Tendon Injury and Fluoroquinolone Use: A Systematic Review
Fluoroquinolone antibiotics are commonly used to treat infections and are prescribed by general practitioners, medical specialists and surgeons. Tendon injury has been associated with the use of these medications but the risk associated with newer fluoroquinolones has not been established.
The aim of this systematic review was to evaluate the evidence from observational studies to determine the strength of the association between fluoroquinolone use and tendinopathy, and to identify risk factors for this complication.
We searched MEDLINE, EMBASE and the Cochrane Collaboration from inception through May 2013 to identify observational studies focused on tendon injury and fluoroquinolones. Studies with original data were selected for inclusion following the PRISMA guidelines. Of the 560 abstracts screened, 16 relevant studies were independently rated by three authors (WW, AS, DC) using the Newcastle-Ottawa Quality Assessment Scale, and assigned a quality score out of 9. High-quality studies (i.e. scored 4.5 or higher) are summarized in detail in this article. Data were independently extracted by two authors (WW, AS).
Overall, 16 studies were included in our study. Eight were deemed to be of high quality and five specifically evaluated Achilles tendon rupture. In addition, three studies examined Achilles tendinitis, and three included tendon disorders (including any tendon rupture) as an outcome. Results from these studies suggest that individuals exposed to fluoroquinolones are at increased risk for Achilles tendon rupture, particularly within the first month following exposure to the drug (odds ratios ranged from 1.1 to 7.1). One study showed an increased risk of tendon rupture in those over 60 years of age. Five studies stated that individuals taking fluoroquinolones and oral corticosteroids are at increased risk for tendon injury compared with those taking fluoroquinolones alone. Four studies examined the differential effect of a limited number of fluoroquinolones. Ofloxacin had the highest risk of tendon injury in three of the studies.
Included studies are observational in nature and rely on self-report, which may lead to misclassification or underestimation of tendon injury.
Observational studies showed an increased risk of tendon injury, including tendon rupture and tendinitis, with exposure to fluoroquinolone antibiotic therapy. Although this complication appears to be rare, concomitant corticosteroids increase the risk for tendon injury, which varies depending on the fluoroquinolone used.
KeywordsFluoroquinolones Ofloxacin Levofloxacin Moxifloxacin Norfloxacin
This study was funded by Team Grant OTG-88591 from the Canadian Institutes of Health Research (CIHR). The authors are grateful for the work of Corinne Holubowich and Pamela Richards, Information Specialists at the Health Sciences Library, Li Ka Shing Knowledge Institute, St. Michael’s Hospital and who conducted the literature searches for this review.
Dr. Stephenson had full access to all of the data in the study and takes responsibility for the integrity of the data, the accuracy of the data analysis, and had final responsibility for the decision to submit for publication. Study concept and design, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content was carried out by Drs Stephenson and Rochon, Mr. Wu and Mr. Cortes; acquisition of data was undertaken by Drs Stephenson, Wu and Cortes; statistical analysis was carried out by Drs Stephenson and Wu; funding was obtained by Dr Rochon; and study supervision was carried out by Dr Rochon.
Role of the funding source
The study sponsor did not participate in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the paper for publication.
Conflicts of interest
Drs Stephenson and Rochon, Mr. Wu and Mr. Cortes do not have any conflicts of interest to declare.
- 3.Karistinos A, Paulos LE. “Ciprofloxacin-induced” bilateral rectus femoris tendon rupture. 17(5):406–7.Google Scholar
- 4.Braun D, Petitpain N, Cosserat F, Loeuille D, Bitar S, Gillet P, et al. Rupture of multiple tendons after levofloxacin therapy. Revue du Rhumatisme. 2004;71(6):586–7.Google Scholar
- 6.Mouzopoulos G, Stamatakos M, Vasiliadis G, Skandalakis P. Rupture of adductor longus tendon due to ciprofloxacin. Acta Ortho Belgica. 2005;71(6):743–5.Google Scholar
- 12.O’Donnell DE, Hernandez P, Kaplan A, Aaron S, Bourbeau J, Marciniuk D et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease—2008 update—highlights for primary care. Can Respir J 2008;15(Suppl A):1A–8A.Google Scholar
- 15.Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.Google Scholar
- 17.Wise BL, Peloquin C, Choi H, Lane NE, Zhang Y. Impact of age, sex, obesity, and steroid use on quinolone-associated tendon disorders. Amer J Med. 2012;125(12):1228.e23–8.Google Scholar
- 22.Leone R, Venegoni M, Motola D, Moretti U, Piazzetta V, Cocci A, et al. Adverse drug reactions related to the use of fluoroquinolone antimicrobials: an analysis of spontaneous reports and fluoroquinolone consumption data from three Italian regions. Drug Saf. 2003;26(2):109–20.PubMedCrossRefGoogle Scholar
- 33.Le Huec JC, Schaeverbeke T, Chauveaux, Rivel J, Dehais J, Le Rebeller A. Epicondylitis after treatment with fluoroquinolone antibiotics. J Bone Joint Surg Br. 1995;77(293):295.Google Scholar
- 39.McLauchlan GJ, Handoll HH. Interventions for treating acute and chronic Achilles tendinitis. Cochrane Database Syst Rev 2001;(2):CD000232.Google Scholar