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2000
Volume 20, Issue 4
  • ISSN: 1574-8863
  • E-ISSN: 2212-3911

Abstract

Background

Ciprofloxacin is a fluoroquinolone antibiotic widely used in clinical practice with a fluorine atom in its chemical structure. Like other antibiotics, it can induce several adverse effects, such as tendinopathy, musculoskeletal toxicity, peripheral neuropathy, and cardiotoxicity, thereby causing relevant and irreversible health injuries. Ciprofloxacin fluoride's adverse toxicological effect associated with a urinary fluoride concentration above the reference value has not yet been reported.

Objective

This case report aimed to provide evidence of ciprofloxacin treatment intoxication, an antibiotic containing a fluorine atom in its chemical structure, associated with a fluoride urine concentration above the reference value.

Case Presentation

A 32-year-old man developed tendinopathy and peripheral neuropathy on the third day’s night after initiating the ciprofloxacin doses, exhibiting symptoms comparable to a low-power electrical discharge and very intense motor agitation. After following habitual laboratory exams, a urinary fluoride measurement was performed by an ion-selective electrode. The urinary fluoride concentration was above the reference values in mg/g of creatinine.

Conclusion

This is the first study that has described an association among ciprofloxacin-fluoride, tendinopathies, and peripheral neuropathy. The patient's symptomatology has suggested a toxic effect related to fluoride. We consider the documented finding of a fluorine atom at the ciprofloxacin structure and its toxic potential neuropathies and tendinopathies as an issue of alert.

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2025-09-10

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References

  1. DavisR. MarkhamA. BalfourJ.A. Ciprofloxacin.Drugs19965161019107410.2165/00003495‑199651060‑000108736621
     [Google Scholar]
  2. Vance-BryanK. GuayD.R.P. RotschaferJ.C. Clinical pharmacokinetics of ciprofloxacin.Clin. Pharmacokinet.199019643446110.2165/00003088‑199019060‑000032292168
     [Google Scholar]
  3. VidyavathiM. SrividyaG. A review on ciprofloxacin: Dosage form perspective.Int. J. Appl. Pharmac.20180610
     [Google Scholar]
  4. DrugBank. Ciprofloxacin: Uses, Interactions, Mechanism of Action. DrugBank.2022Available from: https://go.drugbank.com/drugs/DB00537
  5. ThaiT. SalisburyB.H. ZitoP.M. Ciprofloxacin.StatPearls2023Available from: https://www.ncbi.nlm.nih.gov/books/NBK535454/
    [Google Scholar]
  6. Campoli-RichardsD.M. MonkJ.P. PriceA. BenfieldP. ToddP.A. WardA. Ciprofloxacin.Drugs198835437344710.2165/00003495‑198835040‑000033292209
     [Google Scholar]
  7. BeggE.J. RobsonR.A. SaundersD.A. GrahamG.G. ButtimoreR.C. NeillA.M. TownG.I. The pharmacokinetics of oral fleroxacin and ciprofloxacin in plasma and sputum during acute and chronic dosing.Br. J. Clin. Pharmacol.2000491323810.1046/j.1365‑2125.2000.00105.x10606835
     [Google Scholar]
  8. dos SantosL. TorrianiM.S. BarrosE. Medicines in clinical pharmacy practice.Artmed201311119
     [Google Scholar]
  9. StrauchmanM. MorningstarM. Fluoroquinolone toxicity symptoms in a patient presenting with low back pain.Clin. Pract.201224e8710.4081/cp.2012.e8724765486
     [Google Scholar]
  10. DukewichM. DaneshA. OnyimaC. GuptaA. Intractable acute pain related to fluoroquinolone-induced peripheral neuropathy.J. Pain Palliat. Care Pharmacother.201731214414710.1080/15360288.2017.130161928358229
     [Google Scholar]
  11. BennettA.C. BennettC.L. WitherspoonB.J. KnopfK.B. An evaluation of reports of ciprofloxacin, levofloxacin, and moxifloxacin-association neuropsychiatric toxicities, long-term disability, and aortic aneurysms/dissections disseminated by the Food and Drug Administration and the European Medicines Agency.Exp. Opin. Drug. Saf.2019181110551063Available from: https://www.tandfonline.com/doi/abs/10.1080/14740338.2019.1665022
    [Google Scholar]
  12. YarringtonM.E. AndersonD.J. Dodds AshleyE. JonesT. DavisA. JohnsonM. LokhnyginaY. SextonD.J. MoehringR.W. Impact of FDA black box warning on fluoroquinolone and alternative antibiotic use in southeastern US hospitals.Infect. Control Hosp. Epidemiol.201940111297130010.1017/ice.2019.24731474240
     [Google Scholar]
  13. KuulaL.S.M. ViljemaaK.M. BackmanJ.T. BlomM. Fluoroquinolone-related adverse events resulting in health service use and costs: A systematic review.PLoS One2019144e021602910.1371/journal.pone.021602931026286
     [Google Scholar]
  14. Al-OmarM.A. Ciprofloxacin: drug metabolism and pharmacokinetic profile.Profiles Drug Subst. Excip. Relat. Methodol.20053120921410.1016/S0099‑5428(04)31006‑322469042
     [Google Scholar]
  15. International Programme on Chemical Safety. Fluorides. World Health Organization.2002Available from: https://apps.who.int/iris/handle/10665/42415
  16. MeierK.H. Fluoride.Poisoning; Drug Overdose, 8e. OlsonK.R. SmollinC.G. AndersonI.B. BenowitzN.L. BlancP.D. Kim-KatzS.Y. New York, NYMcGraw Hill2022Available from: accessmedicine.mhmedical.com/content.aspx?aid=1190445429
    [Google Scholar]
  17. PradhanK.M. AroraN.K. JenaA. SusheelaA.K. BhanM.K. Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth.Acta Paediatr.199584555556010.1111/j.1651‑2227.1995.tb13694.x7633153
     [Google Scholar]
  18. García-MontalvoE.A. Reyes-PérezH. Del RazoL.M. Fluoride exposure impairs glucose tolerance via decreased insulin expression and oxidative stress.Toxicology20092632-3758310.1016/j.tox.2009.06.00819540901
     [Google Scholar]
  19. FDAFDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions | FDA. FDA news release.2018Available from: https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics-risks-mental-health-and-low-blood-sugar-adverse
  20. RusuA MunteanuAC ArbănașiEM UivarosiV Overview of side-effects of antibacterial fluoroquinolones: New drugs versus old drugs, a step forward in the safety profile?Pharmaceutics.2023153804
     [Google Scholar]
  21. MichalakK. Sobolewska-WłodarczykA. WłodarczykM. SobolewskaJ. WoźniakP. SobolewskiB. Treatment of the fluoroquinolone-associated disability: The pathobiochemical implications.Oxid. Med. Cell. Longev.2017201711510.1155/2017/802393529147464
     [Google Scholar]
  22. BidellM.R. LodiseT.P. Fluoroquinolone‐associated tendinopathy: Does levofloxacin pose the greatest risk?Pharmacotherapy201636667969310.1002/phar.176127138564
     [Google Scholar]
  23. RadićJ BralićM KolarM GenorioB PrkićA MitarI. Development of the new fluoride ion-selective electrode modified with fexoy nanoparticles.Molecules202025215213
     [Google Scholar]
  24. Agency for Agency for Toxic Substances and Disease Registry (ATSDR)Toxicological profile for Fluorides, Hydrogen Fluoride, and Fluorine. U.S. Department of Health and Human Services, Public Health Service.2003Available from: https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=212&tid=38
  25. Brasil. Norma Regulamentadora No. 7 (NR-7). Ministério do Trabalho e Previdência.2020Available from: https://www.gov.br/trabalho-e-previdencia/pt-br/composicao/orgaos-especificos/secretaria-de-trabalho/inspecao/seguranca-e-saude-no-trabalho/ctpp-nrs/norma-regulamentadora-no-7-nr-7
  26. StrandL.M. MorleyP.C. CipolleR.J. RamseyR. LamsamG.D. Drug-related problems: their structure and function.DICP199024111093109710.1177/1060028090024011142275235
     [Google Scholar]
  27. PuspitasariA.W. SeruniO.C.L. NadhilahL. Identification of drug-related problems in patients with upper acute respiratory tract infections in Tebet subdistrict health center.Int. J. Appl.Pharmac.2020121697310.22159/ijap.2020.v12s1.FF009
     [Google Scholar]
  28. CipolleR.J. StrandL.M. MorleyP.C. Drug Therapy Problems.Pharmaceutical Care Practice: The Patient-Centered Approach to Medication Management Services, 3e.Chapter 5 CipolleR.J. StrandL.M. MorleyP.C. New York, NYThe McGraw-Hill Companies2012Available from: accesspharmacy.mhmedical.com/content.aspx?aid=56172882
    [Google Scholar]
  29. CipolleR.J. StrandL.M. MorleyP.C. The practice of pharmaceutical care.McGraw-Hill1999Available from: https://books.google.com.br/books?id=XGxuAAAACAAJ
    [Google Scholar]
  30. BaileyR.R. KirkJ.A. PeddieB.A. Norfloxacin-induced rheumatic disease.N. Z. Med. J.1983967365906223241
     [Google Scholar]
  31. GoyalH. DennehyJ. BarkerJ. SinglaU. Achilles is not alone!!! Ciprofloxacin induced tendinopathy of gluteal tendons.QJM2016109427527610.1093/qjmed/hcv20326537954
     [Google Scholar]
  32. TanneJ.H. FDA adds “black box” warning label to fluoroquinolone antibiotics.BMJ2008337jul15 1a81610.1136/bmj.a81618632714
     [Google Scholar]
  33. WilliamsR.J.III AttiaE. WickiewiczT.L. HannafinJ.A. The effect of ciprofloxacin on tendon, paratenon, and capsular fibroblast metabolism.Am. J. Sports Med.200028336436910.1177/0363546500028003140110843129
     [Google Scholar]
  34. StahlmannR. Clinical toxicological aspects of fluoroquinolones.Toxicol. Lett.20021271-326927710.1016/S0378‑4274(01)00509‑412052667
     [Google Scholar]
  35. ShimatsuK. SubramaniamS. SimH. AronowitzP. Ciprofloxacin-induced tendinopathy of the gluteal tendons.J. Gen. Intern. Med.201429111559156210.1007/s11606‑014‑2960‑425047394
     [Google Scholar]
  36. PuckettY. GabbarA. BokhariA.A. Prednisone.StatPearls. StatPearls202216Available from: https://www.ncbi.nlm.nih.gov/books/NBK534809/
    [Google Scholar]
  37. LewisT. CookJ. Fluoroquinolones and tendinopathy: A guide for athletes and sports clinicians and a systematic review of the literature.J. Athl. Train.201449342242710.4085/1062‑6050‑49.2.0924762232
     [Google Scholar]
  38. UsudaK. KonoK. ShimboY. FujiharaM. FujimotoK. KawanoA. KonoR. TsujiH. TanidaE. ImanishiM. FukudaC. SuzukiS. TanakaH. Urinary fluoride reference values determined by a fluoride ion selective electrode.Biol. Trace Elem. Res.20071191273410.1007/s12011‑007‑0044‑617914216
     [Google Scholar]
  39. WHOBiological monitoring of chemical exposure in the workplace: guidelines.1996Available from: https://apps.who.int/iris/handle/10665/41856
  40. WHO,Murray JJ. Appropriate use of fluorides for human health. Geneva1986Available from: https://iris.who.int/handle/10665/39103
  41. Brazil. Ordinance No. 2,914, of December 12, 2011. Ministry of Health.2011Available from: https://bvsms.saude.gov.br/bvs/saudelegis/gm/2011/prt2914_12_12_2011.html
  42. DharV. BhatnagarM. Physiology and toxicity of fluoride.Indian J. Dent. Res.200920335035510.4103/0970‑9290.5737919884722
     [Google Scholar]
  43. MagdalaM. RamosB. SérgioL. ValentimO. Projeto promoção e qualidade de vida-fluoretação das águas de abastecimento público no estado de são paulo life quality promotion project-fluoridation of public supply waters in the state of são paulo.BEPA201291071117
     [Google Scholar]
  44. CesaK. AbeggC. AertsD. Water fluoridation surveillance in brazilian capitals.Epidemiol Serv Saúde, Brasília.201120454755510.5123/S1679‑49742011000400014
     [Google Scholar]
  45. Scientific opinion on dietary reference values for fluoride.EFSA J.2013118333210.2903/j.efsa.2013.3332
     [Google Scholar]
  46. GuthS. HüserS. RothA. DegenG. DielP. EdlundK. EisenbrandG. EngelK.H. EpeB. GruneT. HeinzV. HenleT. HumpfH.U. JägerH. JoostH.G. KullingS.E. LampenA. MallyA. MarchanR. MarkoD. MühleE. NitscheM.A. RöhrdanzE. StadlerR. van ThrielC. ViethsS. VogelR.F. WascherE. WatzlC. NöthlingsU. HengstlerJ.G. Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses.Arch. Toxicol.20209451375141510.1007/s00204‑020‑02725‑232382957
     [Google Scholar]
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Ciprofloxacin’s Structure Causing Fluoride-Related Toxicity: A Case Report
Curr Drug Saf 20, 519 (2025); https://doi.org/10.2174/0115748863321622240819101438
/content/journals/cds/10.2174/0115748863321622240819101438
/content/journals/cds/10.2174/0115748863321622240819101438
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  • Article Type:     Case Report
Keyword(s): case report; Ciprofloxacin fluoride; fluoride toxicity; peripheral neuropathy; tendinopathy; urinary fluoride

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