Elsevier

Clinical Therapeutics

Volume 22, Issue 7, July 2000, Pages 798-817
Clinical Therapeutics

The safety profile of the fluoroquinolones

https://doi.org/10.1016/S0149-2918(00)80053-3Get rights and content

Abstract

Background

Premarketing trials showed the fluoroquinolone agents to have a favorable side-effect profile, with treatment-related adverse events comprising gastrointestinal, central nervous system, and dermatologic effects that were generally mild and reversible on cessation of treatment. However, postmarketing surveillance studies have identified severe adverse events, including severe anaphylaxis, QTc-interval prolongation, and potential cardiotoxicity, associated with 3 quinolone agents that either resulted in the removal of the agent from the market (temafloxacin and grepafloxacin) or significantly restricted its use due to substantial mortality and morbidity associated with liver toxicity (trovafloxacin). To date, there have been no such significant adverse events associated with the older fluoroquinolone agents, including ciprofloxacin, ofloxacin, norfloxacin, and levofloxacin. However, there are fewer data from postmarketing surveillance studies on the most recently approved agents, such as moxifloxacin and gatifloxacin, or agents awaiting approval, such as gemifloxacin.

Objective

This paper examines safety data from the premarketing trials and postmarketing surveillance studies of fluoroquinolones available in the United States.

Methods

A MEDLINE® search was performed to identify all English-language studies published since 1980 concerning the safety profiles of the fluoroquinolones.

Conclusions

The fluoroquinolone antibacterial agents offer broad-spectrum therapy in patients with a variety of infections. Given similar spectra of activity, the choice between quinolones may be based on differences in efficacy and safety or tolerability profiles. Most drug reactions involving these agents are minor and reversible on discontinuing treatment, but adverse effects can be associated with significant mortality and morbidity, as was seen in the case of trovafloxacin and temafloxacin.

References (117)

  • Von RosenstielN et al.

    Quinolone antibacterials. An update of their pharmacology and therapeutic use

    Drugs

    (1994)
  • BlondeauJM

    Expanded activity and utility of the new fluoroquinolones: A review

    Clin Ther.

    (1999)
  • CunhaBA

    The fluoroquinolones for urinary tract infections: A review

    Adv Ther.

    (1994)
  • CunhaBA

    Quinolones: Clinical use and formulary considerations

    Adv Ther.

    (1998)
  • ErnstME et al.

    Levofloxacin and trovafloxacin: The next generation of fluoroquinolones?

    Am J Health Syst Pharm.

    (1997)
  • StrattonC

    Fluoroquinolone antibiotics: Properties of the class and individual agents

    Clin Ther.

    (1992)
  • GuayDR

    The role of the fluoroquinolones

    Pharmacotherapy.

    (1992)
  • FongIW

    The role of fluoroquinolones in the management of skin, soft tissue, and bone infections

    Clin Invest Med.

    (1989)
  • NorrbySR et al.

    Safety and tolerability of fluoroquinolones

    Drugs

    (1993)
  • JustPM

    Overview of the fluoroquinolone antibiotics

    Pharmacotherapy

    (1993)
  • DomagalaJM

    Structure-activity and structure-side-effect relationships for the quinolone antibacterials

    J Antimicrob Chemother.

    (1994)
  • GreenSD

    Indications and restrictions of fluoroquinolone use in children

    Br J Hosp Med.

    (1996)
  • TakizawaT et al.

    The comparative arthropathy of fluoroquinolones in dogs

    Hum Exp Toxicol.

    (1999)
  • KashidaY et al.

    Characterization of fluoroquinolone-induced Achilles tendon toxicity in rats: Comparison of toxicities of 10 fluoroquinolones and effects of antiinflammatory compounds

    Antimicrob Agents Chemother.

    (1997)
  • TakizawaT et al.

    A comparative study of the repeat dose toxicity of grepafloxacin and a number of other fluoroquinolones in rats

    Hum Exp Toxicol.

    (1999)
  • StahlmannR et al.

    Chondrotoxicity and toxicokinetics of sparfloxacin in juvenile rats

    Antimicrob Agents Chemother.

    (1998)
  • KashidaY et al.

    Toxic effects of quinolone antibacterial agents on the musculoskeletal system in juvenile rats

    Toxicol Pathol.

    (1997)
  • US Food and Drug Administration Web site. Public Health Advisory. Trovan (trovafloxacin/alatrofloxacin mesylate). June...
  • Physicians' Desk Reference®

    (2000)
  • WiedemannB et al.

    Mechanisms of quinolone resistance

    Infection

    (1994)
  • PatonJH et al.

    Fluoroquinolone antibiotics. Microbiology, pharmacokinetics and clinical use

    Drugs

    (1988)
  • JorgensenJH et al.

    Activities of newer fluoroquinolones against Streptococcus pneumoniae clinical isolates including those with mutations in the gyrA, parC, and parE loci

    Antimicrob Agents Chemother.

    (1999)
  • BallP et al.

    Tolerability of fluoroquinolone antibiotics. Past, present and future

    Drug Saf.

    (1995)
  • WolfsonJS et al.

    Overview of fluoroquinolone safety

    Am J Med.

    (1991)
  • JanknegtR

    Fluoroquinolones. Adverse reactions during clinical trials and postmarketing surveillance

    Pharm Weekbl Sci.

    (1989)
  • BallP

    Adverse reactions and interactions of fluoroquinolones

    Clin Invest Med.

    (1989)
  • HalkinH

    Adverse effects of the fluoroquinolones

    Rev Infect Dis.

    (1988)
  • ElstonRA et al.

    Possible interaction of ciprofloxacin and cyclosporin A

    J Antimicrob Chemother.

    (1988)
  • VogelLC

    Antibiotic-induced diarrhea

    Orthop Nurs.

    (1995)
  • JacobsNF

    Antibiotic-induced diarrhea and pseudomembranous colitis

    Postgrad Med.

    (1994)
    JacobsNF

    Antibiotic-induced diarrhea and pseudomembranous colitis

    Postgrad Med.

    (1994)
  • BartlettJG

    Clostridium difficile: History of its role as an enteric pathogen and the current state of knowledge about the organism

    Clin Infect Dis.

    (1994)
  • TedescoFJ

    Clindamycin-associated colitis. Review of the clinical spectrum of 47 cases

    Am J Dig Dis.

    (1978)
  • GouldPC et al.

    Antibiotic-associated hemorrhagic colitis

    Am J Gastroenterol.

    (1982)
  • CarbonC et al.

    Pseudomembranous colitis caused by antibiotic therapy. Results of a survey of the patient material from the praxis of 900 gastroenterologists [in French]

    Therapie.

    (1994)
  • StahlmannR et al.

    Chondrotoxicity of ciprofloxacin in immature beagle dogs: Immunohistochemistry, electron microscopy and drug plasma concentrations

    Arch Toxicol.

    (2000)
  • MovinT et al.

    Pathology of the Achilles tendon in association with ciprofloxacin treatment

    Foot Ankle Int.

    (1997)
  • McGarveyWC et al.

    Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: A case report and literature review

    Foot Ankle Int.

    (1996)
  • HarrellRM

    Fluoroquinolone-induced tendinopathy: What do we know?

    South Med J.

    (1999)
  • PierfitteC et al.

    More on fluoroquinolone antibiotics and tendon rupture

    N Engl J Med.

    (1995)
  • SzarfmanA et al.

    More on fluoroquinolone antibiotics and tendon rupture

    N Engl J Med.

    (1995)
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