Spironolactone: is it a novel drug for the prevention of amphotericin B-related hypokalemia in cancer patients?

Abstract

Nephrotoxicity is the major adverse effect of amphotericin B (AmB), often limiting administration of full dosage. Selective distal tubular epithelial toxicity seems to be responsible for the profound potassium wasting that is a major clinical side effect of treatment with AmB. Potassium depletion also potentiates the tubular toxicity of AmB. This study was designed to assess the ability of spironolactone to reduce potassium requirements and to prevent hypokalemia in neutropenic patients on AmB treatment. In this study 26 patients with various hematological disorders were randomized to receive either intravenous AmB alone or AmB and oral spironolactone 100 mg twice daily when developing a proven or suspected fungal infection. Patients receiving concomitant AmB and spironolactone had significantly higher plasma potassium levels than those receiving AmB alone (P = 0.0027). Those patients receiving AmB and spironolactone required significantly less potassium supplementation to maintain their plasma potassium within the normal range (P = 0.022). Moreover, urinary potassium losses were significantly less in patients receiving AmB and spironolactone than those receiving AmB alone (P = 0.040). This study showed that spironolactone can reduce potassium requirements and prevent hypokalemia by reducing urinary potassium loss in neutropenic patients on AmB treatment.