Antimicrobial safety: focus on fluoroquinolones.

OBJECTIVE

Infrequent toxicities associated with certain drugs and drug classes have recently gained much attention from different health-care perspectives. To protect the patient, continued surveillance of safety and tolerability data is essential. Data from preclinical testing, phase 1-3 trials, and postmarketing surveillance may be used to objectively assess the risks associated with a specific drug or family of compounds. This review summarizes safety and tolerability data for the quinolones.

RESULTS

The most common adverse events associated with the quinolone class involve the gastrointestinal tract (nausea and diarrhea) and central nervous system (CNS) (headache and dizziness). These adverse events are usually mild and do not require discontinuation of therapy. Uncommon and potentially serious quinolone-related adverse events involve the cardiovascular system (rate-corrected electrocardiographic QT interval prolongation), musculoskeletal system (tendinitis and tendon rupture), endocrine system (glucose homeostasis dysregulation), renal system (crystalluria, interstitial nephritis, and acute renal failure), and the CNS (seizures). Severe idiosyncratic adverse events are specific to individual agents that may share some structural congruity, such as the 1-(2,4)-difluorophenyl group shared by trovafloxacin (associated with hepatitis), temafloxacin (associated with hemolytic-uremic syndrome), and tosufloxacin (associated with eosinophilic pneumonitis). Overall, discontinuation rates from clinical trials were <4% for the currently marketed quinolones. Quinolones with higher discontinuation rates, such as trovafloxacin (7.0%) and grepafloxacin (6.4%), are no longer available for general use.

CONCLUSIONS

The currently marketed quinolones are well tolerated, with safety profiles similar to those of other antimicrobial classes. Although adverse effects are unusual, some, including tendinitis and CNS-related effects, are more common with quinolones than with other antimicrobial classes. Rare adverse effects attributed to some members of the quinolone family (e.g., Torsades de Pointes, hepatotoxicity, and dysglycemias) are more likely to occur in select "susceptible" populations. These adverse events can often be circumvented by avoiding exposure to the specific quinolone. In some cases, the therapeutic value offered by a quinolone may outweigh its potential risks.