Fluoroquinolone Adverse Effects and Drug Interactions

Douglas N. Fish, PharmD

Disclosures

Pharmacotherapy. 2001;21(10s) 

In This Article

Carcinogenicity and Teratogenicity

It has long been recognized that fluoroquinolones inhibit mammalian topoisomerase II, the mammalian equivalent of bacterial DNA gyrase.[114] In addition, inhibition of mammalian topoisomerase II results in cytotoxic effects on the target cell.[115] However, concentrations at which fluoroquinolones cause disruption of mammalian DNA are usually 300- to 10,000-fold higher than those required for antibacterial effects.[116] Long-term toxicology studies have found no evidence of carcinogenic effects, and no DNA damage was observed in humans after clinical exposure to the drugs.[117,118]

The teratogenic effects of the fluoroquinolones are highly variable in animal models; harmful fetal effects are apparently specific to dose intensity, animal species, and sometimes route of administration.[14,17,20,23,27,29,38] No teratogenic or embryotoxic effects were associated with high dosages of ciprofloxacin in rats, mice, and rabbits.[14] Levofloxacin in dosages equivalent to 81 times the maximum recommended human dosage (based on body weight) caused decreased fetal body weight and increased fetal mortality in rats, but no teratogenic effects were seen when similar dosages were administered to rabbits.[20] Increased fetal skeletal variations occurred with both oral trovafloxacin and intravenous alatrofloxacin when administered to rats at approximately 4-15 times the highest recommended human dosage (based on body weight); increased perinatal mortality and decreased body weights also were observed with oral administration of these very high dosages.[27] Fetal skeletal variations were not seen when oral trovafloxacin was administered to rabbits at approximately 9 times the highest recommended human dosage (based on body weight). Gatifloxacin produced skeletal malformations, increased late postimplantation fetal loss, and increased neonatal and perinatal mortality when administered to rats in dosages approximately equal to the highest recommended human oral dosage.[29] Administration of moxifloxacin to pregnant rabbits in dosages approximately equal to maximum recommended dosages for humans resulted in decreased fetal body weight and delayed skeletal calcification; fetal birthweights were reduced when moxifloxacin was administered to Cynomolgus monkeys at dosages approximately 2.5 times higher than the maximum dosages recommended in humans.[38]

The fluoroquinolones are classified by the FDA as pregnancy category C agents. No adequate and well-controlled studies have been conducted in pregnant women, and these agents should be used during pregnancy only if the potential benefit outweighs potential risk to the fetus.[14,17,20,23,27,29,38]

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