such a statement upon, main stream documentation I might add, that proves this to be a fact.
   I do not wish to argue the point but all one has to do is log unto the research site at http://www.fqresearch.org and read the 4000 plus medical journal entries, clinical studies, case reports, etc., the clearly documents the harsh reality regarding the toxicity of this entire class.
   Additionaly the statements made by Mr. Nix are grossly in error.
   Avelox is also renally excreted, contrary to Mr. Nix statements. Approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate (M2), which is excreted exclusively in the urine.
   Cipro however is NOT excreted exclusively in the urine as Mr. Nix claims, again in error, but also through feces and is indeed processed through the liver.
   Concentrations of ciprofloxacin are several folds higher in the bile than serum concentrations after oral dosing. Approximately 40-50% of an orally administered dose is excreted in the urine unchanged. The urinary excretion of cipro is virtually complete within 24 hours after dosing. An additional 1-2% of the dose is recovered from the bile in the form of metabolites. Approximately 20-35% of an oral dose is recovered in the feces with 5 days after dosing. Only approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate
   (M2), is excreted exclusively in the urine.
   Levaquin is also not excreted exclusively through the urine but also through the feces. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hours, 4% of the dose was recovered in feces within 72 hours.
   Strange how the bile concentrations are so high for cipro, yet Mr. Nix states it is not processed through the liver.
   The information I just presented was taken directly from the package inserts for all three drugs being discussed.
   Mr. Nix should also take note that Health Canada is also taking a SERIOUS look at liver toxicity and levaquin, going so far as to solicit physicians for such reports.
   Liver damage has been reported with both Cipro and Levaquin and just about EVERY other fluoroquinolone drug. You will find about a hundred such reports on the research site.

   Reply
6. 

   Tom Lamb

   February 28, 2008

   Thanks for sharing this summary of your extensive research into the fluoroquinolone class of drugs and expressing your position on this issue.
   Perhaps Brian Nix, or one of other readers with your level of background and knowledge, will want to continue this discussion about liver toxicity being unique to Avelox / Avalox or liver toxicity being a so-called “class effect”.
   We hope you will check back here to see whether we have more comments on this particular post and, more generally, that you keep reading Drug Injury Watch.
   Tom Lamb

   Reply
7. 

   David T. Fuller

   March 13, 2008

   Tom,
   Thought you might have an interest in what the drug reps here in the States are saying about this European “Dear Doctor Letter”
   http://www.cafepharma.com/boards/showthread.php?t=257508
   Not encouraging in the least.

   Reply
8. 

   Tom Lamb

   March 13, 2008

   I very much appreciate you leading us to this online discussion by the Avelox sales reps and others about how the adverse events (AEs) that have been associated with Avelox make their task-at-hand more “complicated”, at least.
   Whether the change to the Avelox / Avalox package insert in Europe is the beginning of the end for Avelox sales — or even an Avelox recall — in the United States remains to be seen.
   The issue of whether the label change in Europe simply means that the Avalox (EU) warnings are now the same as the Avelox (US) warnings is something I hope we can have some more discusion about, here.
   Any and all are welcomed to weigh-in on this important debate about whether or not Avelox is an unsafe drug.
   Thanks for reading Drug Injury Watch.
   Tom Lamb

   Reply
9. 

   david t fuller

   March 13, 2008

   “The issue of whether the label change in Europe simply means that the Avalox (EU) warnings are now the same as the Avelox (US) warnings is something I hope we can have some more discussion about, here.”
   I hate to be the only one commenting on this but the current label in the United States (2/2008) makes NO mention of potentially fatal liver reactions other than the following buried in the “fine print”
   “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 AVELOX. 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 drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or
   any other sign of hypersensitivity and supportive measures instituted.”
   It even goes further to state that :
   “The pharmacokinetics of moxifloxacin in severe hepatic insufficiency (Child Pugh Class C) have not been studied.”
   The label can be found on the FDA site by following this link:
   http://www.fda.gov/cder/foi/label/2008/021085s038,021277s031lbl.pdf
   As such I would assume that the European label has a much stronger and clearly defined warnings regarding this. I have not been able to acquire the European label as of yet to determine this. If not then it is just as useless as the one currently employed in the United States as we find mention of possible liver damaged buried within ALL the labels for drugs within this class and have done so for years now. I may not be the brightest bulb on the tree but I continue to fail to understand is WHY (rhetorically speaking) we would even have different warnings for different countries. Either the drug has the potential to cause such a problem or it does not. You would think that a label change would be a universal change, but alas this is not the case. Those countries with lax enforcement or sub standard regulations appear to be the reason for this. The manufacturers choose to only reveal what they are forced to reveal. Nothing more and nothing less. And as we have seen, this “rule” also applies to those responsible for selling their products.

   Reply
10. 

    Tom Lamb

    March 14, 2008

    Does anyone have a copy of or link to the February 2008 warning letter sent to doctors in Europe about the antibiotic Avalox?
    Perhaps one of our pharmaceutical company readers — who have taken a notable interest in this particular article during recent weeks — can help us?
    As Mr. Fuller points out, it would be good to see whether the Avalox label change in Europe, which reportedly was intended to emphasize severe liver reactions and serious skin rashes, is simply catching up the EU to what has been on the US Avelox label, or if the new Avalox label in Europe has, in fact, added a stronger warning about these serious side effects that can be caused by Avelox use.
    A thanks in advance to that “someone” who can help us out so that we can make this Avelox / Avalox label comparison and share it with our readers.
    I hope you will continue to read Drug Injury Watch, and see what we learn.
    Tom Lamb

    Reply
11. 

    Tom Lamb

    March 14, 2008

    We have found the February 2008 “Dear Doctor” letter for Avelox sent in Europe.
    It is titled “Direct Healthcare Professional Communication regarding moxifloxacin (Avelox®) and serious hepatic and bullous skin reactions”.
    It starts with this text: “In agreement with EU regulatory authorities, including the Medicines and Healthcare products Regulatory Agency (MHRA), Bayer would like to inform you of important safety information. A recent assessment of adverse reactions associated with the use of moxifloxacin resulted in the following information and recommendations….”
    The final version of the letter can be viewed at:
    http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con014103.pdf
    What appears to be an earlier draft of this letter can be viewed at:
    http://www.cbg-meb.nl/NR/rdonlyres/40FA65BB-64F8-46AA-9027-2FB4521FAA5C/0/DHPC20080208_Avelox_UK.pdf
    We still need to determine if there are distinct “EU” and “US” versions of the Avalox / Avelox package insert and, if so, whether they differ in terms of the warnings about the serious liver problems and the SJS and TENS-type skin reactions.
    Thanks to the person who provided us with the links to these letters, above.
    Tom Lamb

    Reply
12. 

    david t fuller

    March 14, 2008

    Tom,
    Using the following information it appears that we have determined that there are not distinct “EU” and “US” versions of the Avalox / Avelox package insert and, that they do not differ in terms of the warnings about the serious liver problems and the SJS and TENS-type skin reactions.
    This appears to only be a case of when the document was actually filed in Europe.
    From the following it appears that there is no difference at all:
    According to the FDA records contained on the FDA site:
    http://www.accessdata.fda.gov/scripts/cder/drugsatfda/
    There have been two label changes in the United States. The latest being on 02/15/2008 and the other on 5/31/2007. The label change of 5/31/2007 makes reference to the liver and SJS/TENs issue we are discussing, to wit:
    “These “Special Supplement – Changes Being Effected” supplemental new drug applications provide
    for revisions to the package insert for Avelox® to ensure consistency in the communication of the risks
    of acute liver failure and acute severe liver injury, QTc prolongation/torsades de pointes, tendon
    rupture, toxic epidermal necrolysis (TEN), and Clostridium difficile associated disease (CDAD) with
    the use of antimicrobial products, including moxifloxacin.”
    Here are the additional liver warnings (2 and 7):
    “2. The seventh paragraph in the WARNINGS section (the second paragraph regarding
    hypersensitivity) was replaced with the double underlined text below to provide greater clarity
    in the grouping of hypersensitivity findings. A subsection heading of Hypersensitivity
    Reactions was added before the sixth paragraph. This subsection reads as follows:
    Hypersensitivity Reactions
    Serious anaphylactic reactions, some following the first dose, have been reported in patients
    receiving quinolone therapy, including AVELOX. Some reactions were accompanied by
    cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea,
    urticaria, and itching. Serious anaphylactic reactions require immediate emergency treatment
    with epinephrine. AVELOX should be discontinued at the first appearance of a skin rash or any
    other sign of hypersensitivity. Oxygen, intravenous steroids, and airway management,
    including intubation, may be administered as indicated.
    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 AVELOX. 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; leucopenia; agranulocytosis; pancytopenia; and/or other
    hemotologic abnormalities.
    The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or
    any other sign of hypersensitivity and supportive measures instituted
    7. Under the ADVERSE REACTIONS/Post-Marketing Adverse Reactions subsection, the
    following events were included:
    a. hepatic failure, including fatal cases
    b. toxic epidermal necrolysis”
    The following text in () was removed:
    (Severe and sometimes fatal events, some due to hypersensitivity, and some of uncertain
    etiology, have been reported in patients receiving therapy with all antibiotics. These events may
    be severe and generally occur following the administration of multiple doses. Clinical
    manifestations may include one or more of the following: rash, fever, eosinophilia, jaundice,
    and hepatic necrosis.)
    So basically all they did was REMOVE the previous portion that stated:
    “Clinical manifestations may include one or more of the following: rash, fever, eosinophilia, jaundice,
    and hepatic necrosis” from the the ‘Hypersensitivity Reactions’ section and added the statements “hepatic failure, including fatal cases” and “toxic epidermal necrolysis” under the ‘Hypersensitivity Reactions’ section instead of keeping the previous text. Kinda like three card monty. Now you see it and now you don’t.
    In my opinion this so called “update” did absolutely NOTHING to increase the awareness of such potentially life threatening liver damage. And in fact it appears to have TRIVIALIZE it rather than emphasize it.
    The latest label change, 2/2008 simply repeated the previous warnings concerning photosensitivity/phototoxicity which once again did nothing to draw attention to this adverse event other than clarifying that this may occur with moxifloxacin.
    “These “Special Supplement – Changes Being Effected” supplemental new drug applications provide
    for revisions to the package insert for Avelox® to ensure consistency in the communication of the risks
    of photosensitivity/phototoxicity with the use of fluoroquinolone products, including moxifloxacin.”
    When we follow this link which appears to be the label insert that Bayer is referring to have been updated in the fall of 2007 we find the exact wording found within the 5/2007 label change recorded on the FDA site:
    This has to be one continous string with no blank spaces in your browser window so you may have to cut and paste the pieces back together:
    http://www.univgraph.com/bayer/inserts/avelox.pdf
    (this is the 10/2007 label being referenced by Bayer in their Dear Doctor Letter)
    Judging by this information it appears that the label was FIRST changed back in 5/31/2007 with out any fanfare of any kind regarding the potential of liver damage, no “Dear Doctor Letters”, no press releases, nada, and then later updated over in Europe five months later on 10/2007. As such it appears that Europe is playing catch up with the label approved in the United States five month earlier. There does not appear to be two separate labels, but rather the same label being filed at different intervals (5/2007 in the United States) and (10/2007 over in Europe). There is no record to be found within the FDA database regarding a label change taking place 10/2007 that I can find. So we will now see how long it takes for Europe to catch up with the phototoxicity warnings that were updated on 2/2008 here in the States.
    Curious that they did not issue any “Dear Doctor Letters” back in May of 2007 when they updated this warning but now are doing so for a label that was filed in Europe though they appear to be the EXACT same label and contain the exact same warnings.
    Here it the full link to the FDA page where this information is posted.
    This has to be one continous string with no blank spaces in your browser window so you may have to cut and paste the pieces back together:
    http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails

    Reply
13. 

    Tom Lamb

    March 15, 2008

    David,
    Thank your effort and time in figuring out for us this sequence of events.
    Of course, this issue remains open for debate: Is Avelox an unsafe drug?
    I hope you, and others, continue to participate in our discussions here at Drug Injury Watch.
    Tom Lamb

    Reply
14. 

    david t fuller

    March 15, 2008

    Of course, this issue remains open for debate: Is Avelox an unsafe drug?
    In my opinon the answer to this questions is definative “Yes” And I believe the FDA felt the same way but approved it anyhow:
    Avelox: Nov. 1997 – June 5, 2007
    Total reactions: 30,160
    Total death outcomes by case: 337
    Total individual safety reports: 7,391
    Levaquin Nov. 1997 – May 30, 2007
    Total reactions: 39,128
    Total death outcomes by case: 806
    Total individual safety reports: 9,711
    Avelox volume: 50 million, Levaquin volume: 530 million. Let us do the math.
    Even though it had been claimed that 530 million scripts have been written for levaquin we only see 39,128 reported adverse events. That would equal to about a 1 in 13,500 chance of having a reaction.
    50 million for Avelox and 30,160 reported events. That would be about a 1 in 1,600 chance. So which is being claimed as the “Safer” drug here?
    A patient has a thousand percent greater chance of having a reaction based upon these numbers than it’s closest competitor, Levaquin. What does all this prove? Exactly what those patients who have suffered these reactions have stated. The adverse reactions are grossly under reported and the manufacturers screw with the numbers to make their product shine.
    Within the package insert it is stated that:
    “Moxifloxacin was discontinued due to adverse reactions thought to be drug-related in 2.9% of
    orally treated patients and 6.3 % of sequentially (intravenous followed by oral) treated patients.”
    Ok, let us do some math again, using the worse case scenario. 50 million time 6.3% equals 315,000 reactions NOT 30,160 we see reported to the FDA. That changes things dramatically doesn’t it? Now the odds have changed to a 1 in a 160 chance of having a reaction rather than a 1 in 1600 and 90% of these reactions were never reported to the FDA.
    Wait, it gets even worse. When we review the NDA for Avelox these numbers increase dramatically yet again. For example in study D96-024,
    (http://www.fda.gov/cder/foi/nda/99/2…ox_medr_P8.pdf)
    submitted with the NDA comparing Gatifloxacin with Avelox look what we find:
    75% efficacy with Avelox vs. 88.7% efficacy with the compactor. Both the sponsor and the FDA analysis of this efficacy data failed to demonstrate the equivalency of Avelox at 400 / 7 days compared to the compactor at 250/10 days. In fact the compactor won this round. And 51% of the Avelox patients suffered an adverse reaction as compared to 41% of the compactor.
    Note that these reactions are not “tummy aches and nausea”, but sufficient to warrant STOPPING the drug.
    On a side note the compactor used in the above study is no longer manufactured by Bristol-Meyers Squibb, (May 2006) due to severe and fatal adverse reactions. (fatal hypo-hyperglycemia) Yet even when compared to this toxic drug Avelox had a greater incident of adverse events.
    Now we are looking at a fifty / fifty chance of having an adverse reaction verses a 1 in 1600.
    Since we are talking about massaging numbers lets take a look at another example of this corruption we find:
    Within the 2008 label it is stated that:
    “No cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin treatment in over 9,200 patients in controlled clinical studies.”
    But again what the label DOES NOT STATE is the fact that the sponsor provided data to the FDA that showed that Avelox on average only prolonged the QTc about 4 msed but forgot to mention that about 90% of the patients were EXCLUDED from this evaluation and that the ECG was obtained as late as 6 HOURS after the drug intake. (peak concentration is about 2 hours).
    What WAS shown within this database is the fact that changes in QTc intervals greater than 80 msec over baseline with resulting QTc intervals above 500 msed.
    In this summary, it was stated in the NDA, that “it is hard to justify approving this agent as first line therapy for non life threatening infections in which there are a plethora of treatment choices.”
    Even the advisory committee felt the same way and stated this on the record. But non the less it was approved. With an adr rate of 51% found in one submitted study.
    Is Avelox unsafe? When we add in the latest liver problems, SJS and TENs to the pre-existing cardiovascular problems, spontaneous tendon ruptures and irreversible peripheral nueropathy, as well as taking into consideration of the horrendous safety profile of this class, this is a no brainer. Nothing more than the latest DNA experiment gone horribly wrong. But will this result in it being removed from clinical use in the United States? Again another no brainer, the answer is no, it will not.
    The drug has by now generated sufficient profits to handle any ensuing lawsuits with a more than tidy profit left over.
    Even the drug reps share this opinion:
    “Everytime I con a doctor into writing this piece of shit drug, I realize how great a salesperson I really am.”

    Reply
15. 

    Tom Lamb

    March 17, 2008

    Thank you for pulling together these insightful facts.
    This analysis should raise some eyebrows and prompt further discussion about the safety of Avelox.
    Tom Lamb

    Reply
16. 

    david t fuller

    March 18, 2008

    Excerpts from the Anti-Infective Drugs Advisory Committee 67th Meeting 1999
    QUOTES FROM THE HEARING:
    Committee Doc A: I’m going to say no, and I’m going to say no because of the following reasons. I think when the drug is marketed,
    no matter what kind of warning you put in it, t’s going to be used in substantially different ways than it’s been used in the trials. And, I think that this is exactly the kind of place that you get into trouble with,
    when a drug is approved, it’s carefully studied in a trial, people are carefully excluded who have prolonged QT intervals, are carefully
    excluded who are on drugs that can be additive with it in terms of the effect, and it’s used for a very short interval of time, and so it’s not clear — I am absolutely convinced
    that the drug will be used differently once it’s marketed frequently.
    And, I think there are enough things that really haven’t been answered. I don’t know if the drug effects potassium and magnesium excretion, and whether it somehow is additive with other drugs that produces increased loss of electrolytes through the kidneys, because that has not been looked at. It seems to possibly cause or increase
    the incidence of atrial fibrillation, and we don’t have real drug levels from real patients correlated with QT times. So, I don’t know, I’m just somewhat concerned. The other issue with safety, obviously, is the risk benefit ratio, and I’m not sure I see what this drug adds to drugs that we already have that’s so unique that we need this drug, that we
    absolutely need it, and we need it now for some indication. There are
    other drugs that you can use. They may have the same problem, but given that they haven’t been studied in this way, I don’t know that’s the case.
    ——
    COMMITTEE DOC B: Well, I guess I’d have to say no, the data on safety are not convincing. It seems to me, based on the discussion, that the QT facts are clinically relevant, steady state
    concentrations needs to be studied further. In addition, the concern
    about people using the drug for longer than 12 days, I don’t think we
    have enough information on that, and I believe that that may occur, even though that probably would not necessarily be what
    we would recommend.The other concerns about other drugs that might prolong the QT interval, the problems with hypokalemia, the problems with death after the drug was discontinued, and, again, the age-old problem, the use of this drug in children, I think we need to study the drug and the pharmacokinetics, and we also need to study the
    safety in the pediatric population. We need data on that, because although it was not studied, and although it won’t be
    approved for children, I’m afraid it will be used in this population and I’m concerned about that.
    << COMMITTEE DOC C: I was prepared to vote for safety with an appropriate change in the label, but the two that have talked about all the things that we don't know about, you know, the behavior of this drug have swayed me. I think I shall have to vote against, I don't believe we know enough yet about the safety because of the cardiac problems.--------- Guest Expert Doc A: I was -- I thought Dr. A's summary captured a lot of my concerns, and I think that on balance we don't know enough now to conclude that it's safe.I think the other thing that gives me pause is the fact that this is a drug that may be very widely used, so even if the estimates of one to two percent, which I think are very conservative, of meaningful QT prolongations are correct, that might be tens or hundreds of thousands of people who would experience those. So, it seems to me that knowing more would be necessary for me to say yes, so I think if I had a vote I would probably say no for now. ACTING CHAIRMAN : And finally, I'd like to make sure that there are no other comments that the voting members of the committee would like to make. Committee Doc D: I just have one comment, which also echoes a little bit what Dr. A said, which is that although I think this drug is safe, I think we also have to consider the other drugs, other antibiotics that are out there, and whether the risk benefit ratio is as good as other comparators or similar drugs that are there. And, I think in balance this probably doesn't add a terrible -- it doesn't add very much to the antibiotic armamentarium that we currently have. ------ Dr. A: I'm a little confused by what we are voting on. I mean, my answer is still no from before. I agree that if the drug is approved that it has to have a warning label similar to what's been described. I also wonder whether it shouldn't include something about the possibility that it may induce atrial fibrillation in patients, particularly, patients at high risk for that arrhythmia. And, you know, whether it should contain information about the drug effect on QT may be aggravated by hypokalemia and, therefore, potassium levels, particularly, on patients who are on drugs that cause hypokalemia should be monitored, or at least baseline checked.I mean, I think there may be other things that need to go into the warning label to caution people. I would also suggest that it say something about the fact that in the trials prolonged use of the drug, in terms of its cardiovascular safety, were not assessed, you know, by giving it longer than stated You know, in terms of the other drugs that have been approved, I guess one of the problems that the pharmaceutical company has here is that, you know, they were, perhaps, the first to come along, take a drug with this issue and evaluate it so thoroughly, so it's probably, you know, raised as many questions as it has answered. DR. A: Do you have data on how this drug affects potassium and magnesium excretion from the kidney? The second question, in terms of the accumulation of this drug in tissues, over what time period does that occur? What is the half life in tissues? Is it likely if people use the drug for longer periods of time that the drug would continue to accumulate and levels would continue to rise in tissues? DRUG CO. DOC: We do have some tissue accumulation studies in Phase I and Phase II and in small numbers of patients multiple time points. We also have a dialysis and skeletal muscle study. Most of those studies, however, were done with a single dose administration of very short term.There is, as Dr. __showed you, considerable accumulation in pulmonary tissues which is helpful in this sort of setting. Our data for skeletal muscle is that the concentrations reached in skeletal muscle are about 80 percent of the plasma concentrations of the drug. We don't have data to address the possibility of long-term accumulation in tissues but for skeletal muscle the ratios are less than plasma concentrations. ------- So less than 8 weeks after this hearing where all these issues were raised, it was approved. All of those who claimed to be inclined to vote "NO", changed their vote to "YES".

    Reply
17. 

    Tim Beck

    January 3, 2009

    I took Avelox in the spring of 2008 for a sinus infection. After taking the medication for 3 weeks, my liver shut down from the inability to metabolize it further. I was on bedrest for 3 weeks afterward. As of today, I have been diagnosed with permanent nerve damage in my ears with a medium loss of hearing. The doctor believes this is a further side effect from the Avelox in my system. Was this letter or notification sent out in the US? I know there was an emergency bulletin sent out to doctors about 2 weeks after I had been taking the medication, but didn’t find out about it until my liver had shut down and I visited a specialist. Any information you can give would be helpful. Thanks. Tim

    Reply
18. 

    Tom Lamb

    January 5, 2009

    Tim:
    I appreciate you taking the time to let us know about your unfortunate experience using Avelox.
    There was no Avelox “Dear Doctor” letter sent in the U.S. similar to the one which Bayer sent in Europe regarding Avalox (to my knowledge).
    I am aware of the liver damage side effect reports, generally, that have been associated with Avelox use, but had not heard previously about hearing loss as a secondary effect.
    I hope you have a better year in 2009.
    Thanks for reading Drug Injury Watch.
    Tom Lamb

    Reply
19. 

    Sam Donato

    March 26, 2009

    Good Morning Mr.Fuller
    I had one capsule of Avalox and ten minutes later i was itching all over and the tommy ache with diarrhea. I could not swallow I had palpitations and my eyes were injected red and I had fever my face and arms were swollen as if I had sunburn.I had an injection of Solucortef 100mg and Aerius 5mg.Best regards.Sam Donato

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20. 

    Tom Lamb

    March 26, 2009

    Sam:
    It sounds like some type of allergic reaction to this medicine. Is that what your doctor(s) said was the cause of your medical condition?
    Thanks for reading Drug Injury Watch.
    Tom Lamb

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