Description

World Health Organization (WHO)

Furazolidone, a nitrofuran derivative with antibacterial and antiprotozoal activity, was introduced in 1954. In the 1970s it was shown to have a carcinogenic potential following long-term administration to experimental animals. However, the relevance of this to short-term therapy in man has not been established. The risk-benefit assessment varies and furazolidone remains widely available in many countries for the treatment of diarrhoea and enteritis.

Antimicrobial activity

It is active against a wide range of enteric pathogens, including Salmonella enterica, Shigella spp., enterotoxigenic Escherichia coli, Campylobacter jejuni, Aeromonas hydrophila, Plesiomonas shigelloides, Vibrio cholerae and V. parahaemolyticus. Yersinia enterocolitica is intrinsically resistant. Furazolidone is also active against the protozoa Giardia lamblia and Trichomonas vaginalis.

Acquired resistance

Acquired resistance has been observed in V. cholerae O1 and O139, S. enterica serotypes Typhi and Enteritidis, A. hydrophila and Shigella spp. Such resistance may be transferable, and there is cross-resistance with nitrofurantoin. Many of these reports come from the Indian subcontinent, where furazolidone is used widely for treating diarrheal diseases.

Hazard

A questionable carcinogen, use has been restricted.

Pharmaceutical Applications

A non-ionic synthetic compound, available for oral use only. It is poorly soluble in water (40 mg/L) and ethanol (90 mg/L), but dissolves well in dimethylformamide (10 g/L). It decomposes in the presence of alkali.

Contact allergens

Furazolidone belongs to the group of nitrofurans. This antimicrobial (antibacterial and antiprotozoal) agent is used in veterinary medicine both topically and orally, particularly in animal feed. Reactions are reported in workers exposed to it in animal feeds. Cross-reactions with other nitrofuran derivatives are rare.

Biochem/physiol Actions

Furazolidone induces interstrand cross-links in subsequent mutation in bacterial cells. It also inhibits mono and diamine oxidase activities in eukaryotes.

Pharmacokinetics

There is substantial absorption (65–70%) after oral administration, but the drug is heavily metabolized, so that only about 5% of the material excreted is microbiologically active. A dose of 5 mg/kg achieves a maximum plasma concentration of around 1 mg/L. Protein binding is about 30%. Intact drug can be found in various body fluids in concentrations approximating to the minimum inhibitory concentration (MIC) for various intestinal pathogens. Less than 1% of the drug is excreted into urine.

Side effects

Most reported side effects are mild and only rarely cause discontinuation of treatment. Nausea and vomiting are experienced by around 8% of patients. Other adverse events include neurological reactions (mainly headache; 1.3% of patients), ‘systemic’ reactions such as fever and malaise (0.6%) and skin rashes (0.54%). Administration of furazolidone may give rise to inhibition of monoamine oxidase, and disulfiram-like reactions have been reported.

Safety Profile

Poison by ingestion and intraperitoneal routes. Human systemic effects by ingestion: dyspnea, respiratory depression, and eosinophilta. Experimental reproductive effects. Human mutation data reported. Questionable carcinogen. When heated to decomposition it emits toxic fumes of NOx. Furazolidone's use has been restricted or discontinued in many countries, including the United States, due to concerns about potential carcinogenicity and the development of antimicrobial resistance.

Synthesis

Furazolidone, 3-(5-nitrofurfuryliden)amino-2-oxazolidinone (33.7.8), is synthesized from 2-hydroazinoethanol, which is reacted with diethyloxalate to make 3- amino-2-oxazolidone. Reacting this with benzaldehyde gives the corresponding hydrazone (33.3.7). Purifying the resulting product and then reacting it with 5-nitrofurfurol gives furazolidone.

Veterinary Drugs and Treatments

Furazolidone is usually a drug of second choice in small animals to treat enteric infections caused by the organisms listed below. Because it is no longer commercially available (in the USA), it may be difficult to locate.

Definition

ChEBI: A member of the class of oxazolidines that is 1,3-oxazolidin-2-one in which the hydrogen attached to the nitrogen is replaced by an N-{[(5-nitro-2-furyl)methylene]amino} group. It has antibacterial and antiprotozoal properties, and is us d in the treatment of giardiasis and cholera.

Brand name

Benilen;B-fsudi;Carbopuradin;Dapecfuran;Dectolin;Dialidene;Diarexin;Diarin;Diclofur;Doreplston;Dushel;Enterar;Enteroxon;Framenterol;Ft 15;Furaberin;Furacol l.;Furalatin p.;Furalidan;Furaliqua;Furoxona-cp;Fuvitan;Fuxol;Fuzatyl;Galacid;Gamafur s.;Giarlin;Ginvel;Injecur;Intefuran;Kalpec-f;Lacolysat;Mastisept;Multi-med 2;Multi-med 3;Multi-med 6;Neforox alpha cpto;Neftivit;Nicolen r;Nifulin;Parkestress forte;Saleton;Scantrimon;Sibren;Sirben;Syralbuna;Tetrafur;Tranatogen-ova;Ufa-cfo-400;Uterojekt;Vagifurona;Vetoprim;Vsf-medical g 15.

Who Evaluation

Evaluation year: 1993