Although the exact mechanism of fluoroquinolone-induced retinal degeneration in cats remains to be elucidated, it appears from the literature that a similar retinal degeneration can be reproduced from either direct intravitreal injection of high concentrations of drug or exposure to UVA light and drug in laboratory animals. (19,25) The fluoroquinolone molecular structure is also similar structurally to other drugs that are known to directly induce retinal degeneration, including the cinchona alkaloids and halogenated hydroquinolones. Experimental evidence suggests that both the parent compound and its breakdown products via metabolism and photodegradation are active inducers of retinal degeneration. (18,25) Development of toxicoses also appears to be dependent on the maximum concentration of active drug, metabolite, or both reaching the retina over time. (18) Evaluation of the literature suggests that risk factors predisposing cats to fluoroquinolone-induced retinal degeneration may include the following: 1) large doses or plasma concentrations of drug, 2) rapid IV infusion of the antibiotic, 3) prolonged courses of treatment, and 4) age. Theoretically, other risk factors may also be involved including the following: 1) prolonged exposure to UVA light while the antibiotic is being administered, 2) drug interactions, and 3) drug or metabolite accumulation from altered metabolism or reduced elimination. To date, there are no published reports suggesting that the dose of fluoroquinolones should be reduced in geriatric cats or those with renal or hepatic failure. However, accumulation of fluoroquinolone metabolites in dogs and of the parent compound in humans with decreased renal function has been reported. (8-10) In humans with decreased renal function has been reported. (8-10) humans, fluoroquinolone doses are typically decreased in response to the degree of renal impairment. (28) In general, all fluoroquinolone antibiotics should be reserved for severe or recurrent infections, and whenever possible their use should be based on results whenever possible their use should be based on results of culture and susceptibility tests. When indicated, the fluoroquinolones, including enrofloxacin, can be used with limited risk of developing retinal degeneration in cats, provided the manufacturer's guidelines are adhered to and dose reduction is considered in geriatric cats or those with renal impairment. Dosing on renal impairment. Dosing on exact body weight using split dosing (2.5 mg/kg, PO, q 12 h) and avoidance of rapid IV infusions, and drug interactions may help to reduce the risk of retinal degeneration in some cases. Furthermore, monitoring cats for mydriasis and avoidance of UVA light while undergoing treatment may also be of benefit. Further evaluation of the pharmacokinetics of enrofloxacin and the other fluoroquinolones is required in geriatric cats or those with mild to moderate renal or liver impairment to determine whether drug accumulation, elevated peak concentrations of drug, or both may be occurring in this subset of cats. Therapeutic monitoring of drug concentrations may not always be feasible because of time and cost, but renal panels with dose or frequency reduction in response to the degree of renal impairment and the site and severity of infection may help to reduce retinal toxicosis.
Read full abstract