Safety of oral nifuroxazide – analysis of data from a spontaneous reporting system

Abstract

Nifuroxazide (4-hydroxy-benzoic acid; 2-[(5nitro-2-furanyl)methylene]hydrazide) is a chemotherapeutic agent belonging to the nitrofuran family. Indications for its use are acute and chronic bacterial diarrhea and other diseases with diarrhea (1). The drug has local antibacterial activity against some Gram-positive bacteria of the genus Staphylococcus and Gram-negative bacteria from the Enterobacteriaceae family: Yersinia spp., Escherichia spp., Enterobacter spp., Klebsiella spp. and Salmonella spp. It does not affect the bacteria Proteus vulgaris, Proteus mirabilis and Pseudomonas aeruginosa (1-3). Recently, attention has been paid to its antitumor potential in neuroblastoma, multiple myeloma, colorectal and breast cancer, efficacy in the treatment of graft-versus-host disease and nephroprotection in diabetes (4-10). The exact mechanism of action of nifuroxazide has not yet been identified. It probably has an inhibitory effect on dehydrogenase activity and protein synthesis in bacterial cells. Aldehyde dehydrogenase (ALDH) is responsible for the bioactivation of this prodrug. It has been found that nifuroxazide is a potent inhibitor of the Janus kinase 2 pathways and transcription factor 3 (JAK2/STAT3). It also has direct effects on oxidative stress and apoptosis (2, 4-6). Frequent self-administration of this drug by patients makes it necessary to pay attention to selfmedication, which in accordance with the guidelines of the World Health Organization is defined as ìusing medication by the consumer to treat signs/symptoms or minor health problems, recognized as such by themselvesî. In practice, this term also includes treatment by family members or friends, mainly, when the child is being treated (11). It should be responsible and safe, especially considering that diarrhea, in particular, acute diarrhea, is a serious problem of primary and hospital care. Itís serious complications, such as electrolyte disturbances, oligovolemic shock and even death, are dangerous especially for newborns, babies, small children and elderly people, due to their susceptibility to dehydration (12, 13). The fact that adverse effects inevitably accompany the desired therapeutic effects

Thermodynamics of Intermolecular Interaction Reactions of Biomolecules in Water and Water-Organic Solvents

“…так и грам-отрицательных (Salmonella spp., Klebsiella spp., Enterobacter spp., Escherichia coli, Shigella spp., Proteus spp., Hemophilus influenzae) микроорганизмов. Нифуроксазид малотоксичен, безопасен при пероральном приеме [75] и обладает высокой биодоступностью (>90%) [76]. Однако, его низкая растворимость в воде заставляет исследователей искать более растворимые кристаллические формы нифуроксазида [77].…”

Synthesis, in silico and in vitro studies of hydrazide‐hydrazone imine derivatives as potential cholinesterase inhibitors

“…Isocarboxazid, another hydrazide‐hydrazone derivative, is used in the treatment of depression (Rollas & Küçükgüzel, 2007). Nifuroxazide is used clinically as an anti‐infective (Karłowicz‐Bodalska et al, 2019). The structures of these compounds are given in Figure 2.…”

Does Nifuroxazide Enhance the Effect of Metronidazole Oral Administration in the Treatment of Clostridium difficile Infection?

“…Given that it is absorbed in an insignificant amount; it is impossible to detect it in human urine after oral administration [5]. Thanks to this, systemic side effects rarely occur during its use [6].…”