ANTIFUNGAL THERAPY: PAST, PRESENT, AND FUTURE
ANDREW HANZLICEK, DVM, MS, DACVIM MiraVista Diagnostics, Indianapolis, Indiana
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FDA approved generic itraconazole capsules are essentially equivalent to Sporanox® capsules and provide significant cost-savings. 5, 6 When administration of solution is feasible, Itrafungol® (Elanco, 10 mg/ml) is approved for the treatment of dermatophytosis in cats. It is equivalent to the innovator product (Sporanox®) and can be used off-label for the treatment of IFIs in dogs and cats. FDA approved generic itraconazole solution has an identical ingredient list to Sporanox® solution, but published pharmacokinetic data are not available for dogs or cats. Posaconazole and voriconazole are next generation itraconazole and fluconazole, respectfully. They have an expanded spectrum of activity against molds and are FDA approved for the prevention or treatment of invasive mold or candidiasis in humans. In dogs and cats, posaconazole and voriconazole have been used to treat 5 POSACONAZOLE AND VORICONAZOLE
invasive mold infections including aspergillosis with mixed results. Posaconazole and voriconazole are both effective against Histoplasma, Blastomyces, Coccidioides , and Cryptococcus and can be used as salvage therapy if treatment with itraconazole or fluconazole fails. With FDA approved generic formulations now available, these drugs are now more affordable. Posaconazole is available as a solution (40 mg/ml), which works best for small dogs and cats and as an extended release tablet (100 mg) which can be dosed every other day in dogs (15 kg and larger). Voriconazole is available as a solution (40 mg/ml) that works best for cats and small dogs and tablets (50 mg and 200 mg) that work well for medium-large breed dogs. 6 AMPHOTERICIN B Nephrotoxicity is the dose-limiting property of amphotericin B. Newer lipid or liposomal encapsulated formulations (Abelcet® or Ambisome®) are less nephrotoxic and thus provide
higher tolerable doses. Amphotericin is fungicidal and reaches therapeutic drug concentrations quickly. Maximum blood concentration (Cmax) determines the antifungal activity. As such, it is given IV every other day or 3 days / week (M, W, F). The animal should be well hydrated before amphotericin B administration. Kidney values and blood electrolytes (Na, K, Cl) should be checked before each dose. Cumulative doses of up to 12 mg/kg in cats and 24 mg/kg in dogs are recommended, but lower doses can be beneficial. Once reconstituted, liposomal formulations are good for at least 1 week if refrigerated and drug is removed from the vial aseptically. There is contradictory data regarding the antagonism of amphotericin-b by concurrent administration of an azole. Due to this, and lack of evidence that concurrent administration is beneficial, it is recommended to follow amphotericin with azole (step-down) treatment but not administer the two drugs concurrently.
TABLE 1. Recommended antifungal treatment for select invasive fungal infections in dogs and cats Disease
Mild-Moderate Itra > Flu Itra > Flu Itra = Flu Flu > Itra Posa +/- Terb
Life-threatening Amp-b Amp-b Amp-b Amp-b Amp-b
Salvage Posa > Vori Posa > Vori Posa = Vori Posa = Vori
Blastomycosis Histoplasmosis Coccidioidomycosis Cryptococcosis Aspergillosis (molds)
Itra, itraconazole; Flu, fluconazole; Posa, posaconazole; Vori, voriconazole; Amp-b, lipid or liposomal encapsulated amphotericin b; Terb, terbinafine.
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