Suspected drug eruption in seven dogs during administration of flucytosine

Abstract

7 of 8 dogs receiving combination drug therapy consisting of flucytosine together with amphotericin B and/or a triazole for cryptococcosis or aspergillosis developed cutaneous or mucocutaneous eruptions during the course of treatment. Lesions resolved in all cases following discontinuation of flucytosine despite continued administration of other antifungals, suggesting the eruption was referable primarily to the flucytosine component of therapy. Lesions developed 13 to 41 days (median 20 days) after commencing flucytosine (105 to 188 mg/kg/day divided and given every 8 h; median dose rate 150 mg/kg/day). The cumulative dose of flucytosine given prior to the first signs of the drug eruption ranged from 1.7 to 6.8 g/kg (median 2.3 g/kg). The eruptions consisted of depigmentation, followed by ulceration, exudation and crust formation. The scrotum was affected in all 4 male dogs, the nasal plane in 6 of 7 cases, while the lips, vulva, external ear canal and integument were involved in a smaller number of cases. There was considerable variation in the severity of lesions, with changes being most marked when flucytosine was continued for several days after lesions first appeared. Some dogs experienced malaise and inappetence in association with the suspected drug eruption. Healing took a variable period, typically in excess of 2 weeks after discontinuing flucytosine, with up to 2 months being required for total resolution of the lesions. All lesions resolved eventually without scarring or permanent loss of pigment.

Long‐term outcome of therapy for 59 cats and 11 dogs with cryptococcosis

“…All seven dogs that received 5‐FC developed cutaneous or mucocutaneous drug eruptions within 2 to 8 weeks of commencing treatment. Five of these patients were included in the report which first identified this problem 43 . Because of this side effect, expense and limited availability, 5‐FC is not administered routinely to dogs despite our impression that it is a very effective agent when combined with AMB for preliminary therapy.…”

Antifungal Drug Susceptibility and Phylogenetic Diversity among Cryptococcus Isolates from Dogs and Cats in North America

“…VGII isolates in this study appeared to have higher MICs for most antifungal drugs than the isolates of all other C. gattii molecular types, although the relatively low number of VGII isolates in this study limited our ability to document significance and to compare our results with those of other investigators. Although combination therapy with AMB and FLC or 5FC has been recommended for animals with disseminated disease (1, 8), the use of AMB and 5FC has been limited by expense, and there is a high incidence of cutaneous adverse effects in dogs treated with 5FC (49). High FLC MICs identified in some strains of C. gattii might not correlate with treatment failure in vivo, and clinical breakpoints that define susceptibility versus resistance have not been clearly defined for Cryptococcus spp.…”

Cryptococcosis in domestic animals in Western Australia: a retrospective study from 1995–2006

“…The protracted course of treatment required, involving regular veterinary attention with serological and biochemical monitoring also contributes to the high cost of therapy, and mandates a significant emotional and time commitment from owners [2]. Finally, treatment failure or disease recurrence is not uncommon and may result from stopping therapy prematurely or abandoning therapy due to complications such as nephrotoxicity (amphotericin B) [84], hepatotoxicity (itracon azole) [85], cutaneous drug eruptions (flucytosine) [86], cutaneous vasculitis (itraconazole) and sterile subcutaneous abscesses (amphotericin B) [2,84]. For a variety of reasons, treatment was only attempted in two horses in this series.…”