Amphotericin B: A drug of choice for Visceral Leishmaniasis.

Visceral leishmaniasis or Kala-azar is a vector-borne disease caused by an intracellular parasite of the genus leishmania. In India, Amphotericin B (AmB) is a first-line medication for treating leishmaniasis. After a large-scale resistance to pentavalent antimony therapy developed in Bihar state, it was rediscovered as an effective treatment for Leishmania donovani infection. AmB which binds to the ergosterol of protozoan cells causes a change in membrane integrity resulting in ions leakage, and ultimately leading to cell death. The treatment effect of liposomal AmB can be seen more quickly than deoxycholate AmB because, it has some toxic effects, but liposomal AmB is significantly less toxic. Evidence from studies suggested that ABLC (Abelcet) and ABCD (Amphotec) are as effective as l-AmB but Liposomal form (Ambisome) is a more widely accepted treatment option than conventional ones. Nevertheless, the world needs some way more efficient antileishmanial drugs that are less toxic and less expensive for people living with parasitic infections caused by Leishmania. So, academics, researchers, and sponsors need to focus on finding such drugs. This review provides a summary of the chemical, pharmacokinetic, drug-target interactions, stability, dose efficacy, and many other characteristics of the AmB and their various formulations. We have also highlighted the clinically significant aspects of PKDL and VL co-infection with HIV/TB.

Keratitis occurring in patients treated with miltefosine for post-kala-azar dermal leishmaniasis.

AIM: To describe the characteristic clinical features and management of keratitis in the patients receiving miltefosine for post-kala-azar dermal leishmaniasis (PKDL). METHODS: The medical records of five patients with PKDL who presented with keratitis were reviewed retrospectively from April 2018 to December 2019. The evaluation included a thorough medical history including details on drugs used, particularly miltefosine. The drug causality assessment was also performed. The clinical and microbiological characteristics of keratitis were noted. RESULTS: The ocular symptoms included pain, redness, watering, photophobia and diminution of vision. Slit-lamp biomicroscopy revealed peripheral, paralimbal, ring-shaped, full-thickness stromal infiltration resulting in ulcerative keratitis in all cases. Two patients had unilateral keratitis, while three had bilateral keratitis. All five patients received miltefosine for an average period of 48 days before the onset of keratitis. The corrected distance visual acuity at presentation ranged from hand movement to 20/125. The causality assessment revealed a 'probable' association between the adverse drug reaction and miltefosine in all patients. Discontinuation of miltefosine and initiation of corticosteroid therapy resulted in resolution of keratitis in all cases. The unilateral keratitis treated with topical corticosteroids had improved outcomes, but poor outcomes were found in the bilateral keratitis. CONCLUSION: These observations indicate that prolonged use of miltefosine might cause keratitis that resembles infectious keratitis. Early diagnosis with discontinuation of the drug and initiation of corticosteroid therapy are the key to successful management.

Pharmacovigilance of Miltefosine in Treatment of Visceral Leishmaniasis in Endemic Areas of Bihar, India.

Miltefosine, the only oral drug for visceral leishmaniasis (VL), is being used as the first-line drug under the VL elimination program in the Indian subcontinent. Miltefosine is an oral drug which was used as a topical application for skin metastasis of breast cancer. It was found to be effective against Leishmania donovani The main adverse events (AE) reported previously with miltefosine use includes diarrhea, vomiting, and dehydration. Other AEs include, raised serum alanine transaminase/aspartate aminotransferase and renal parameters such as creatinine. In this study, we report AEs in a large patient cohort of VL treated with miltefosine. The purpose of this pharmacovigilance study was to assess adverse drug reactions (ADRs)/AE of miltefosine treatment under unrestricted condition in the field setup. Patients were followed up to 6 months for therapeutic effectiveness. Outcomes of a larger data set of patients treated with this regimen from April 2012 to March 2015 were recorded. In the present study, 646 patients of VL were given miltefosine. Majority of the study subjects (58%) were male. Relapse occurred in 7% during follow-up period. Main causes of death were VL-pulmonary tuberculosis coinfection, extreme diarrhea, and acute pancreatitis which were reported in 1.7% subjects. Of 553 (85.6%) patients completing full course of treatment, 463 (83.7%) showed ADR with miltefosine during the study period. About 2.3% were suffering severe ADR, 51% from moderate, and the rest had mild ADR. The initial and final cure rate was 97.4% and 85.6%, respectively.

Ambisome plus miltefosine for Indian patients with kala-azar.

The combination of one intravenous administration of 5mg/kg Ambisome and oral administration of miltefosine, 2.5mg/kg/day for 14 days, was evaluated in 135 Indian patients with kala-azar. The Intent-to-Treat cure rate at 6 months was 124 of the 135 enrolled patients (91.9%: 95% CI = 86-96%), and the per protocol cure rate was 124 of 127 evaluable patients (97.6%: 95% CI = 93-100%). Side effects could be attributed to each drug separately: fevers, rigors and back pain due to Ambisome; gastrointestinal side effects due to miltefosine. This combination is attractive for reasons of efficacy, tolerance, and feasibility of administration, although the gastrointestinal side effects of miltefosine require medical vigilance. Clinical Trials.gov identification number: NCT00371995.