Correspondence
More on Fluoroquinolone Antibiotics and Tendon Rupture
N Engl J Med 1995; 332:193January 19, 1995
- Article
To the Editor:
In his letter (Sept. 15 issue),1 Huston described bilateral rupture of the Achilles tendon in a patient treated with enoxacin and prednisone. Although no cases of tendon rupture were reported to the Food and Drug Administration (FDA) during premarketing clinical trials of fluoroquinolones currently on the market, the following information from the FDA's Postmarketing Spontaneous Reporting System does support the need for increased awareness of this adverse event.
As of October 1994, 25 cases of tendon rupture were reported, 22 of them occurring outside the United States. The patients whose ages were reported ranged from 33 to 85 years old; 12 were men and 7 were women. Most of the patients received recommended dosages of fluoroquinolones. However, in seven cases, fluoroquinolone levels could have exceeded the therapeutic ranges because of renal insufficiency, age, or the use of diuretic agents. Seventeen ruptures occurred unilaterally or bilaterally in the Achilles tendon, with the remainder occurring in the shoulder joint or hand. Eleven patients were hospitalized, had surgical repairs, or were disabled for prolonged periods. The ruptures occurred 2 to 42 days after the start of fluoroquinolone therapy. Nine patients had no relevant risk factors for tendon rupture. In the remaining 16, the relevant risk factors included concomitant corticosteroid use in 14, advanced age in 4, and long-term dialysis in 2. One patient, a physician, repeatedly ruptured tendons while playing football.
Currently, the approved product labeling for corticosteroids and ofloxacin lists tendon rupture as a possible adverse event. In addition, there is a warning applicable to this class of drugs that precludes the use of fluoroquinolones in children, adolescents, and pregnant or lactating women. This warning is based on the occurrence of arthropathy in immature animals of various species when fluoroquinolones were administered at doses close to the therapeutic dose in humans. The disruption of the extracellular matrix of cartilage and the depletion of collagen seen in animals suggest that similar degradation may occur in humans with tendon rupture. Further studies are needed to understand the pathogenesis of these lesions.
On the basis of postmarketing reports and published articles,1,2 the FDA will update the labeling for all marketed fluoroquinolones to include a warning about the possibility of tendon rupture. Until further information is available, this will include a recommendation to discontinue treatment with these drugs at the first sign of tendon pain or inflammation and to refrain from exercise until the diagnosis of tendinitis can be confidently excluded. Any serious adverse events suspected to be associated with drug use should be reported to the FDA's MedWatch system (telephone 1-800-FDA-1088).
2 ReferencesAna Szarfman, M.D., Ph.D.
Min Chen, R.Ph., M.S.
Michael D. Blum, M.D.
Food and Drug Administration, Rockville, MD 208571
Huston KA . Achilles tendinitis and tendon rupture due to fluoroquinolone antibiotics. N Engl J Med 1994;331:748-748
Full Text | Web of Science | Medline2
Chaslerie A ,Bannwarth B ,Landreau JM ,Yver L ,Begaud B . Ruptures tendineuses et fluoro-quinolones: un effet indesirable de classe. Rev Rhum Mal Osteoartic 1992;59:297-298
Medline
To the Editor:
Huston's letter reporting a case of tendinitis followed by tendon rupture induced by fluoroquinolone therapy points out that this side effect is little recognized in the United States. In France, this adverse reaction is reported in the Vidal pharmacologic dictionary1 and on the prescribing leaflets of fluoroquinolones.
We have described a series of 100 patients who had tendon disorders, including 31 ruptures, between 1985 and July 1992.2 In our study, the patients (in a 3:1 ratio of men to women) were an average of 63 years old (range, 25 to 84), and many had received steroid therapy.2 The Achilles tendon was affected most often, and half the patients had bilateral tendinitis. However, other tendons can be damaged, such as the long head of the biceps and the long extensor muscle of the thumb. The average time between the start of treatment with the medication and the onset of the symptoms was 13 days, but in a few patients the tendinitis appeared within 1 or 2 days. The course was usually favorable, but a third of patients had persistent symptoms over a period of more than two months.
Huston emphasizes the accuracy of magnetic resonance imaging (MRI) in detecting complete rupture of the Achilles tendon. Our preliminary results confirm that MRI is useful in patients with fluoroquinolone-induced tendinitis and that it allows the early detection and follow-up of any abnormal tendon signal. MRI readily detects thickening of the tendon or changes around the tendon. In addition, signs of degenerative changes or established rupture are also easy to see in T1 and T2 sequences.3 After the withdrawal of the fluoroquinolone, MRI can help to guide treatment, which may include rest, the use of a cane in walking, and even a below-the-knee cast.
Since 1992, practitioners and patients have been informed by the French authorities and pharmaceutical firms of the risk of fluoroquinolone-induced tendinitis as well as of the guidelines to prevent rupture.
3 ReferencesCorinne Pierfitte, M.D.
Pierre Gillet, M.D.
Rene J. Royer, M.D.
Centre Hospitalier Universitaire, 54000 Nancy, France1
Vidal 1994. 70th ed. Paris: OVP-Editions du Vidal, 1994.
2
Royer RJ ,Pierfitte C ,Netter P . Features of tendon disorders with fluoroquinolones. Therapie 1994;49:75-76
Web of Science | Medline3
Gillet P ,Blum A ,Pierfitte C , et al. Fluoroquinolone-associated Achille's tendinitis: MRI findings. Arthritis Rheum 1993;36:Suppl:S163-S163 abstract.
Web of Science
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Umile Giuseppe Longo, Mario Ronga, Nicola Maffulli. (2009) Acute Ruptures of the Achilles Tendon. Sports Medicine and Arthroscopy Review 17:2, 127-138
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