Safety

The toxicology and safety of Baytril® has been extensively studied in various laboratory animals, as well as in the target species dogs and cats, where it has been proven to be safe and well tolerated. No adverse effects on blood composition or kidney function were observed, nor was it teratogenic or mutagenic. In eukaryotes, Baytril® like other modern fluoroquinolones, has a broad margin of safety because compared to prokaryotes, their enzyme analogue to DNA gyrase is 100–1,000 times less susceptible to "topoisomerase inhibitors". For fluoroquinolones in general, side effects on different organ systems (CNS, gastrointestinal tract, or locomotory system) have been reported. Enrofloxacin has undergone considerable toxicological and safety testing in laboratory species such as mice, rats, and guinea pigs, as well as in the target species dogs and cats (18).

Common to all fluoroquinolones is that they may produce cartilage lesions in weight-bearing joints of growing dogs. Safety studies have shown that puppies between one and four weeks of age tolerated treatment with Baytril® for up to ten days at maximum doses of 25 mg/kg b.w. without showing adverse effects. In young dogs above six weeks of age, however, cartilage was affected depending on the dose and duration of Baytril® administration. By contrast, young cats dosed with Baytril® at maximum doses of 25 mg/kg b.w. for up to 30 days did not develop cartilage lesions. Thus, as a matter of precaution, all growing dogs should be excluded from treatment (25).

Ocular Safety

In 2001, Gelatt et al. reported on ocular side effects in 17 cats treated with enrofloxacin. The major ocular side effects described in this publication are mydriasis, retinal atrophy, attenuated retinal vessels, increased reflectivity of the tapetum, abnormal electroretinogram (ERG) responses, and apparent loss of vision. The study concluded that enrofloxacin-induced retinal degeneration might be a rare and idiosyncratic reaction in some cats (19). A closer evaluation by Wiebe et al. (2002) of the data published by Gelatt et al. revealed that other factors such as dosage and age may also be contributory to the development of retinal degeneration. Sixteen of the 17 cats developing retinal degeneration were overdosed up to six to ten times the recommended dosage of 5 mg/kg. The only cat with vision impairment that was given a normal dose (4.6 mg/kg) was 15 years old (20).

Orbifloxacin and marbofloxacin, other fluoroquinolones approved for use in dogs and cats, have also been reported to cause retinal damage and/or blindness in cats (21). Results of these studies lead to the conclusion that most veterinary approved fluoroquinolones show variable affinity for retinal tissues in cats, while there are marked differences among compounds. In the development phase of pradofloxacin (Veraflox®), a specific study was designed to investigate the effects of this molecule on the feline retina (22). This study clearly demonstrated retinal and ocular safety of pradofloxacin in the cat at doses up to 50 mg/kg, i.e. an at least tenfold safety margin.


References

(18) Altreuther P: Safety and tolerance of enrofloxacin in dogs and cats. Proceedings 1st Int. Symposium on Baytril®: 15-19, 1992
(19) Gelatt KN, van der Woerdt A, Ketring KL, Andrew SE, Brooks DE, Biros BJ, Denis HM, Cutler TJ. Enrofloxacin-associated retinal degeneration in cats. Vet Ophthalmol 2001; 4:99–106.
(20) Wiebe V, Hamilton P. Fluoroquinolone-induced retinal degeneration in cats. JAVMA, 2002; 221(11):1568–1571.
(21) Ramirez CJ, Minch JD, Gay JM, Lahmers SM, Guerra DJ, Haldorson GJ, Schneider T, Mealey KL. Molecular genetic basis for fluoroquinolone-induced retinal degeneration in cats. Pharmacogenet Genomics, 2011; 21:66–75
(22) Messias A, Gekeler F, Wegener A, Dietz K, Kohler K, Zrenner E. Retinal safety of a new fluoroquinolone, pradofloxacin, in cats: assessment with eletroretinography. Doc Ophthalmol 2008; 116:177–191.
(25) Boothe DM: Enrofloxacin revisited. Veterinary Medicine 8: 744-753, 1994.