Pharmacy World and Science

, Volume 23, Issue 3, pp 89–92 | Cite as

Fluoroquinolone use and the change in incidence of tendon ruptures in the Netherlands

  • P.D. van der Linden
  • B.H.Ch Stricker
  • H.G.M. Leufkens
  • R.M.C. Herings
  • H.W. Nab
  • S. Simonian


Introduction: Shortly after their introduction, fluoroquinolones were associated with reports of tendinitis and tendon rupture. During the past years, the number of reports has risen, possibly because of an increased use of fluoroquinolones. In this study, we describe the use of fluoroquinolones in the Dutch community and the possible public health effects of an association between fluoroquinolone use and tendon ruptures. Methods: In the PHARMO drug database we identified all prescriptions for fluoroquinolones in the period 1991‐1996. The incidence of fluoroquinolone use was expressed as the number of fluoroquinolone episodes per 1000 inhabitants in one year, and extrapolated to the Dutch population after standardisation on age and gender. The annual incidence of non‐traumatic tendon ruptures in the period 1991‐1996 was calculated with data from the nation‐wide hospital registry. The expected number of fluoroquinolone attributable tendon ruptures was calculated on the basis of the use of fluoroquinolones, the number of non‐traumatic tendon ruptures and an assumed relative risk of 1.5‐10. Results: In 1996, approximately 251,000 patients experienced 318,000 episodes of fluoroquinolone use in the Netherlands. Females used more often fluoroquinolones than males, and the number of episodes increased exponentially with age. In the period 1991 through 1996, the absolute number of fluoroquinolone episodes increased by 160%, from 122,000 to 318,000. The absolute number of hospitalised tendon ruptures increased with 28%, from 768 in 1991 to 984 in 1996. Assuming a relative risk of 1.5 to 10.0, 1 to 15 tendon ruptures could be attributed to fluoroquinolone use in 1996. Only 7 % of the observed increase could be attributed to the increased use of fluoroquinolones. If the total increase of hospitalised non‐traumatic tendon ruptures would be attributable to the increase in fluoroquinolone use, this would mean that the risk of non traumatic tendon ruptures to fluoroquinolones would be more than 250 times the risk during non‐use. Conclusion: In the Netherlands, a large simultaneous increase in non‐traumatic tendon ruptures and fluoroquinolone use was observed in the period between 1991 to 1996. Assuming a relative risk of 1.5 to 10.0 for tendon ruptures during fluoroquinolone use, only 0.5 to 7% of the increase in non‐traumatic tendon ruptures could be attributed to the increased fluoroquinolone use. The increase in the incidence of non‐traumatic hospitalised tendon ruptures in the Netherlands is not likely to be explained solely by the increased use of fluoroquinolones.

Adverse drug reactions Ciprofloxacion Correlational study Drug safety Fluoroquinolones Norfloxian Ofloxacin Pharmaco‐epidemiology Population attributable risk (PAR) Tendon ruptures 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med 1991;324(6):384-94.Google Scholar
  2. 2.
    Ball P, Tillotson G. Tolerability of fluoroquinolone antibiotics. Past, present and future. Drug Saf 1995;13(6):343-58.Google Scholar
  3. 3.
    Janknegt R. Fluoroquinolones. Adverse reactions during clinical trials and postmarketing surveillance. Pharm Weekbl Sci 1989;11(4):124-7.Google Scholar
  4. 4.
    Lietman PS. Fluoroquinolone toxicities. An update. Drugs 1995;49(Suppl 2):159-63.Google Scholar
  5. 5.
    Bailey RR, Kirk JA, Peddie BA. Norfloxacin-induced rheumatic disease. N Z Med J 1983;96(736):590.Google Scholar
  6. 6.
    McEwan SR, Davey PG. Ciprofloxacin and tenosynovitis. Lancet 1988;2(8616):900.Google Scholar
  7. 7.
    Franck JL, Bouteiller G, Chagnaud P, Sapene M, Gautier D. Rupture des tendons d'achille chez deux adultes traites par pefloxacine dont un cas bilateral. Rev Rhum Mal Osteoartic 1991;58(12):904.Google Scholar
  8. 8.
    Carrasco JM, Garcia B, Andujar C, Garrote F, de Juana P, Bermejo T. Tendinitis associated with ciprofloxacin. Ann Pharmacother 1997;31(1):120.Google Scholar
  9. 9.
    Huston KA. Achilles tendinitis and tendon rupture due to fluoroquinolone antibiotics. N Engl J Med 1994;331(11):748.Google Scholar
  10. 10.
    McGarvey WC, Singh D, Trevino SG. Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a case report and literature review. Foot Ankle Int 1996;17(8):496-8.Google Scholar
  11. 11.
    Meyboom RH, Olsson S, Knol A, Dekens-Konter JAM, Koning GHP. Achilles tendinitis induced by pefloxacin and other fluoroquinolone derivatives. Pharmacoepidemiology and drug safety 1994;3:185-9.Google Scholar
  12. 12.
    Nightingale SL. From the Food and Drug Administration. Jama 1996;276(10):774.Google Scholar
  13. 13.
    Ribard P, Audisio F, Kahn MF, et al. Seven Achilles tendinitis including 3 complicated by rupture during fluoroquinolone therapy. J Rheumatol 1992;19(9):1479-81.Google Scholar
  14. 14.
    Zabraniecki L, Negrier I, Vergne P, et al. Fluoroquinolone induced tendinopathy: report of 6 cases. J Rheumatol 1996;23(3):516-20.Google Scholar
  15. 15.
    Kahn MF, Hayem G. Tendons and fluoroquinolones. Unresolved issues. Rev Rhum Engl Ed 1997;64(7-9):437-9.Google Scholar
  16. 16.
    Pierfitte C, Royer RJ. Tendon disorders with fluoroquinolones. Therapie 1996;51(4):419-20.Google Scholar
  17. 17.
    Shinohara YT, Tasker SA, Wallace MR, Couch KE, Olson PE. What is the risk of Achilles tendon rupture with ciprofloxacin? J Rheumatol 1997;24(1):238-9.Google Scholar
  18. 18.
    Van der Linden PD, van de Lei J, Nab HW, Knol A, Stricker BHC. Achilles tendinitis associated with fluoroquinolones. Br J Clin Pharmacol 1999;48:433-7.Google Scholar
  19. 19.
    Herings RMC. PHARMO: A record linkage system for postmarketing surveillance of prescription drugs in the Netherlands.: Utrecht University, 1993.Google Scholar
  20. 20).
    Greenland S. Applications of stratified analysis methods. In: Rothman KJ, Greenland S, eds. Modern epidemiology. Philadelphia: Lippincott-Raven Publishers, 1998: 281-300.Google Scholar
  21. 21.
    Davey PG, Bax RP, Newey J, et al. Growth in the use of antibiotics in the community in England and Scotland in 1980-93. BMJ 1996;312:613.Google Scholar
  22. 22.
    Anon. Nordic statistics on medicines 1993-1995. Uppsala: Nordic Council on Medicines, 1996.Google Scholar
  23. 23.
    Natsch S, Hekster YA, Jong R, Heerdink ER, Herings RMC, Meer JWM. Application of the ATC/DDD methodology to monitor antibiotic drug use. Er. J. Clin. Microniol. Infect. Dis. 1998;17:20-24.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • P.D. van der Linden
    • 1
    • 2
  • B.H.Ch Stricker
    • 2
  • H.G.M. Leufkens
    • 1
  • R.M.C. Herings
    • 1
  • H.W. Nab
    • 3
  • S. Simonian
    • 3
  1. 1.Department of Pharmacoepidemiology & Pharmacotherapy, Utrecht Institute for Pharmaceutical SciencesUtrecht Universitythe Netherlands
  2. 2.Department of Epidemiology & BiostatisticsErasmus Medical Centre RotterdamRotterdamthe Netherlands
  3. 3.Dutch Medicines Evaluation BoardThe Haguethe Netherlands

Personalised recommendations