Amphotericin B Deoxycholate

Amphotericin B deoxycholate typically is administered as a series of intravenous infusions. Dogs receive 0.5 to 1 mg/kg IV three times weekly to a cumulative dose of 4 to 8 mg/kg or until azotemia develops; cats receive 0.25 mg/kg IV three times weekly to a cumulative dose of 4 to 6 mg/kg. Each dose should be diluted in 5% dextrose and administered to a well-hydrated patient over 10 minutes to 5 hours. Sodium loading and longer infusion times may reduce nephrotoxicity and diminish infusion-related adverse effects, such as trembling, pyrexia, and nausea. Infusion-related adverse effects also may be lessened by pretreatment with diphenhydramine (0.5 mg/kg IV or PO), aspirin (10 mg/kg PO) or other nonsteroidal antiinflammatory drugs, or a physiologic dose of a glucocorticoid. Not all animals experience infusion-related adverse effects, so nonsteroidal antiinflammatory drugs and glucocorticoids should be only administered if such adverse effects are likely based on previous observations. Additionally, tolerance to infusion-related adverse effects often occurs over time, which reduces the need for pretreatment with antiinflammatory drugs. Saline diuresis before administration of amphotericin B may decrease its effect on renal blood flow and should be considered in patients with preexisting renal disease or those at high risk of nephrotoxicity. Other adverse effects reported in humans treated with amphotericin B include hypokalemia, distal renal tubular acidosis, hypomagnesemia, anemia, and nephrogenic diabetes insipidus.

Serum levels of blood urea nitrogen (BUN) and creatinine should be measured before each infusion. If azotemia develops, infusions should be discontinued until it has resolved. Amphotericin B–induced azotemia usually is reversible, but it may take weeks to months for BUN and creatinine levels to return to baseline. Permanent renal damage is more likely to occur in patients with underlying renal disease and in those that are receiving other nephrotoxic drugs concurrently.

A protocol for subcutaneous administration of amphotericin B was developed with the intent of decreasing nephrotoxicity and avoiding the need for prolonged vascular access, and its use for the treatment of cryptococcosis was described by Malik and colleagues (1996) in three dogs and three cats. Amphotericin B deoxycholate (0.5 to 0.8 mg/kg) was diluted in 400 ml (for cats) or 500 ml (for dogs) of 0.45% NaCl/2.5% dextrose and administered subcutaneously two to three times per week to a cumulative dose of 8 to 26 mg/kg. Although this protocol was successful in the six patients described, sterile abscesses caused by local tissue irritation occurred at concentrations higher than 20 mg/L, which is unavoidable in very large dogs. In addition, sterile abscesses often are seen even in smaller dogs for which more dilute concentrations are attainable. Despite this significant adverse affect, this protocol provides an alternative for antifungal therapy when financial limitations preclude the use of triazoles or amphotericin B lipid complex.