Safety profile of meglumine antimoniate intralesional infiltration for cutaneous leishmaniasis

ABSTRACT

Objectives: Cutaneous leishmaniasis is a neglected disease, associated with high morbidity, which is partially due to the toxicity of available therapies. The pentavalent antimonial derivatives intralesional infiltration has proven to be as effective as the intravenous drug-based therapy, however, there is a lack of robust safety data.

Methods: Phase II, uncontrolled, unicenter clinical trial to assess the safety profile of a standardized meglumine antimionate intralesional therapy, based on weekly infiltrations.

Results: Fifty-three patients were studied, predominantly men (60%) and young adults (43.7 ± 17.1 years). Overall, 86.9% of the patients had at least one clinical adverse event. Local events were the most frequent (83%), followed by systemic ones (47.3%). Fourteen participants (26%) presented biochemical abnormalities. In all cases, laboratorial alterations were classified as mild and treatment discontinuation was not required. Differently, the two hypersensitivity (3.8%) reactions observed led to permanent treatment interruption. QTc interval prolongation was recorded in 14 patients (25.5%). The following risk associations to adverse events were identified in the multiple analysis: hypertension with systemic clinical events and smoking with QT interval prolongation.

Expert commentary: In general, MA-IL was well tolerated and although associated with local and systemic adverse events, there was a low risk of high intensity or severe complications.

KEYWORDS:

• Cutaneous leishmaniasis
• intralesional infiltration
• antimony
• toxicity
• safety

Article highlights

• Current cutaneous leishmaniasis (CL) treatment is associated with high toxicity;

• Meglumine antimoniate intralesional infiltration (MA-IL) has been recently recommended for localized CL in the Americas, however, scientific evidence about its safety profile is scarce;

• Using a standardized therapeutic protocol, MA-IL was well tolerated, although associated with high frequency of local and mild adverse events, with a low risk of high-intensity or severe complications;

• MA intralesional route has been shown to lead to systemic antimony absorption, confirming the potential to cause systemic toxicity (clinical, biochemical and eletrocardiographic abnormalities) and hypersensitivity reactions;

Smoking is associated with mild and asymptomatic QTc interval increase along MA-IL therapy

Acknowledgments

To the Brazilian Minister of Health for providing the Glucantime® ampoules used in this study.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was funded by CNPq (National Council for Scientific and Technological Development). Project number [405407/206-5].