Safety of a pre-formulated amphotericin B lipid emulsion for the treatment of Indian Kala-azar

Amphotericin B (AB) deoxycholate is highly effective in antimony refractory cases for the treatment of visceral leishmaniasis (VL) in Bihar. But the need for prolonged hospitalisation and frequent, occasionally serious, adverse events are its major drawbacks. Lipid formulations of AB are devoid of these problems, but very expensive. We evaluated the safety and efficacy of a commercial standardised amphotericin B emulsion, a product of AB formulated in lipid emulsion vehicle (ABLE) in the treatment of Indian VL. In this open label, non-comparative study, 15 patients in each group were given three daily intravenous infusions each of 3, 4 or 5 mg/kg. All 45 patients (15 in each group) completed the treatment. The drug was tolerated well. Infusion reactions occurred in 5 (11%) patients and vomiting in 2 (4.4%). No nephrotoxicity or other organ toxicity was observed. At the end of treatment all patients of every group were clinically and parasitologically cured. However, during 6 months follow up, three patients from the 5 mg/kg group and one from the 4 mg/kg group tested positive for splenic aspirate. Thus 41 (91.1%; 95% CI 78-97) of 45 patients were cured with a total dose ranging between 9 and 15 mg/kg. There was no dose response linear correlation. In this preliminary study, AB formulated in a lipid emulsion vehicle was safe and effective for the treatment of VL in India.