# FDA calls for urgent warning on tendon risks



## Tina (Jul 8, 2008)

I've been taking this for a bladder infection, IC flare-up. Scary.
*FDA calls for urgent warning on tendon risks*

By RICARDO ALONSO-ZALDIVAR, Associated Press Writer Tue Jul 8, 11:23 AM ET

WASHINGTON - Federal drug safety officials have imposed the government's most urgent warning on Cipro and similar antibiotics, citing risks that they can cause tendon ruptures, a serious injury that leaves some patients incapacitated. More...


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## Miss Vickie (Jul 8, 2008)

I read about this today. It's very concerning, particularly since I'm on a high dose, 14 day dose of Cipro for a kidney infection. I'm still trying to work out how an antibiotic can cause a tendon rupture; that just seems so random. But it just goes to show that nothing is benign.


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## Tina (Jul 8, 2008)

Yeah, I couldn't figure out what the correlation might be, either. Weird.


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## Half Full (Jul 9, 2008)

I believe it has something to do with the mechanism of how the drug causes the cell membrane of the bacteria to rupture in order to kill it and for some reason tendon/connective cells seem to be very vulnerable as well.

I can tell you that I took Levaquin for the first time about six weeks ago ago (before all these warning were issued) for a recurrent soft tissue infection *as a palliative measure* to make sure the infection was "wiped out" completely. (I had a course of Keflex and still had some tenderness so my doc wanted to take care of it once and for all) 

I read the warning insert but at the time the tendon rupture and associated symptoms were listed as "rare occurrences" so I really didn't put too much stock in worrying about it.

After 3 doses - THREE! I had such severe vomiting I actually thought I had ruptured my stomach. I never had pain like that in my life! I really expected to be puking up blood at any moment and should probably have gone to the ER but it was the middle of the night and frankly I was too miserable to think straight. I also developed severe knee pain and have tingling and numbness in my feet that I never had before taking the Levaquin! It is getting better but it is still a reality!

I never thought I could have such a dramatic adverse reaction after only 3 doses (500mg daily - smallish dose especially in realtion to BMI  ) but this drug is wicked bad - avoid it at ALL COSTS! 

Vicki, please monitor for *any* symptoms closely and frankly, if I were you I would see if there isn't a different antibiotic you can switch to!


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## saucywench (Jul 9, 2008)

Here's the whole schmoo:






*FDA News*

*FOR IMMEDIATE RELEASE*
July 8, 2008
*Media Inquiries:* 
Christopher Kelly, 301-827-6242
*Consumer Inquiries:* 
888-INFO-FDA 


*FDA Requests Boxed Warnings on Fluoroquinolone Antimicrobial Drugs*
*Seeks to Strengthen Warnings Concerning Increased Risk of Tendinitis and Tendon Rupture*

The U.S. Food and Drug Administration (FDA) has notified manufacturers of fluoroquinolone antimicrobial drugs that a Boxed Warning in the product labeling concerning the increased risk of tendinitis and tendon rupture is necessary. Through its new authority under the Food and Drug Administration Amendments Act of 2007 (FDAAA), the agency also determined that it is necessary for manufacturers of the drugs to provide a Medication Guide to patients about possible side effects. 

The FDA has notified the manufacturers of these drugs that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to ensure that the benefits of the drug outweigh the risks. The Medication Guide will be considered to be an element of the REMS. The new Boxed Warning and Medication Guide would strengthen warning information already included in product labeling for the fluoroquinolone class of systemic antimicrobial drugs. 

Fluoroquinolones are drugs approved for the treatment or prevention of certain bacterial infections. Like other antibacterial drugs, fluoroquinolones do not treat viral infections such as colds or flu. 

"Fluoroquinolones are effective in treating certain bacterial infections, but health care professionals and patients need to be aware of the increased risk associated with the use of these drugs of developing tendinitis and tendon rupture, particularly for certain patient populations," said Edward Cox, M.D., director, Office of Antimicrobial Products, Center for Drug Evaluation and Research. "The FDA believes it is important to highlight and strengthen information regarding possible side effects of fluoroquinolones because it may affect decisions about the relative risks and benefits associated with these products."

The FDA has conducted a new analysis of the available literature and post-marketing adverse event reports. This new analysisreconfirmsthat use of fluoroquinolones is associated with an increased risk of tendon rupture. It alsodemonstrates that despite the current warning of tendon rupture in the labeling for the fluoroquinolones, large numbers of tendon-related adverse events continue to be reported. The FDA considers this new analysis to be "new safety information" as defined in FDAAA.

The FDA also issued Information for Health Care Professionals today to alert health care professionals to the increased risk of tendinitis and tendon rupture in patients taking these drugs and to highlight new information concerning who may be at higher risk for this side effect. 

The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in people older than 60, in those taking corticosteroid drugs, and in kidney, heart, and lung transplant recipients. Patients experiencing pain, swelling, inflammation of a tendon or tendon rupture should be advised to stop taking their fluoroquinolone medication and to contact their health care professional promptly about changing their antimicrobial therapy. Patients should also avoid exercise and using the affected area at the first sign of tendon pain, swelling, or inflammation.

Manufacturers are being notified of the need to change labeling so that all of the drugs in the class carry uniform updated warning language. These warnings would apply to fluoroquinolones for systemic use (e.g., pills, tablets, capsules and injectable formulations). The warnings would not apply to fluoroquinolones for topical ophthalmic or otic use (e.g., eye and ear drops).

Fluoroquinolone manufacturers are required to submit the safety labeling changes, including the strengthened warnings and the Medication Guide, to the FDA within 30 days, or to provide a reason why they do not believe such labeling changes are necessary. If they do not submit new language, or the FDA disagrees with the new language the company proposes, FDAAA provides strict timelines for resolving the labeling changes and allows the agency to issue an order directing the labeling change as deemed appropriate to address the new safety information. In addition, in accordance with FDAAA, sponsors will be required to assess whether their REMS are achieving the goal of informing patients of the risk of tendon-rupture. These assessments may include a survey of patients' and prescribers' understanding of the risks of tendon-rupture and whether the Medication Guide is being distributed and dispensed with the drug. 

Health care professionals should consider the potential benefits and risks for each patient. While most patients tolerate these medicines well, occasionally some will develop other serious adverse reactions that may include convulsions, hallucinations, depression, abnormalities in heart rhythm, or severe diarrhea. 

The medications involved in this action are: Cipro and generic ciprofloxacin, Cipro XR and Proquin XR (ciprofloxacin extended release), Factive (gemifloxacin), Levaquin (levofloxacin), Avelox (moxifloxacin), Noroxin (norfloxacin), and Floxin and generic ofloxacin.

Information for Healthcare Professionals on Fluoroquinolone Antimicrobial Drugs:
http://www.fda.gov/cder/drug/InfoSheets/HCP/fluoroquinolonesHCP.htm


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## saucywench (Jul 9, 2008)

And here is the (bulk of the) e-mail I sent to my doctor about half an hour ago:

I called in sick yesterday, but was unable to get an appointment with you until next week. The pain and weakness were most severe yesterday; I took four Tylenol 3 over the course of the day, with little to no effect. I am so weary of feeling this way. Although I have been more physically active and stressed of late due to moving my mother in with me, I dont feel that it could be explained away as simply as being out of shape. I have been overactive before but usually manage to rebound after a few days of soreness. This pain and weakness is unrelenting. It feels like a combination of fibromyalgia flare-up and carpal tunnel syndrome flare-up, with the standard backache thrown into the mix. Sleep does not alleviate the aching, stiffness, and soreness.

(1) Fibro symptomsallover body ache; difficulty doing simple, everyday physical tasks
(2) Carpal tunnel syndrome symptomsaching and throbbing of inner arm from wrist to elbow; numbness and tingling of fingers; difficulty in curling fingers to form a fist; inability to or difficulty with grasping objects, e.g., pencil, newspaper, coffee cup, steering wheel
(3) Backachegeneral pain/numbness/swelling at surgery site; stiffness or catch in upper right quadrant of back

Yesterday morning, I began to think of what could possibly be the cause. I have been on this antibiotic, doxycycline, for over a month now. The dermatologist wanted me to take it for an extended period, over the course of the summer. Just as with the three different antibiotics you had prescribed for me, I have seen no evidence that it has helped this folliculitis, if that is indeed the skin condition I am suffering from. The symptoms that I have been experiencing have coincided with the length of time I have been on this antibiotic. I dont know if that is coincidental or not, as it is also about the length of time that I began preparations for my mothers move, but I researched the drug yesterday and found this:
*Doxycycline side effects*
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using doxycycline and call your doctor at once if you have any of these serious side effects: 

severe headache, dizziness, blurred vision;
fever, chills, body aches, flu symptoms;
severe blistering, peeling, and red skin rash;
urinating less than usual or not at all;
pale or yellowed skin, dark colored urine, fever, confusion or weakness;
severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;
loss of appetite, jaundice (yellowing of the skin or eyes); or
easy bruising or bleeding, unusual weakness.
The severe pain in your upper stomach spreading to your back is exactly what I experienced when I first awoke to consciousness yesterday morning. I lay there and distinctly felt a singular, front-to-back sensationa heaviness in my chest that permeated through to my back.

[Insert mention of Tinas post]

I did come in to work today, but I dont know how long I will be able to stay. I only took my first Tylenol 3 about 45 minutes ago (have taken no other medications this morning) and am not feeling any relief.
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I told him that I found it oddly coincidental that I would see a post of this nature (even though my antibiotic is not of the same class as Cipro) on the same day that I am questioning the association of my symptoms with being on the doxycycline.


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## MuleVariationsNYC (Jul 13, 2008)

The association between use of quinolones and tendon rupture has been known about for some time. It's a common question on medical school exams. Mere tendonitis is much more common than rupture, by the way. I'm not sure why the FDA is mandating the warning now, though. I did a quick literature search, and the only new-ish study I saw is one from Spain from earlier this year which puts the rate at about 1% in the highest risk group (heart transplant patients on steroids). If you're not on steroids, and not a transplant recipient, your risk is signifcantly lower than 1%, especially if you're under 60.

Part of me wonders if they're simply trying to cut down on the frequency with which this class of antibiotic is prescribed, by making doctors and patients more nervous about using it. If so, then it's probably a smart move (if a little devious). They're overprescribed as a class, upping the odds of bacteria developing resistance. The way the official statement from the FDA is written seems to suggest that a bit.

As far as why it happens...nobody is completely sure. One research lab has shown that quinolones coincidentally induce production of enzymes that degrade collagen, which is a major component of tendons. This seems like a good candidate theory. By the way, this is different from the how the anti-biotic kills bacteria, which is to disrupt a pair of enzymes necessary for replication of bacterial DNA.


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