Veterinary Medicine - May 2008 - (Page 258) Histoplasmosis PEER-REVIEWED is not a rst-choice treatment.10 Voriconazole and posaconazole Voriconazole, a triazole structurally related to uconazole,72 and posaconazole, a triazole structurally related to itraconazole, also have activity against H. capsulatum. There are not suf cient data regarding the safety and ef cacy of these newer agents in dogs and cats to warrant recommending their use. They may be considered as rescue therapy for patients in which other treatments have failed. Pharmacokinetic data for these agents in dogs are available.73,74 Amphotericin B In dogs and cats with severe disseminated or pulmonary histoplasmosis, amphotericin B or combination therapy with amphotericin B and itraconazole may provide more effective control.10 Itraconazole treatment is started at the same time as amphotericin B and is continued for the normally recommended duration of treatment (Table 2) after amphotericin B treatment is terminated. Although typically administered intravenously, subcutaneous amphotericin B has been used to treat cryptococcosis.75 Nephrotoxicosis is an important adverse effect of amphotericin B therapy, particularly when the deoxycholate form is used. Since urine changes may precede serum elevations in urea nitrogen and creatinine, serial evaluation of urine speci c gravity and monitoring for evidence of casts, protein, or hematuria should be performed.22 Because of their comparatively reduced nephrotoxicity, the lipid and liposomal forms of amphotericin B are preferred, and should be considered when amphotericin B treatment is indicated.76,77 While the lipid and liposomal forms of amphotericin B are more expensive, this increased expense must be considered in light of increased safety. The nancial and health costs of toxicosis related to using the deoxycholate form may be as much or more of a burden than the additional cost of the lipid forms.78 Supportive therapies Because of the risk of immunosuppression and subsequent dissemination of infection, glucocorticoids are generally TABLE 2 Common Antifungal Treatments for Histoplasmosis in Dogs and Cats* Drug Itraconazole Formulation • Capsules (100 mg) • Oral suspension (10 mg/ml) • Tablets (200 mg) Dosage** Dogs: 10 mg/kg PO every 12 to 24 hours for four to six months† Cats: 5 mg/kg PO every 12 hours for four to six months Dogs: 10–20 mg/kg PO every 12 hours for four to six months Cats: 5–20 mg/kg PO every 12 to 24 hours for at least six months Dogs: 0.25–0.5 mg/kg IV every 48 hours (continue until cumulative dose of 5–10 mg/kg is reached) Cats: 0.10–0.25 mg/kg IV every 48 hours (continue until cumulative dose of 4–8 mg/kg is reached) Dogs: 1 mg/kg IV every 48 hours (continue until cumulative dose of 8–12 mg/kg is reached) Adverse Effects • Anorexia • Vomiting/diarrhea • Hepatotoxicity • Cutaneous vasculitis • Anorexia • Lethargy • Vomiting • Pancytopenia • Hepatotoxicity • Infusion reactions (fever, phlebitis, vomiting, muscle tremors, and anaphylaxis) • Nephrotoxicity (may include inappetence, depression, vomiting, and diarrhea; most likely to occur with amphotericin B deoxycholate) Ketoconazole Amphotericin B†† • Deoxycholate (50 mg/vial) • Abelcet (Enzon Pharmaceuticals) lipid complex (5 mg/ml) * Source: References 8, 10, 22, 38, 44, 50, 80, 81, and 84. ** Each patient must be individually evaluated, and the dosage and duration of treatment must be adjusted according to the patient’s response to therapy. Because bioavailability of the oral suspension is greater than that of the capsules, higher blood concentrations of the drug may result. Carefully monitor patients for toxicosis as noted in the text. † These are common average treatment durations; treatment should continue for about two months after complete resolution of clinical signs. †† Multiple protocols exist for amphotericin B administration. These should be reviewed before beginning treatment with amphotericin B. Consult references 10, 22, and 84 for details. 258 May 2008 VETERINARY MEDICINE
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