A Comprehensive Pharmacological and Clinical Monograph on Nifurtimox (DB11820)

Executive Summary

Nifurtimox is a nitrofuran antiprotozoal agent primarily indicated for the treatment of Chagas disease (American Trypanosomiasis) caused by the parasite Trypanosoma cruzi.[1] Developed by Bayer and in medical use since 1965, it recently gained renewed prominence with its accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2020 for use in pediatric patients from birth to less than 18 years of age.[3] It is also a critical component of combination therapy for second-stage Human African Trypanosomiasis (sleeping sickness) caused by

Trypanosoma brucei gambiense.[3]

The mechanism of action of nifurtimox, while not fully elucidated, involves its function as a prodrug that is selectively activated within the parasite. Parasitic nitroreductases convert the drug into a nitro-anion radical, which initiates a redox cycle that generates a cascade of cytotoxic reactive oxygen species (ROS). This overwhelming oxidative stress leads to widespread damage to parasitic DNA, lipids, and proteins, ultimately causing cell death.[3] This same mechanism of DNA damage, however, underpins the drug's most significant safety concerns, including a demonstrated potential for genotoxicity in humans and a theoretical risk of carcinogenicity based on data from structurally related compounds.[6]