Furazolidone: History, Mechanism of Action and Adverse Effects

General Description

Furazolidone is a synthetic nitrofuran antimicrobial agent initially used for treating gastrointestinal infections and peptic ulcers before the identification of Helicobacter pylori as a primary cause. It functions by disrupting bacterial metabolism and DNA synthesis through its action as a monoamine oxidase inhibitor. Although resistance rates to furazolidone vary by region, they remain low in China, while some increases have been noted elsewhere. Common adverse effects include nausea, vomiting, and dizziness, with serious effects occurring rarely. Despite concerns over its potential carcinogenicity, no definitive evidence supports this in humans, emphasizing the importance of monitoring and patient education during treatment.

Figure 1. Furazolidone

History

Furazolidone is a synthetic nitrofuran antimicrobial agent that has a significant history in the treatment of gastrointestinal infections and giardiasis. Initially utilized in China for treating peptic ulcers, furazolidone demonstrated effective clinical outcomes before the discovery of Helicobacter pylori as the primary cause of these ulcers. Following this revelation, furazolidone was incorporated into treatment regimens aimed at eradicating H. pylori, particularly as resistance to metronidazole increased. In the 1990s, concerns arose regarding the potential mutagenicity and carcinogenicity of furazolidone, leading to regulatory actions by the United States Food and Drug Administration and the European Medicines Agency, which prohibited its use. Despite these restrictions, furazolidone remains available in several countries, including China, where its use has been modified to address difficult-to-eradicate H. pylori infections. However, recent directives have led to a decline in furazolidone's availability and use in clinical practice. ¹

Mechanism of Action

Furazolidone exhibits its antimicrobial effects through a multifaceted mechanism of action, primarily targeting Helicobacter pylori, a key contributor to gastrointestinal infections. After oral administration, furazolidone achieves high concentrations in the gastrointestinal tract. As a monoamine oxidase inhibitor, furazoidone exhibits strong antioxidative properties, enhancing its therapeutic efficacy. It interferes with bacterial oxidoreductases and inhibits enzymes such as acetyl-coenzyme A, which are essential for bacterial metabolism. This inhibition leads to disruptions in the synthesis of ribosomal proteins and other large molecular proteins, ultimately causing metabolic disorders in bacteria and inflicting DNA damage. Furthermore, furazolidone has been recognized for its additional benefits, including the inhibition of gastric acid secretion and the protection of gastric mucosa, contributing to its longstanding use in treating peptic ulcers. ¹

H. Pylori Resistance to Furazolidone

The effectiveness of furazolidone against H. pylori is notable, with reported resistance rates varying across geographical regions. In China, the rate of H. pylori resistance to furazolidone is relatively low, estimated at around 0% to 4%. However, resistance rates have seen increases in other regions, such as Iran, where resistance jumped from 21.6% to 27.2% in a ten-year span. This contrasts with reports from Asia and South America, showing rates of 23% and 0%, respectively. Interestingly, mutations in the porD and oorD genes of H. pylori have been implicated in the development of resistance to furazolidone. Importantly, furazolidone does not produce cross-resistance with other antibiotics, resulting in a low incidence of secondary drug resistance in treated patients. This unique characteristic, along with its multifaceted action, underscores the importance of monitoring resistance patterns to maintain the efficacy of furazolidone in clinical settings. ¹

Adverse Effects

Furazolidone, a nitrofuran antimicrobial agent, is associated with various adverse effects, although these are generally not significantly higher than those linked to other antibiotic therapies. Common adverse effects of furazolidone include nausea, vomiting, diarrhea, dizziness, headache, drug fever, rash, and orthostatic hypotension. Less frequently, serious conditions such as hemolytic anemia, jaundice, and polyneuritis can occur. The likelihood of adverse effects increases with higher dosages, prolonged treatment durations, and the concurrent use of bismuth. A typical safe daily dose of furazolidone is around 200 milligrams, recommended for a treatment period of 10 to 14 days for effective eradication of Helicobacter pylori. Although concerns regarding the potential carcinogenic effects of furazolidone exist, no definitive evidence confirms such risks in humans. Moreover, furazolidone acts as a monoamine oxidase inhibitor, necessitating avoidance of certain foods and alcohol during treatment to prevent harmful interactions. Regular follow-up and patient education about furazolidone's possible adverse reactions are essential for safe therapy. ²

Reference

1. Han YY, Li JY, Guan JL, Liu M, Li PY. Application of furazolidone in Helicobacter pylori infection eradication. J Dig Dis. 2024; 25(3): 148-155.

2. Mohammadi M, Attaran B, Malekzadeh R, Graham DY. Furazolidone, an Underutilized Drug for H. pylori Eradication: Lessons from Iran. Dig Dis Sci. 2017; 62(8): 1890-1896.