Nifurtimox

Breast Feeding; Lactation; Antiprotozoal Agents; Nitrofurans; Trypanocidal Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

American trypanosomiasis

Warning

H373 (100%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P260, P319, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 24 reports by companies from 1 notifications to the ECHA C&L Inventory.

In multiple prospective controlled trials, nifurtimox therapy was not associated with elevations in aminotransferase or bilirubin levels or with instances of clinically apparent liver injury. Since approval of nifurtimox for American trypanosomiasis, there have been no individual reports of liver injury associated with its use.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Nifurtimox

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

P - Antiparasitic products, insecticides and repellents

QP - Antiparasitic products, insecticides and repellents

P01CC01

Nifurtimox exerts trypanosomal activity against Trypanosoma cruzi, treating Chagas disease. One study reports that nifurtimox and other benzofuran derivatives reduce parasite dehydrogenase activity. Results of a recent phase III clinical trial have shown that a significant number of pediatric patients with acute or chronic Chagas disease treated with nifurtimox were immunoglobulin G (IgG) antibody negative and demonstrated at least a 20% decrease in optical density on two IgG antibody tests for T. cruzi antigens.

The mechanism of action of nifurtimox has not been fully elucidated, however, is believed to occur by the activation of nitroreductase enzymes that produce reactive metabolites with a series of deleterious effects on Trypanosoma cruzi, the parasite causing Chagas disease. The antiprotozoal actions of nifurtimox occur both intracellularly and extracellularly. Inhibition of parasite dehydrogenase activity is another purported mode of action of nifurtimox that warrants further research.

Nifurtimox is largely metabolized via nitroreductase enzymes. Two major inactive metabolites have been identified: M-4 and M-6. The M-4 metabolite is a cysteine conjugate of nifurtimox, while M-6 is likely formed by hydrolytic cleavage of the hydrazone moiety of nifurtimox. Other minor metabolites have also been identified in human plasma.