Safety and efficacy of allylamines in the treatment of cutaneous and mucocutaneous leishmaniasis: A systematic review

Abstract

Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, and in vitro studies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators—if any—included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80 Leismania tropica infected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing and in vitro studies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, the in vitro synergistic effects of allylamines combined with triazole drugs warrant further exploration.

Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments

“…CL has been largely neglected for drug development because it affects poor people in poor regions of the world [ 100 ]. Most of the current drugs used to treat CL are decades old and have many limitations such significant toxicity and side effects [ 101 ]. Costs are another challenge in low- and middle-income endemic settings, especially with the systemic treatment options.…”

In Vitro study of the leishmanicidal activity of perovskia abrotanoides terpenoid-rich fractions against Leishmania major (MRHO/IR/75/ER)

“…[ 27 ] Among them, allylamines and azoles drug families such as terbinafine which inhibits squalene epoxidase, and ketoconazole that inhibits C14-demethylase (CYP51), are the most interested leishmanicidal agents. [ 28 29 ] drug combination therapy has attracted the researcher's attention to reach a synergic effect on the disease, through herbal medicines. [ 30 ] In this respect, various medicinal plants including families of Fabaceae, Malvaceae, Lythracea, Berberidaceae, Agavaceae, and Asteraceae have been used to treat leishmaniasis by traditional methods.…”

Exploring beyond Common Cell Death Pathways in Oral Cancer: A Systematic Review

“…The risk of bias and methodological quality of the selected studies exploring animal models were independently assessed by applying the Systematic Review Center for Laboratory Animal Experimentation SYRCLE tool [16]. For in vitro studies, the quality of evidence was assessed with the tool developed by the United States national toxicology program, with modifications incorporated by Bezemer et al [17].…”