Adverse effects of ketoconazole in dogs – a retrospective study

Abstract

Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.

The Effect of Ketoconazole on Whole Blood and Skin Ciclosporin Concentrations in Dogs

“…Although a recent retrospective analysis of the adverse effects of KTZ in dogs did not indicate that dose was a factor in the number or severity of adverse effects for KTZ, it has been shown that vomiting occurred more often with co-administration of CSA and KTZ. 7,33 Vomiting in the present study, however, occurred more frequently during Treatment 1. Additionally, inhibition of the CYP 450 enzymes by KTZ has been shown to be dose dependent, which was supported in the present study, with blood and skin CSA concentrations obtained in Treatment 3 being higher than those in Treatment 4.…”

The effect of ketoconazole on whole blood and skin ciclosporin concentrations in dogs

“…Although the margin of safety for CSA administration in canines is much greater than that in humans, adverse effects from CSA have generally been observed to be dose dependent, supporting the importance of using the lowest effective dose. Although a recent retrospective analysis of the adverse effects of KTZ in dogs did not indicate that dose was a factor in the number or severity of adverse effects for KTZ, it has been shown that vomiting occurred more often with co‐administration of CSA and KTZ 7,33 . Vomiting in the present study, however, occurred more frequently during Treatment 1.…”

Treatment of demodicosis in dogs: 2011 clinical practice guidelines

“…When higher daily doses are used then a further increase by 0.1 mg/kg/day is recommended. Other P‐glycoprotein inhibitors, such as ketoconazole or ciclosporin, if given concurrently, increase the likelihood of adverse effects (COE III) 55,56 …”

“…Other P-glycoprotein inhibitors, such as ketoconazole or ciclosporin, if given concurrently, increase the likelihood of adverse effects (COE III). 55,56 More recently, an ABCB1-D1 (MDR-1) mutation considered responsible for the acute toxicity in collie dogs and several other herding breeds has been identified. [57][58][59] Testing for this defect is possible.…”