Amphotericin B Treatment for Indian Visceral Leishmaniasis: Conventional versus Lipid Formulations

Abstract

In Bihar, India, where visceral leishmaniasis is hyperendemic, amphotericin B deoxycholate is now first-line parenteral treatment. To test the efficacy of amphotericin B deoxycholate versus that of its lipid formulations, Indian patients were randomized to receive treatment with amphotericin B deoxycholate (1 mg/kg on alternate days for 30 days; n=51), liposomal amphotericin B (2 mg/kg per day for 5 days; n=51), or amphotericin B lipid complex (2 mg/kg per day for 5 days; n=51). Infusion-associated reactions were frequent and persistent in subjects treated with amphotericin B deoxycholate. The illness of 3 patients failed to respond to treatment, and 5 patients experienced relapse. Final cure rates were similar. Estimated total treatment costs for a 25-kg patient-417 dollars for amphotericin B deoxycholate, 872 dollars for liposomal amphotericin B, and 947 dollars for amphotericin B lipid complex-differed as a result of drug cost. Substantial reductions (approximately 60%) in the price of liposomal amphotericin B and amphotericin B lipid complex would make treatment costs comparable to that of amphotericin B deoxycholate, permitting administration of short-course regimens in India.

Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980–2004

“…AmBisome was reported to produce an average of 0·6 adverse reactions per treatment, compared with 1·4 with Abelcet and 8·4 with amphotericin B deoxycholate. 20 In conclusion, prolonged duration of treatment, need for hospitalisation, and infusion-related adverse events are clear handicaps with amphotericin B deoxycholate (figure 2). Lipid-associated formulations require shorter treatments and are much safer, and toxicity is seldom reported with AmBisome.…”

“…Information provided 12 Sundar et al 13 Thakur et al [14][15][16] Thakur and Narayan 17 Sundar et al 18,20 Amphotericin …”

“…43 Amphotericin B deoxycholate was as active as its liposomal formulations (table 4). Amphotericin B and liposomal amphotericin B (AmBisome, Gilead) had comparable high cure rates at total doses of 20 mg/kg versus 15 mg/kg 34 and 15 mg/kg versus 10 mg/kg, 20 respectively. AmBisome (476 patients in six studies, two of which were comparative, three dose-finding, and one noncomparative; table 5) was associated with high cure rates even at very low doses.…”

“…20,22,23,48,49,50 Efficacy was doserelated in dose-finding studies. Short-course (2 day) regimens were only approximately 80% effective.…”

“…Results indicate that a total dose of at least 10-15 mg/kg should be administered over 5 days to achieve cure rates of 90% or above. 20 Amphotericin B in fat emulsion seems effective but there is too little data to draw conclusions, with only two studies found in the literature. 21,51 Amphotericin B deoxycholate is invariably associated with substantial infusion reactions-eg, fever, chills, and tromboflebitis-and occasionally serious toxicityeg, hypokalaemia, nephrotoxicity, myocarditis, and even death.…”