Safety profile of miltefosine in the treatment of cutaneous leishmaniasis

by Laís Raquel Ribeiro, Sarah Nascimento Silva, Mell Ferreira Saliba, Janaína de Pina Carvalho, Gláucia Cota

Cutaneous leishmaniasis (CL) is a neglected tropical disease that poses a significant public health challenge in Brazil and worldwide. Miltefosine, the only orally administered drug available for CL, was recently incorporated into Brazil’s treatment protocols following recommendations by the World Health Organization (WHO) and revisions by national health authorities. While this represents an important advancement, miltefosine is associated with frequent gastrointestinal side effects and potential teratogenic risks, necessitating careful patient eligibility assessments and close clinical monitoring throughout treatment. Furthermore, the absence of national effectiveness data underscores the need for careful monitoring during large-scale implementation. This study, part of a broader implementation monitoring process, seeks to estimate the frequency, intensity, and seriousness of adverse events (AEs) associated with miltefosine. It also aims to identify factors linked to treatment discontinuation during the pilot phase of miltefosine distribution in the state of Minas Gerais, Brazil. Descriptive analyses were performed to present measures of central tendency and dispersion for the variables. Additionally, a multivariate analysis was conducted to explore relationships between explanatory variables and outcomes of interest. Between 2021 and 2023, 77.1% of patients treated with miltefosine experienced at least one AE. The rate of serious AEs related to treatment was 1.3%. Gastrointestinal symptoms were the most commonly reported AEs, followed by musculoskeletal manifestations. The most frequent laboratory alteration observed was an increase in serum creatinine, which was significantly associated with hypertension, age, and mucosal involvement of leishmaniasis. No pregnancies were recorded during the implementation period. Early treatment discontinuation rate occurred in 11.8% of cases, with discontinuation associated with age and baseline serum creatinine alterations. Half of the patients required temporary treatment interruptions or irregular dosing, extending the treatment duration beyond the planned 28 days. This pharmacovigilance model provides valuable insights, representing an approach potentially applicable to other neglected disease control programs, especially when introducing new treatment technologies.