Abstract
Fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin are widely used for the treatment of bacterial infections. Fluoroquinolone-induced adverse effects have not been reported to occur with increased frequency in the elderly, but large trials comparing the tolerability in aged and young individuals are not available. Renal function declines consistently with age and recommendations for dosage changes of renally eliminated fluoroquinolones (ofloxacin, levofloxacin, gatifloxacin) are related to changes in kidney function rather than to age per se. However, during routine clinical work, creatinine clearance data are usually not available; thus it seems more practical to recommend dosage adjustment for elderly individuals in whom low creatinine clearance values can be expected.
Reactions of the gastrointestinal tract are the most often observed adverse effects during therapy with fluoroquinolones; however, compared with many other antibacterials, fluoroquinolones are less frequently associated with diarrhoea. Similarly, hypersensitivity reactions, as observed during therapy with penicillins and other β-lactam agents, occur more rarely during fluoroquinolone therapy. Adverse reactions of the CNS are of particular concern for the elderly population. Elderly patients with impairments of the CNS (e.g. epilepsy, pronounced arteriosclerosis) should be treated with fluoroquinolones only under close supervision. Probably, many signs of possible adverse reactions such as confusion, weakness, loss of appetite, tremor or depression are often mistakenly attributed to old age and remain unreported.
Fluoroquinolones can cause QT interval prolongation. Therefore, they should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalaemia or hypomagnesaemia and patients receiving class IA (e.g. quinidine, procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic agents.
Chondrotoxicity of fluoroquinolones, as observed in immature animals, has led to restricted use in paediatric patients, but there is no indication that similar effects could occur in joint cartilage of adults. Tendinitis and tendon ruptures have occurred in rare cases as late as several months after treatment with some fluoroquinolones. Chronic renal diseases, concomitant use of corticosteroids and age over 60 years have been recognised as risk factors for fluoroquinolone-induced tendon disorders.
Overall, the widely used fluoroquinolones discussed in this review are generally well tolerated. Nevertheless, as with all drugs, their specific adverse effect profiles must be considered when they are chosen for treatment of bacterial infections. Because of physiological changes in renal function and in case of certain comorbidities, some special considerations are necessary when fluoroquinolones are used to treat elderly patients.
Similar content being viewed by others
References
Naber KG, Adam D. Classification of fluoroquinolones. Int J Antimicrob Agents 1998; 10: 255–7
Carbonin P, Pahor M, Bernabei R, et al. Is age an independent risk factor of adverse drug reactions in hospitalized medical patients? J Am Geriatr Soc 1991; 39: 1093–9
Gomolin IH, Siami PF, Reuning-Scherer J, et al., and Oral Suspension Study Group. Efficacy and safety of ciprofloxacin oral suspension versus trimethoprim: sulfamethoxazole oral suspension for treatment of older women with acute urinary tract infection. J Am Geriatr Soc 2001; 49: 1606–13
Hooper DC, Wolfson JS. Adverse effects. In: Hooper DC, Wolfson JS, editors. Quinolone antimicrobial agents. 2nd ed. Washington (DC): American Society for Microbiology, 1993; 489–512
Breen J, Skuba K, Grasela D. Safety and tolerability of gatifloxacin, an advanced-generation, 8-methoxy fluoroquinolone. J Respir Dis 1999; 20 Suppl.: S70–6
Church D, Haverstock D, Andriole VT. Moxifloxacin: a review of its safety profile based on worldwide clinical trials. Today’s Ther Trends 2000; 18: 205–23
Nicolle LE. Quinolones in the aged. Drugs 1999; 58Suppl. 2: 49–51
Stahlmann R, Lode H. Fluoroquinolones. In: Root RK, Waldvogel F, Corey L, et al., editors. Clinical infectious diseases: a practical approach. New York: Oxford University Press, 1999: 305–12
Graber H, Ludwig E, Arr M, et al. Pharmacokinetics of ofloxacin in young and elderly patients [abstract]. Rev Infect Dis 1988; 10Suppl. 1: S106
Chien SC, Chow AT, Natarajan J, et al. Absence of age and gender effects on the pharmacokinetics of a single 500-milligram dose of levofloxacin in healthy subjects. Antimicrob Agents Chemother 1997; 41: 1562–5
Perry CM, Ormrod D, Hurst M, et al. Gatifloxacin: a review of its use in the management of bacterial infections. Drugs 2002; 62(1): 169–207
Tequin™ (gatifloxacin) US Package Insert. Princeton (NJ): Bristol-Myers Squibb Company, 2001
Barman Balfour JA, Lamb HM. Moxifloxacin: a review of its clinical potential in the management of community-acquired respiratory tract infections. Drugs 2000; 59(1): 115–39
Wiseman LR, Balfour JA. Ciprofloxacin: a review of its pharmacological profile and therapeutic use in the elderly. Drugs Aging 1994; 4(2): 145–73
LEVAQUIN [prescribing information]. Raritan (NJ): Ortho-McNeil, 1999
Springsklee M, Reiter C, Meyer JM. Safety and tolerability of moxifloxacin (MXF) [abstract 260]. Antiinfect Drugs Chemother 2000; 17(1): 90
Edlund C, Nord CE. Effect of quinolones on intestinal ecology. Drugs 1999; 58Suppl. 2: 65–70
Edlund C, Beyer G, Hiemer-Bau M, et al. Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora. Scand J Infect Dis 2000; 32: 81–5
Bartlett JG. Clostridium difficile: history of its role as an enteric pathogen and the current state of knowledge about the organism. Clin Infect Dis 1994; 18Suppl. 4: S265–72
Ljungberg B, Nilsson-Ehle I, Edlund C, et al. Influence of ciprofloxacin on the colonic microflora in young and elderly volunteers: no impact of the altered drug absorption. Scand J Infect Dis 1990; 22: 205–8
Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis 1999; 28: 352–64
Bowie WR, Willetts V, Jewesson PJ. Adverse reactions in a dose-ranging study with a new long-acting fluoroquinolone, fleroxacin. Antimicrob Agents Chemother 1989; 33: 1778–82
Lode H. Potential interactions of the extended-spectrum fluroquinolones with the CNS. Drugs Saf 1999; 21: 123–35
Kawahara K, Kawahara M, Goto T, et al. Penetration of sparfloxacin into the human spinal fluid: a comparative study with 5 other fluoroquinolones. Chemotherapy 1991; 39: 149–57
Davey PG, Charter M, Kelly S, et al. Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve. Antimicrob Agents Chemother 1994; 38: 1356–62
Kushner JM, Peckman HJ, Snyder CR. Seizures associated with fluoroquinolones. Ann Pharmacother 2001; 35: 1194–8
Schmuck G, Schürmann A, Schlüter G. Determination of the excitatory potencies of fluoroquinolones in the central nervous system by an in vitro model. Antimicrob Agents Chemother 1998; 42: 1831–6
Dembry LM, Farrington JM, Andriole VT. Fluroquinolone antibiotics: adverse effects and safety profiles. Infect Dis Clin Pract 1999; 8: 421–8
Domagala JM. Structure-activity and structure-side-effect relationship for the quinolone antibacterials. J Antimicrob Chemother 1994; 33: 685–706
Stahlmann R, Lode H. Toxicity of quinolones. Drugs 1999; 58Suppl. 2: 37–42
Takayama S, Hirohashi M, Kato M, et al. Toxicity of quinolone antimicrobial agents. J Toxicol Environ Health 1995; 45: 1–45
Stahlmann R, Schwabe R. Safety profile of grepafloxacin compared with other fluoroquinolones. J Antimicrob Chemother 1997; 40Suppl. A: 83–92
Anderson ME, Mazur A, Yang T, et al. Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics. J Pharmacol Exp Ther 2001; 296(3): 806–10
Kang J, Wang L, Chen XL, et al. Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG. Mol Pharmacol 2001; 59: 122–6
Iannini PB, Kubin R, Reiter C, et al. Reassuring safety profile of moxifloxacin [correspondence]. Clin Infect Dis 2001; 32: 1112–4
Rubinstein E, Camm J. Cardiotoxicity of fluoroquinolones. J Antimicrob Chemother 2002; 49: 593–6
Bertino JS, Owens RC, Carnes TD, et al. Gatifloxacin-associated corrected QT-interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors. Clin Infect Dis 2002; 34: 861–3
Owens RC, Ambrose PG. Torsades de pointes associated with fluoroquinolones. Pharmacotherapy 2002; 22: 663–8
Avelox™ (moxifloxacin hydrochloride) Tablets, US Package Insert. West Haven (CT): Bayer Corporation, 1999
Sherman O, Beizer JL. Possible ciprofloxacin-induced acute cholestatic jaundice. Ann Pharmacother 1994; 28(10): 1162–4
Stahlmann R. Clinical toxicological aspects of fluoroquinolones. Toxicol Lett 2002; 127: 269–77
Grayson SM. Synthetic antibacterial and antiparasitic drugs. In: Kucers ML, TA Crowe, SM Grayson, et al., editors. The use of antibiotics. 5th ed. Oxford: Butterworth, Heinemann, 1997: 981–1060
Lomaestro BM. Fluoroquinolone-induced renal failure. Drug Saf 2000; 22: 479–85
von Keutz E, Christ W. Toxicology and safety pharmacology of quinolones. In: Kuhlmann J, Dalhoff A, Zeiler H-J, editors. Quinolone antibacterials. Handbook of experimental pharmacology, vol 127. Berlin, Heidelberg, New York: Springer-Verlag, 1998: 297–337
Chopra N, Fine PL, Price B, et al. Bilateral hydronephrosis from ciprofloxacin induced crystalluria and stone formation [case report]. J Urology 2000; 164: 438
Förster C, Kociok K, Shakibaei M, et al. Quinolone-induced cartilage lesions are not reversible in rats. Arch Toxicol 1996; 70: 474–81
Förster C, Schwabe R, Lozo E, et al. Quinolone-induced arthropathy: exposure of magnesium-deficient aged rats or immature rats, mineral concentrations in target tissues and pharmacokinetics. Arch Toxicol 1997; 72: 26–32
Lozo E, Riecke K, Schwabe R, et al. Synergistic effect of ofloxacin and magnesium deficiency on joint cartilage in immature rats. Antimicrob Agents Chemother 2002; 46: 1755–9
Stahlmann R, Schwabe R, Pfister K, et al. Supplementation with magnesium and tocopherol diminishes quinoloneinduced chondrotoxicity in immature rats. Drugs 1999; 58Suppl. 2: 393–4
Stahlmann R, Förster C, Shakibaei M, et al. Magnesium deficiency induces joint cartilage lesions in juvenile rats which are identical with quinolone-induced arthropathy. Antimicrob Agents Chemother 1995; 39: 2013–8
Kahn MF, Hayem G. Tendons and fluoroquinolones: unresolved issues. Rev Rhum Engl Ed 1997; 64: 437–9
Pierfitte C, Royer RJ. Tendon disorders with fluoroquinolones. Therapie 1996; 51: 419–20
Van der Linden PD, van de Lei J, Nab HW, et al. Achilles tendinitis associated with fluoroquinolones. Br J Clin Pharmacol 1999; 48: 433–7
Van der Linden PD, van Puijenbroek EP, Feenstra J, et al. Tendon disorders attributed to fluoroquinolones: a study on 42 spontaneous reports in the period 1988 to 1998. Arthritis Rheum 2001; 45: 235–9
Simonin M-A, Gegout-Pottie P, Minn A, et al. Pefloxacininduced Achilles tendon toxicity in rodents: biochemical changes in proteoglycan synthesis and oxidative damage to collagen. Antimicrob Agents Chemother 2000; 44: 867–72
Shakibaei M, Pfister K, Schwabe R, et al. Ultrastructure of Achilles tendons of rats treated with ofloxacin and fed a normal or magnesium-deficient diet. Antimicrob Agents Chemother 2000; 44: 261–6
Shakibaei M, Stahlmann R. Ultrastructure of Achilles tendon from rats after treatment with fleroxacin. Arch Toxicol 2001; 75: 97–102
Shakibaei M, Baumann-Wilschke I, Stahlmann R. Quinolone-induced changes in Achilles tendons from rats persist for several months [abstract]. J Antimicrob Chemother 2001; 47Suppl. S1: 49
Acknowledgements
The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stahlmann, R., Lode, H. Fluoroquinolones in the Elderly. Drugs Aging 20, 289–302 (2003). https://doi.org/10.2165/00002512-200320040-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002512-200320040-00005