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FURAZOLIDONE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Furazolidone is a bactericidal agent that appears to act by interfering with bacterial enzyme systems. It is active against E coli, Staphylococci, Salmonella, Shigella, Proteus, Aerobacter aerogenes, Vibrio cholerae, Vibrio parahaemolyticus, Campylobacter jejuni, Yersinia enterocolitica, trichomonads, and Giardia lamblia.
    B) Because of serious adverse reactions after oral administration and possible carcinogenicity, human use has been significantly reduced (DeGroot & Conemans, 1990).

Specific Substances

    1) 3-(5-nitrofurfurylideneamino)-2-oxo-oxazolidine
    2) 2-oxazolidinone, 3-(((5-nitro-2-furanyl)
    3) methylene)amino)-
    4) N-(5-Nitro-2-furfurylidene)amino-2-oxazolidine
    5) 5-nitro-N-(2-oxo-3-oxazolidinyl)-2-
    6) furanmethanimine
    7) Nitrofurazolidone
    8) Nitrofurazolidonum
    9) CAS 67-45-8

Available Forms Sources

    A) FORMS
    1) Furazolidone is available in the United States as a 100 mg tablet and a 50 mg/15 mL liquid (Prod Info, 1988).
    B) USES
    1) Furazolidone is primarily used in humans for the treatment of giardiasis, but has also been used topically for treatment of leg ulcers and vaginal trichomoniasis. It also has extensive use in veterinary medicine and as an animal feed additive (De Groot & Conemans, 1990).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Shortness of breath, pleuritic pain, dizziness, general malaise, headache, vomiting, various rashes, and hypoglycemia have occurred as therapeutic side effects.
    2) Patients with G6PD deficiency are at risk to develop hemolysis. Agranulocytosis has also been rarely reported.
    3) A metabolite of furazolidone is responsible for inhibition of monoamine oxidase. A disulfiram-like reaction is also possible.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Hypertensive crisis is a possibility during a monoamine oxidase reaction, but this has not been reported in humans to date.
    0.2.6) RESPIRATORY
    A) WITH THERAPEUTIC USE
    1) Shortness of breath, pleuritic chest pain, and pulmonary eosinophilia have been seen during therapeutic administration.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Dizziness, drowsiness, headache, and general malaise have been reported with therapeutic use; peripheral neuropathy is rare.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Nausea and vomiting may occur with large therapeutic doses.
    B) WITH POISONING/EXPOSURE
    1) Nausea and vomiting may occur with overdoses.
    0.2.9) HEPATIC
    A) WITH POISONING/EXPOSURE
    1) Biochemical evidence for the potential to cause hepatic damage has been noted in tests, but not reported as an overdose side effect.
    0.2.13) HEMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Patients with G6PD deficiency may experience hemolysis.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Erythema multiforme has been reported as a therapeutic side effect, and may be due to a hypersensitivity reaction. Other rashes have been reported during therapeutic administration or when handled in animal feed.
    0.2.19) IMMUNOLOGIC
    A) WITH THERAPEUTIC USE
    1) Hypersensitivity reactions and serum sickness have been rarely reported with therapeutic use.
    0.2.20) REPRODUCTIVE
    A) Furazolidone is classified as FDA Pregnancy Category C. No reports of congenital defects have been linked to furazolidone therapy.
    B) One gram per kilogram of furazolidone terminated the pregnancy of 5 of 5 mice treated on day 7 of pregnancy, 9 of 10 given the agent on day 1, and 2 of 6 given furazolidone on day 10. Lower birth weights, but no congenital abnormalities were seen in offspring.
    0.2.21) CARCINOGENICITY
    A) Animal studies have indicated that long term use of furazolidone may be tumorigenic. Rats given larger than therapeutic amounts developed mammary tumors.
    0.2.22) OTHER
    A) Disulfiram reactions may occur with use.
    B) This agent is a monoamine oxidase inhibitor.

Laboratory Monitoring

    A) HEMOLYSIS - Patients with G6PD deficiency may experience hemolysis with this agent, and a few patients have experienced agranulocytosis. Patients should be monitored for these conditions.
    B) HYPOGLYCEMIA - Has been reported and blood glucose should be monitored.
    C) EOSINOPHILA - Has been reported with pulmonary complications and eosinophil count and pulmonary function should be monitored.
    D) Monitor liver enzymes in overdose. Hepatic damage has not been seen in humans, but some biochemical evidence has been noted to indicate that hepatic damage may be possible.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) No specific toxic dose has been established. Until more is known, activated charcoal is recommended for overdose.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) Pulmonary eosinophilia and diffuse pulmonary infiltrates due to a hypersensitivity reaction responded within 12 hours to corticosteroid therapy.
    D) Monitor pulse oximetry and/or ABGs, chest x-ray, and pulmonary function tests in symptomatic patients.

Range Of Toxicity

    A) A specific toxic dose has not been established.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Shortness of breath, pleuritic pain, dizziness, general malaise, headache, vomiting, various rashes, and hypoglycemia have occurred as therapeutic side effects.
    2) Patients with G6PD deficiency are at risk to develop hemolysis. Agranulocytosis has also been rarely reported.
    3) A metabolite of furazolidone is responsible for inhibition of monoamine oxidase. A disulfiram-like reaction is also possible.

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypertensive crisis is a possibility during a monoamine oxidase reaction, but this has not been reported in humans to date.
    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypertensive crisis may occur if larger-than recommended doses of furazolidone are given for greater than 5 days consecutively due to its action as a monoamine oxidase inhibitor (USPDI , 2001; Craft et al, 1981).

Respiratory

    3.6.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Shortness of breath, pleuritic chest pain, and pulmonary eosinophilia have been seen during therapeutic administration.
    3.6.2) CLINICAL EFFECTS
    A) DISORDER OF RESPIRATORY SYSTEM
    1) WITH THERAPEUTIC USE
    a) Pulmonary eosinophilia has been reported with furazolidone and may arise from a hypersensitivity reaction (Cortez & Pankey, 1972; Collins & Thomas, 1973).
    b) Shortness of breath and pleuritic chest pain may be followed by diffuse infiltrates and eosinophilia (Cortez & Pankey, 1972).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Dizziness, drowsiness, headache, and general malaise have been reported with therapeutic use; peripheral neuropathy is rare.
    3.7.2) CLINICAL EFFECTS
    A) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) Dizziness, drowsiness, general malaise, and headache have been occasionally seen with therapeutic administration (S Sweetman , 2001; Phillips & Hailey, 1986).
    B) SECONDARY PERIPHERAL NEUROPATHY
    1) WITH THERAPEUTIC USE
    a) Peripheral neuropathy has been rarely reported after therapeutic administration (Manor et al, 1975).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nausea and vomiting may occur with large therapeutic doses.
    B) WITH POISONING/EXPOSURE
    1) Nausea and vomiting may occur with overdoses.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Large therapeutic doses of furazolidone may cause nausea and vomiting (Prod Info, 1988).
    b) Occasionally diarrhea, abdominal pain and bleeding in the intestine have been reported (Wade, 1977; Cohen, 1978).
    2) WITH POIS0NING/EXPOSURE
    a) Overdoses would be expected to cause nausea and vomiting (Prod Info, 1988).

Hepatic

    3.9.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Biochemical evidence for the potential to cause hepatic damage has been noted in tests, but not reported as an overdose side effect.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) WITH POISONING/EXPOSURE
    a) Biochemical evidence for potential hepatic damage was noted by Lowenberg (1970).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL URINE
    1) WITH THERAPEUTIC USE
    a) Darkening of the urine may occur and is due to the presence of furazolidone metabolites (S Sweetman , 2001).

Hematologic

    3.13.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Patients with G6PD deficiency may experience hemolysis.
    3.13.2) CLINICAL EFFECTS
    A) HEMOLYSIS
    1) WITH THERAPEUTIC USE
    a) Patients with a G6PD deficiency are at risk to develop hemolysis (USPDI , 2001) Prod Info, 1988; (Wade, 1977; Cohen, 1978).
    B) AGRANULOCYTOSIS
    1) WITH THERAPEUTIC USE
    a) Agranulocytosis has been reported rarely with therapeutic use of this agent (S Sweetman , 2001).

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Erythema multiforme has been reported as a therapeutic side effect, and may be due to a hypersensitivity reaction. Other rashes have been reported during therapeutic administration or when handled in animal feed.
    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) Contact allergy to furazolidone developed in individuals who hand fed supplements containing this agent (DeGroot & Conemans, 1990; Scharfenberg, 1967; Jirasek & Kalensky, 1975; Laubstein & Niedergesass, 1970).
    2) WITH THERAPEUTIC USE
    a) A vesicular morbilliform pruritic rash has been reported with furazolidone and may be due to a hypersensitivity reaction (Goette & Odom, 1980; Kautz, 1960).
    B) ERYTHEMA MULTIFORME
    1) WITH THERAPEUTIC USE
    a) Erythema multiforme has been reported as a adverse side effect, and may be due to a hypersensitivity reaction (Fisher, 1992)(Altamirano & Bondani, 1989).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPOGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) Hypoglycemia has been reported with furazolidone (Prod Info Furoxone(R), 1996).

Immunologic

    3.19.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypersensitivity reactions and serum sickness have been rarely reported with therapeutic use.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) A reversible hypersensitivity reaction has been observed in a small number of patients who have received furazolidone. The reaction may include hypotension, angioedema, or fever, arthralgia, urticaria, and a vesicular or morbilliform rash (Prod Info Furoxone(R), 1996; Altamirano & Bondani, 1989).
    B) TRANSFUSION REACTION DUE TO SERUM PROTEIN REACTION
    1) WITH THERAPEUTIC USE
    a) Serum sickness was described in two patients who received furazolidone therapeutically in Latin America. It was proposed that the serum sickness was due to yellow dye number 5, which is used in the Latin American tablets, but not US products (Wolfe & Moede, 1978).

Reproductive

    3.20.1) SUMMARY
    A) Furazolidone is classified as FDA Pregnancy Category C. No reports of congenital defects have been linked to furazolidone therapy.
    B) One gram per kilogram of furazolidone terminated the pregnancy of 5 of 5 mice treated on day 7 of pregnancy, 9 of 10 given the agent on day 1, and 2 of 6 given furazolidone on day 10. Lower birth weights, but no congenital abnormalities were seen in offspring.
    3.20.2) TERATOGENICITY
    A) HUMANS
    1) No reports of congenital defects have been linked to furazolidone therapy. Some investigators suggest that furazolidone should be contraindicated during pregnancy because of the potential for agranulocytosis and acute hemolysis in individuals with G6PD deficiency (Chow & Jewesson, 1985).
    B) ANIMAL STUDIES
    1) MICE - One gram per kilogram of furazolidone terminated the pregnancy of 5 of 5 mice treated on day 7 of pregnancy, 9 of 10 given the agent on day 1, and 2 of 6 given furazolidone on day 10. Lower birth weights, but no congenital abnormalities were seen in offspring (Jackson & Robson, 1957).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Furazolidone is classified as FDA Pregnancy Category C (Prod Info Furoxone(R), 1999).
    3.20.5) FERTILITY
    A) SEMEN ABNORMAL
    1) When 100 milligrams per kilogram was administered to rats for 7 days, atrophy and degeneration of the seminiferous tubules occurred (Miyaji et al, 1964).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Animal studies have indicated that long term use of furazolidone may be tumorigenic. Rats given larger than therapeutic amounts developed mammary tumors.
    3.21.3) HUMAN STUDIES
    A) ANIMAL STUDIES
    1) Animal studies have indicated that long term use of furazolidone may be tumorigenic (Anon, 1983). Rats given larger than therapeutic amounts developed mammary tumors (Anon, 1984)

Genotoxicity

    A) Furazolidone has been shown to have mutagenic activity in several strains of Salmonella typhimurium (Ni et al, 1987), in Drosophilia melanogaster (Kramers, 1982) Blijleven et al, 1977), in Bacillus subtilis (Ohta et al, 1980), and in Escherichia coli (Ebringer & Bencova, 1980).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) HEMOLYSIS - Patients with G6PD deficiency may experience hemolysis with this agent, and a few patients have experienced agranulocytosis. Patients should be monitored for these conditions.
    B) HYPOGLYCEMIA - Has been reported and blood glucose should be monitored.
    C) EOSINOPHILA - Has been reported with pulmonary complications and eosinophil count and pulmonary function should be monitored.
    D) Monitor liver enzymes in overdose. Hepatic damage has not been seen in humans, but some biochemical evidence has been noted to indicate that hepatic damage may be possible.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) Patients with G6PD deficiency may experience hemolysis with this agent, and a few patients have experienced agranulocytosis. Patients should be monitored for these
    2) EOSINOPHILA has been reported with pulmonary complications. Eosinophil count should be monitored.
    B) BLOOD/SERUM CHEMISTRY
    1) HYPOGLYCEMIA has been reported. Blood glucose should be monitored.
    2) MONITOR LIVER ENZYMES in overdose. Hepatic damage has not been seen in humans, but some biochemical evidence has been noted to indicate that hepatic damage may be possible.
    4.1.3) URINE
    A) URINALYSIS
    1) COLOR - Furazolidone may produce rust-yellow to brown colored urine (Knoben & Anderson, 1988).

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Several methods for analysis are available, the most popular being ultraviolet spectrometry, high performance liquid chromatography with ultraviolet spectrometry, or high performance thin-layer chromatography with spectrometric determination (Elsayed et al, 1980) Smalidge et al, 1981; (Cieri, 1978; Rauter, 1979).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) HEMOLYSIS - Patients with G6PD deficiency may experience hemolysis with this agent, and a few patients have experienced agranulocytosis. Patients should be monitored for these conditions.
    B) HYPOGLYCEMIA - Has been reported and blood glucose should be monitored.
    C) EOSINOPHILA - Has been reported with pulmonary complications and eosinophil count and pulmonary function should be monitored.
    D) Monitor liver enzymes in overdose. Hepatic damage has not been seen in humans, but some biochemical evidence has been noted to indicate that hepatic damage may be possible.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) OBSERVATION REGIMES
    1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    2) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    B) MONITORING OF PATIENT
    1) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.
    2) This agent may cause hepatotoxicity. Monitor liver function tests in patients with significant exposure.
    3) Monitor pulse oximetry and/or ABGs, chest x-ray, and pulmonary function tests in symptomatic patients.
    C) ASTHMATIC PULMONARY EOSINOPHILIA
    1) Diffuse pulmonary infiltrates and pulmonary eosinophilia due to a hypersensitivity reaction responded, within 12 hours, to corticosteroid therapy (200 milligram bolus and then 40 mg daily).
    2) Prior to the use of corticosteroids, bronchodilators, antibiotics, expectorants, supportive measures, and inhalation therapy had been used with little success (Cortez & Pankey, 1972a).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) A specific toxic dose has not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) The usual adult dose is 100 milligrams four times daily for 7 to 10 days (AMA, 1986) Prod Info, 1988).
    7.2.2) PEDIATRIC
    A) ROUTE OF ADMINISTRATION
    1) ORAL (LIQUID OR TABLET)
    a) CHOLERA
    1) The recommended oral dose for treating cholera or diarrhea produced by susceptible bacterial organisms in children 1 month of age and older is 1.25 milligrams per kilogram of body weight four times daily for 5 to 7 days (USPDI, 1995).
    b) GIARDIASIS
    1) The recommended oral dose for treatment of giardiasis in children 5 years or older is 7.5 to 15 milliliters four times daily for 7 to 10 days; for children 1 to 4 years of age 5 to 7.5 milliliters four times daily for 7 to 10 days; for children less than 1 year of age 2.5 to 5 milliliters four times daily for 7 to 10 days. Use in infants under 1 month is not recommended. Dosage is based on weight; 1.25 to 2 milligrams/kilogram/dose four times daily (Prod Info Furoxone(R), 1996; Anon, 1991; USPDI, 1995).
    2) The maximum recommended oral dose for children is 8.8 milligrams/kilogram/day. Dosing exceeding 8.8 milligrams/kilogram/day may produce nausea or vomiting (Prod Info Furoxone(R), 1996; USPDI, 1995).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) PEDIATRIC
    1) The maximum recommended oral dose for children is 8.8 milligrams/kilogram/day (Prod Info, 1988).
    2) The maximum tolerated human exposure to this agent has not been delineated.
    B) ANIMAL DATA
    1) CHRONIC
    a) When 100 milligrams per kilogram was administered to rats for 7 days, atrophy and degeneration of the seminiferous tubules was seen (Miyaji et al, 1964).
    b) Rats given 0.03, 0.1, or 0.3 percent furazolidone in their diet for 35 days developed central nervous system symptoms and changes in spermantogenesis (Rogers et al, 1956).
    c) Dogs given 7.5 or 25 milligrams per kilogram for up to six months developed central nervous system symptoms and changes in spermatogenesis (Rogers et al, 1956).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 300 mg/kg (RTECS, 2001)
    B) LD50- (ORAL)MOUSE:
    1) 4.5 g/kg (Rogers et al, 1956)
    2) 1782 mg/kg (RTECS, 2001)
    C) LD50- (ORAL)RAT:
    1) 2.3 g/kg (Goldenthal, 1971)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Furazolidone interferes with several bacterial enzyme systems resulting in bactericidal effects.
    1) Furazolidone is active against E coli, Staphylococci, Salmonella, Shigella, Proteus, Aerobacter aerogenes, Vibrio cholerae, Vibrio parahaemolyticus, Campylobacter jejuni, Yersinia enterocolitica, trichomonads, and Giardia lamblia (S Sweetman , 2001) Prod Info, 1988; (Phillips & Hailey, 1986).
    B) Furazolidone has monoamine oxidase inhibitor activity which is related to its metabolites and not the parent compound (Palm et al, 1967; AMA, 1986). It is an irreversible inhibitor (Palm et al, 1967).

Physicochemical

Physical Characteristics

    A) yellow crystals

Molecular Weight

    A) 225.2

Animal Toxicology

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) CHICKENS - When furazolidone was tested on heart preparations in chickens, detrimental changes in myocardial vascular resistance and lactate dehydrogenase release was noted at concentrations only moderately above the therapeutic level (McCallum et al, 1989).
    B) DUCKS - Furazolidone has been shown to induce congestive cardiomyopathy and ascites in ducks. The severity increased with the concentration of furazolidone. Other symptoms of furazolidone toxicosis included growth retardation, hydropericardium, and biventricular dilatation (Van Vleet & Ferrans, 1983).
    C) TURKEYS - Furazolidone produces primary hepatic damage that is reflected in total serum proteins being reduced, including trypsin inhibitory capacity (Staley et al, 1978). Cardiac dilatation and myopathy has been seen in turkeys (Jankus et al, 1972; Czarnecki & Grahn, 1980).
    D) THIAMINE - Furazolidone is known to antagonize the utilization of thiamine in poultry (Ali & Bartlet, 1982).
    11.1.2) BOVINE/CATTLE
    A) Increased erythrocytes and hemoglobin concentration were noted in calves treated with furazolidone (Khomenko, 1966). Anorexia, weight loss, nervous signs, and death have been reported in calves given furazolidone (Hoyashi, 1976; Pietsch, 1978).
    11.1.4) CAPRINE/GOAT
    A) CASE HISTORY - Goats given daily doses of 160 mg/kg or greater of furazolidone became anemic, anorexic, hyperexcitable, uneasy, and developed locomotor difficulties such as walking backward and circling (Ali et al, 1984).
    1) Animals died within 5 to 7 days. Necropsy showed mild edema of the brain and fatty changes in the brain and adrenals. Hepatic and renal damage was found on biochemical examination (Ali et al, 1984).
    B) Similar, but less extensive changes were seen at lower doses. Toxicity resembled those of thiamine deficiency in ruminants (Ali et al, 1984).

Treatment

    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.5) TREATMENT
    A) GOAT
    1) Toxicity resembled thiamine deficiency, so thiamine 100 mg/animal was injected daily to goats receiving 320 mg per day of furazolodine (a fatal dose within 5 to 7 days).
    a) The thiamine ameliorated, but did not eliminate, the toxicity of furazolidone. The positive effect was most evident on the neurologic symptoms (Ali et al, 1984).

References

General Bibliography

    1) AMA: AMA Drug Evaluations, 6th ed, American Medical Association, Chicago, IL, 1986.
    2) Aderhold RM & Muniz CE: Acute psychosis with amitriptyline and furazolidone. J Am Med Assoc 1970; 213:2080.
    3) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    4) Ali BH & Bartlet AL: Anorexia and antagonism to thiamine utilization in poultry treated with furazolidone. Quart J Exp Physiol 1982; 67:437-448.
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