An Expert Monograph on Benznidazole (DB11989): Pharmacology, Clinical Efficacy, and Therapeutic Landscape

I. Executive Summary

Benznidazole stands as the first-line and most critical therapeutic agent in the management of Chagas disease, a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. This monograph provides a comprehensive analysis of Benznidazole, synthesizing data from its fundamental chemical properties to its complex clinical applications and the evolving landscape of future research. As a nitroimidazole-class antiprotozoal, Benznidazole functions as a prodrug, requiring reductive activation by a parasite-specific enzyme to exert its cytotoxic effects. This mechanism, primarily involving the depletion of essential parasite thiols, confers a degree of selectivity, yet the drug is associated with a significant and often treatment-limiting toxicity profile.

The clinical efficacy of Benznidazole is dichotomous: it is highly curative in the acute and early chronic stages of infection, particularly in children, but its ability to achieve complete parasitological clearance in long-term chronic disease is limited. Despite this, a growing body of evidence demonstrates its profound clinical benefit in chronically infected adults by slowing the progression of Chagas cardiomyopathy, thus shifting the therapeutic goal from cure to disease modification. However, its utility is hampered by a high incidence of adverse effects, most notably severe dermatological reactions and peripheral neuropathy, which frequently lead to treatment discontinuation.