My lucky day:

Levaquin and Tendonitis, Achilles Tendon ruptures

Jacob Schor ND/FABNO

April 7, 2008

Those of you who I have met in person are well aware that I cannot speak.  At least not very loud.  My voice sounds as if I have laryngitis or a really, really nasty sore throat.  In fact what is actually going on down there is an obscure condition called laryngeal-tracheal amyloidosis.  A mutated plasma cell and its descendents produce antibodies which coalesce into beta-amyloid sheets, somewhat like what occurs in Alzheimer’s disease or mad cow disease.  These clumps of protein thickened my vocal cords preventing them from vibrating and also have altered the tissues of my throat and trachea.

Something about this process has left me more vulnerable to infection, especially pneumonia.  Given the nature of this disease process that is intimately involved with the immune function, the routine immune stimulating strategies, seem to backfire, increasing antibody production and aggravating the problem.  As a result over the years I have on a number of occasions found that antibiotics have been very useful.  Useful as in keeping me alive.  I sometime joke with patients who are fervently against the use of any antibiotic about how much I love them, particularly a rather strong one called Levaquin.  It has probably saved my life on occasion.

I routinely pack a bottle of this drug when traveling.  Experience has taught me that when I get pneumonia, I may progress from feeling fine to extreme debility in a matter of hours.  This is crucial during my ski trips in Canada. Every year since 1999, I have snuck out of the office for a week of ski touring in the Selkirk Mountains of British Columbia. A group of friends and I charter a helicopter which flies us to a remote mountain cabin and leaves us there for a week.

This year I embarked on my adventure with a nasty cold. Fearful that the cold might turn to pneumonia I began taking Levaquin.  I was terrified of getting really sick so far from help.

What I did was dumb.  Dumber than dumb.  By chance a patient mentioned to me today that this particular drug has a particularly nasty side effect.  Levaquin increases the risk of tendonitis to the degree that tendons can rupture.

Early reports of cases appear in a 1992 issue of the Journal of Rheumatology.  Ribard and colleagues in France reported 7 cases of Achilles tendonitis associated with these drugs in which 3 of the patients the Achilles tendon actually ruptured.

Once the association was made between drug and injury other reports quickly followed. In 1996 in Foot Ankle International, doctors from Baylor University in Texas warned that treatment with these drugs,…..should be discontinued at the first sign of tendon inflammation so as to reduce the risk of subsequent rupture.”  

Yet it would seem that this warning went unheeded.  The Scandinavian Journal of Infectious Disease reported five more cases of Achilles tendon problems including 3 full ruptures associated in 2003.  

That same year, the Journal of the American Podiatric Medical Association suggested, “Although the exact mechanism of the relationship is not understood, those who engage in sports or exercise should be advised of the risk of quinolone-induced tendinopathy.”

Even as I was packing my duffle for this most recent trip, a German medical journal reported on a patient who was prescribed a dose a quarter the size of what I routinely take whose Achilles tendon ruptured.

 Bottom line is that these drugs,must therefore be prescribed cautiously and patients must be advised to stop treatment at the slightest warning signs of tendinitis.”  

A warning that I had never heard until a few minutes ago.

Do I feel like a moron or what?  Given that one almost expects tendon injuries in the sort of activity I was engaged in, it is a small wonder that I am alive and well and uninjured today.  I’m feeling lucky.

Currently although citizen groups have petitioned the FDA to do so, there are no black box warnings on Levaquin or associated drugs about this risk.  According to one website, the FDA's database shows 262 reported cases of tendon ruptures, 259 cases of tendonitis, and 274 cases of other tendon disorders. Of these, 61% of the tendon ruptures reported to the FDA were caused by Levaquin.  The related drug Cipro was linked to 23% of the tendon ruptures reported the FDA.

None of the published reports have suggested a mechanism to these injuries and so attempting to prevent them is a guess.  Though feeling fine, I’m going to mix up a bottle of ‘tendon fixer-upper’ herbs tomorrow and take them for a few weeks. 

Though we typically worry about the effect of antibiotics on gut bacteria, it may be we should be putting more attention on these other types of damage.  If antibiotics injure tendons, they probably injure connective tissue.  Considering all the implications in this thought is akin to opening a Pandora’s Box.  Let’s not pursue it further today.

Levaquin so far is the main culprit in this story.  Still there are a number of related drugs that we should apply the same caution to.  They include:

Cipro (Ciprofloxacin)

Penetrex (Enoxacin)

Tequin (Gatifloxacin)

Maxaquin (Lomefloxacin)

Avelox (Moxifloxacin)

Noroxin (Norfloxacin)

Floxin (Ofloxacin)

If you are given any of these drugs, they should be stopped if you develop tendonitis.  Oh, but legally, I can’t suggest that you stop taking any prescription drug.  So instead, as the labels should say (but don’t), ‘Contact your doctor immediately if you have and signs or symptoms of tendon inflammation or injury.’

NOTE:

Speaking of skiing and the potential for injuries, it behooves me to add the link to a 20 second video of a good friend of ours demonstrating how to perform parallel turn on telemark skis.

http://www.youtube.com/watch?v=tO3BBDXL81E

J Rheumatol. 1992 Sep;19(9):1479-81.Links

    Seven Achilles tendinitis including 3 complicated by rupture during fluoroquinolone therapy.

    Ribard P, Audisio F, Kahn MF, De Bandt M, Jorgensen C, Hayem G, Meyer O, Palazzo E.

    Department of Rheumatology, Medical School Xavier-Bichat, Hôpital Bichat, Paris, France.

    We describe 7 Achilles tendinitis occurring during fluoroquinolone treatment. Antibiotic agents used were pefloxacin and ofloxacin. In 3 cases the course was complicated by rupture of the tendon, one of which is histologically documented. The toxic effects of quinolones on tendon is discussed.

Foot Ankle Int. 1996 Aug;17(8):496-8.Links

    Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a case report and literature review.

    McGarvey WC, Singh D, Trevino SG.

    Department of Orthopaedic Surgery, Baylor College of Medicine, Houston, Texas, USA.

    Fluoroquinolone antibiotics (such as olprofloxacin, pefloxacin, ofloxacin, norfloxacin, temafloxacin, etc.) have recently been implicated in the etiology of Achilles tendinitis and subsequent tendon rupture. We report on a patient with bilateral partial Achilles tendon ruptures associated with ciprofloxacin therapy and present a review of the current literature on this increasingly recognized complication. Treatment with fluoroquinolones should be discontinued at the first sign of tendon inflammation so as to reduce the risk of subsequent rupture. Magnetic resonance imaging is useful in distinguishing between Achilles tendinitis and partial tendon rupture.

Scand J Infect Dis. 2003;35(10):768-70.Links

    Levofloxacin-associated Achilles tendon rupture and tendinopathy.

    Melhus A, Apelqvist J, Larsson J, Eneroth M.

    Department of Medical Microbiology, Malmö University Hospital, Malmö, Sweden. asa.melhus@mikrobiol.mas.lu.se

    Fluoroquinolones have a documented ability to induce Achilles tendinopathy. Hitherto, few published reports have implicated levofloxacin. This article reports 5 cases of Achilles tendon disorders, including 3 complicated by rupture of the tendon, during levofloxacin treatment of patients with chronic obstructive pulmonary disease.

J Am Podiatr Med Assoc. 2003 Jul-Aug;93(4):333-5.Click here to read Links

    Fluoroquinolone therapy and Achilles tendon rupture.

    Vanek D, Saxena A, Boggs JM.

    California School of Podiatric Medicine, San Francisco, CA, USA.

    Fluoroquinolones have been associated with tendinopathies. The authors present three cases of Achilles tendinopathy in which the patients' symptoms were preceded by treatment for unrelated bacterial infections with ciprofloxacin. Although the exact mechanism of the relationship is not understood, those who engage in sports or exercise should be advised of the risk of quinolone-induced tendinopathy.

Dtsch Med Wochenschr. 2008 Feb;133(6):241-4.Click here to read Links

    [Fluoroquinolone-induced Achilles tendon rupture]

    [Article in German]

    Maurin N.

    Internist/Nephrologie, Intensivmedizin, Bonn. maurin@t-online.de

    HISTORY AND ADMISSION FINDINGS: A 72-year-old female dialysis patient with insulin-dependent diabetes mellitus who was under long-term medication with oral prednisolone due to chronic obstructive pulmonary disease was given levofloxacin for one week to treat an acute bronchitis (one 500 mg dose on the first day, 125 mg/day orally from second day onwards). One day after the end of levofloxacin treatment, the patient complained about a constant dragging pain above the right heel that receded under local application of diclofenac ointment and inactivity of the right foot. Twelve days after ending administration of levofloxacin, strong pains in the right calf were suddenly felt during normal walking, and active plantar flexion was lost. Palpation showed the right calf to be soft; a distinct gap was found in the middle third of the Achilles tendon. The Thompson test was positive, and the patient was unable to stand on her right toes. INVESTIGATIONS AND DIAGNOSIS: Ultrasonography showed a discontinuity of the right Achilles tendon. A spontaneous Achilles tendon rupture after taking fluoroquinolone was diagnosed. TREATMENT AND COURSE: Conservative treatment was applied due to the reduced general condition. Initial treatment involved a below-knee plaster cast in equinus position; the cast was replaced on the fourth day by a pneumatic walker, which was also worn during mobilisation by physiotherapy. CONCLUSION: A typical feature of fluoroquinolone-induced tendinopathy (FIT) is a considerable latency period in some cases between the commencement of treatment with a fluoroquinolone and the onset of FIT symptoms. In addition to fluoroquinolone intake, there are three other predisposing risk factors for tendinopathy: age over 60 years, long-term treatment with systemic glucocorticoids, and chronic kidney disease. The patient showed a combination of all the aforementioned risk factors. In patients with these risk factors, especially among people with a combination of said risk factors - which is frequently the case with nephrologic and dialysis patients, especially -, fluoroquinolones should be administered only after critical evaluation and with a dosage that is adapted to renal function.

    PMID: 18236349 [PubMed - indexed for ME

Ann Urol (Paris). 1996;30(3):129-30.Links

    [Tendinopathy and fluoroquinolones]

    [Article in French]

    Castagnola C, Suhler A.

    Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard-Herriot, Lyon.

    Tendinopathies, essentially involving the Achilles tendon, which tendon rupture, can be secondary to treatment with fluoroquinolones, and facilitated by corticosteroid therapy, renal failure and sport. Fluoroquinolone treatment must therefore be prescribed cautiously and patients must be advised to stop treatment at the slightest warning signs of tendinitis.