Furantoin

238.16

238.16

200-646-5

DTXSID7020972

ORANGE-YELLOW NEEDLES FROM DIL ACETIC ACID|LEMON-YELLOW CRYSTALS OR FINE POWDER|Yellow powder

J01XE01

29349990

121

-0.5

yellow crystalline

1.5824 (rough estimate)

263 °C

380.75°C (rough estimate)

1.52 (20ºC)

H2O: <0.01 g/100 mL at 19 ºC;DMF: soluble 50mg/mL

0-6°C

LD50 oral in rat: 604mg/kg

ODORLESS

HAS BITTER AFTERTASTE

7.2None

pKa= 7.2

dec 270-272 °C

Insoluble in water.

Amides and Imides

NITROFURANTOIN is sensitive to light. This chemical is incompatible with alkalis. It is also incompatible with strong oxidizers and strong acids. It decomposes on contact with metals other than stainless steel and aluminum. (NTP, 1992)

III

6.1(b)

2811

3

22-42/43

22-36/37-45

MU2800000

Xn

Stability Stable, but light-sensitive. Combustible. Incompatible with strong oxidizing agents, strong alkalies, strong acids. Decomposes upon contact with most metals other than stainless steel and aluminium.

P201, P202, P261, P264, P270, P272, P280, P281, P285, P301+P312, P302+P352, P304+P341, P308+P313, P321, P330, P333+P313, P342+P311, P363, P405, P501

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

GLECKMAN R ET AL; DRUG THERAPY REVIEWS: NITROFURANTOIN; AM J HOSP PHARM 36(MARCH) 342 (1979). REVIEW WITH 237 REFERENCES ON ANTIMICROBIAL SPECTRUM, PHARMACOLOGY, THERAPEUTIC USES, ADVERSE REACTIONS, & MECHANISM OF ACTION.|CADWALLADER DE; BIOAVAILABILITY MONOGRAPH: NITROFURANTOIN; J AM PHARM ASSOC NS15(JULY) 409 (1975). BRIEF REVIEW OF FACTORS AFFECTING NITROFURANTOIN BIOAVAILABILITY IS PRESENTED.|DHHS/NTP; Toxicology & Carcinogenesis Studies of Nitrofurantoin in F344/N Rats and B6C3F1 Mice (Feed Studies) Technical Report Series No. 341 (1989) NIH Publication No. 89-2597

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H302 (93.41%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P272, P280, P281, P285, P301+P312, P302+P352, P304+P341, P308+P313, P321, P330, P333+P313, P342+P311, P363, P405, and P501|Aggregated GHS information provided by 91 companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this material from exposure to light, and store it in a freezer. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

IDENTIFICATION: Nitrofurantoin is an urninary antiseptic and antiinfective drug. It is a lemon yellow solid crystalline material. It is very sightly soluble in water and alcohol. It is soluble in diethylformamide. In the treatment of initial or recurrent urinary tract infections caused by susceptible gram positive and gram negative bacteria including most strains of Escherischia coli. Enterobacter and Klebsiella species are less susceptible and Pseudomonas and most strains of Proteus are resistant to nitrofurantoin. Nitrofurantoin is ineffective in systemic bacterial infections in blood or tissues outside the urinary tract. HUMAN EXPOSURE: Main risks and target organs: The most frequent adverse effects include anorexia, nausea and vomiting. Nitrofurantoin has also been associated with neurological and central nervous system, hepatic, hematological, pulmonary and dermatological toxicity. Apart from gastrointestinal tract symptoms, acute reactions as a result of overdosage of nitrofurantoin have not been reported. Symptoms of toxicity are generally due to hypersensitivity to the drug. Contraindications: Nitrofurantoin is contraindicated in patients who are hypersensitive to the drug or to furan derivatives. It is also relatively contraindicated in renal impairment, diabetes mellitus, electrolyte imbalance, vit.B deficiency as there is an increased risk of developing peripheral neuropathy in these situations. If it has to be used in these cases, extreme care should be taken and treatment stopped at the first sign of toxicity. Hemolysis frequently occurs in Glucose-6-phosphate dehydrogenase deficient patients who take nitrofurantoin. Discontinuation of the drug will often reverse this effect. Nitrofurantoin is contraindicated in pregnant women at term (38-42 weeks gestation) and it should not be administered during labor or just prior to labor to avoid precipitation of hemolytic anemia in the neonate. Neonates are at high risk of hemolysis induced by nitrofurantoin due to their immature enzyme systems. Routes of exposure: Oral: This is the most common route of entry. Absorption by route of exposure: Nitrofurantoin is readily absorbed from the gastrointestinal tract. Absorption occurs mainly in the small intestine. The microcrystalline form of the drug (in suspension, tablets or capsules) is absorbed faster than the macrocrystalline form (in capsules). Presence of food in the gastrointestinal tract or delayed gastric emptying increases the extent of absorption (enhancing the dissolution rate of the drug). Bioavailability is a mean of 87% when taken on an empty stomach, and increases to a mean of 94% when ingested with food. Peak plasma concentrations following a single oral dose are usually attained at 1 to 2 hours after ingestion. Distribution by route of exposure: Nitrofurantoin is 25 to 90% bound to plasma protein. It crosses the placenta and is excreted in the milk. Biological half-life by route of exposure: The plasma half life is approximately 20 to 60 minutes in adults with normal renal function after a therapeutic oral dose. The half-life is prolonged in patients with impaired renal function. Metabolism: Approximately 2/3 of a dose is metabolized in the liver. A small fraction is reduced to aminofurantoin. Elimination by route of exposure: 20 to 44% of an oral dose is excreted unchanged in the urine within 24 hours. 1% is excreted as aminofurantoin. Nitrofurantoin is dialyzable. Mode of action: Toxicodynamics: Nitrofurantoin causes hepatic injury (acute and chronic) through an immunological or metabolic mechanism. Cholestatic jaundice and hepatocellular damage result in elevation of alkaline phosphatase and aspartate transaminase levels. Development of antinuclear antibodies and antismooth muscle antibodies has also been reported. Pulmonary toxicity is attributed to nitrofurantoin production of superoxide anion free radicals with subsequent chain reactions and uncontrolled destructive oxidation, suggested that nitrofurantoin mediated oxidant injury to the lung may be due to direct cytotoxicity or indirectly through recruitment of activated neutrophils. Nitrofurantoin can cause an acute non-cardiogenic pulmonary edema, or subacute interstitial pneumonitis which may progress to interstitial fibrosis. The acute reaction is generally considered to be a hypersensitivity reaction. There is evidence pointing to an immunological mechanism for injury and an increase in T-Lymphocytes in broncheo-alveolar lavage. Peripheral neuropathy is a complication of nitrofurantoin therapy especially in patients with pre-existing renal impairment or diabetes mellitus. Nitrofurantoin triggers a degenerative process in the nerve cell axon with subsequent impairment of sensation and motor strength in the distal extent of the axonal process. Pharmacodynamics: Nitrofurantoin is bacteriostatic or bacteriocidal depending on the concentration and the susceptibility of the microorganism. Its antibacterial activity is enhanced in an acidic pH. It is thought that nitrofurantoin is reduced by bacterial flavoprotein enzymes to an active intermediate which inhibits the microorganism's proteins, DNA, RNA and cell wall synthesis. Nitrofurantoin is active against most strains of Gram positive and Gram negative urinary tract pathogens but generally less active against most strains of Klebsiella, Enterobacter, Pseudomonas and Proteus. Toxicity: Human data: Adults: Acute toxic exposures to nitrofurantoin have not been reported and there have been no acute ingestions causing fatalities. No toxic or lethal levels have been determined for nitrofurantoin. However there are a number of adverse effects and hypersensitivity reactions reported which have included fatalities. The duration of exposure before the onset of symptoms of acute pulmonary toxicity varies from two or three days to several weeks. Teratogenicity: case of a 14 month old girl with asymmetrical paralysis limited to the upper limbs with signs suggesting an early prenatal onset was reported. Nitrofurantoin and Bendectin (R) taken during early pregnancy were suspected to be the cause. Mutagenicity: There are data demonstrating mutagenicity in human cells Interactions: Food significantly enhances the bioavailability and duration of the therapeutic concentration of nitrofurantoin. Uricosuric agents (probenecid or sulfinpyrazone) may inhibit renal excretion of nitrofurantoin and hence increase its plasma level, reduce its effectiveness, and increase its toxicity. Antacids: specifically magnesium trisilicate were reported to decrease the rate and extent of nitrofurantoin absorption through an adsorption mechanism. Quinolones antibacterial activity in vitro is antagonized by nitrofurantoin. It is possible that this interaction could occur in vivo as well. Drugs which acidify the urine decrease the excretion of nitrofurantoin. Main adverse effects: The most frequent adverse effects of nitrofurantoin are anorexia, nausea, and vomiting, which are dose related. Peripheral polyneuropathy and optic neuritis are serious adverse effects of nitrofurantoin and call for immediate withdrawal of the drug. They occur especially in pre-existing renal impairment and the presence of vitamin B deficiency. Peripheral neuropathy was reported in 10 month to 18 year old children. Hepatic damage with nitrofurantoin is reversible on discontinuation of the drug. Hepatic reactions range from acute self-limiting hepatitis to chronic active hepatitis and necrosis associated with long term use. Pulmonary hypersensitivity reactions to nitrofurantoin can be life threatening and nitrofurantoin should be stopped immediately on occurance of symptoms. Impaired pulmonary function may remain even after cessation of therapy. Deaths as a result of cardiopulmonary collapse and of alveolar hemorrhage have been reported. Hematological disorders - and of special significance, hemolytic anaemia associated with use in patients with G-6-PD deficiency have been reported in association with nitrofurantoin use. Additional hematologic effects include leukopenia, granulocytopenia, agranulocytosis, thrombocytopenia, and aplastic anemia. Dermatologic reactions include Stevens Johnson syndrome and other rashes. ANIMAL STUDIES: Carcinogenicity: Nitrofurantoin does not appear to be carcinogenic. There is increased ovarian cancer in mice with chronic, high dose administration. It was found to be carcinogenic in B6C3F female mice and in F344/N male rats. Teratogenicity: There is no evidence to link nitrofurantoin to birth defects in animals.

CONCURRENT ADMIN OF PROBENECID, PARTICULARLY IN HIGH DOSES, DECR RENAL CLEARANCE OF NITROFURANTOIN & INCR SERUM LEVEL... INTERACTION MAY LEAD TO NITROFURANTOIN-INDUCED TOXICITY (EG, POLYNEUROPATHIES) OR DECR NITROFURANTOIN EFFICACY AS URINARY TRACT ANTI-INFECTIVE AGENT.|IN VITAMIN E-DEFICIENT CHICKS, ADMINISTRATION OF SELENIUM HAD A PROTECTIVE EFFECT AGAINST NITROFURANTOIN TOXICITY.|ACETYLSALICYLIC ACID REDUCED THE SOLUBILITY OF NITROFURANTOIN IN ARTIFICIAL INTESTINAL JUICE. SPECTROPHOTOMETRY INDICATED FORMATION OF A COMPLEX BETWEEN THE TWO IN SOLUTION. IN MODEL ABSORPTION STUDIES IN VITRO, ACETYLSALICYLIC ACID DID NOT AFFECT THE DIFFUSION RATE CONSTANT OF NITROFURANTOIN IN SOLUTION ACROSS AN ARTIFICIAL LIPID MEMBRANE. COADMINISTRATION STUDIES IN ADULT HUMANS SHOWED THAT ACETYLSALICYLIC ACID REDUCED THE TOTAL URINARY EXCRETION OF NITROFURANTOIN.|Concurrent use of /hemolytics/ with nitrofurantoin may increase the potential for toxic side effects.|For more Interactions (Complete) data for NITROFURANTOIN (10 total), please visit the HSDB record page.

LD50 Rat oral 604 mg/kg|LD50 Mouse oral 360 mg/kg

... Toxicology and carcinogenesis studies of nitrofurantoin were conducted by admin nitrofurantoin (greater than 99% pure) in feed to groups of F344/N rats and B6C3F1 mice of each sex for ... Two yr studies of nitrofurantoin were conducted by feeding diets containing 0, 1,300, or 2,500 ppm nitrofurantoin to groups of 50 male F344/N rats and to groups of 50 male and female B6C3F1 mice for 103 wk. Groups of 50 female F344/N rats were fed diets containing 0, 600, or 1,300 ppm nitrofurantoin on the same schedule. Conclusions. Under the conditions of these 2 yr feed studies, there was some evidence of carcinogenic activity of nitrofurantoin for male F344/N rats as shown by increased incidences of uncommon kidney tubular cell neoplasms. Uncommon osteosarcomas of the bone and neoplasms of the subcutaneous tissue were observed in dosed male rats. Incidences of interstitial cell adenomas of the testis and neoplasms of the preputial gland were decreased in the 2,500-ppm group of male rats. There was no evidence of carcinogenic activity of nitrofurantoin for female F344/N rats fed diets containing 600 ppm or 1,300 ppm for 2 yr. Female rats may have been able to tolerate higher doses. There was no evidence of carcinogenic activity of nitrofurantoin for male B6C3F1 mice fed diets containing 1,300 ppm or 2,500 ppm for 2 yr. There was clear evidence of carcinogenic activity of nitrofurantoin for female B6C3F1 mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulosa cell tumors of the ovary.|Nitrofurantoin, administered via dosed feed, was tested for its effects on fertility & reproduction in Swiss CD-l mice according to the Continuous Breeding protocol. Based on results of a dose-finding study (Task 1), 0.03, 0.06, & 0.12% (300, 600, & 1,200 ppm) levels were chosen to investigate effects on fertility & reproduction. Male & female mice were continuously exposed for a 7-day precohabitation & a 98-day cohabitation period (Task 2). Subsequently, the control & 0.12% groups were used in a cross-over mating trial (Task 3) to determine the sex affected by chemical treatment. The F1 generation from control, 0.06, & 0.12% groups were also evaluated (Task 4). Nitrofurantoin treatment, at up to 0.12% concns, had no apparent effect on parental fertility, number of litters/pair, proportion of pups born alive, sex of live pups, neonatal body weights, & postnatal survival. Nitrofurantoin at 0.12% in feed, significantly reduced dam body weight at delivery & lactation, number of live pups/litter, & pup body weights at postnatal days 7-21. The cross-over mating trial did not reveal any significant effects on mating, fertility or reproduction. Nitrofurantoin disrupted the estrual cycle in the F0 females; there was a significant incr in the % of vaginal smears showing estrus, & a decr in the % of smears indicating diestrus. All parental mice were necropsied. Female body weight was slightly reduced at 0.12%, as was epididymal sperm motility; absolute & adjusted kidney weights of both sexes were increased significantly at 0.12%. There were also testicular lesions in the 0.12% group. The F1 generation showed significant reductions in fertility & live litter size at the 0.12% dose level. Nitrofurantoin at 0.12% significantly increased F1 adjusted kidney weights (both sexes) & reduced testis, epididymis & cauda epididymis weights as well as epididymal sperm concn & motility, & produced testicular lesions. These data show that Nitrofurantoin exhibited reproductive toxicity in the presence of systemic effects.

Anti-Infective Agents, Urinary /SRP: Antibacterial/|NITROFURANTOIN IS BACTERIOSTATIC AT CONCN OF 5-10 UG/ML & BACTERICIDAL AT 100 UG/ML, BUT IT IS NOT KNOWN WHETHER BACTERICIDAL ACTION OCCURS IN VIVO. ANTIBACTERIAL ACTIVITY IS HIGHER IN ACIDIC URINE. ...SUPERSATURATED SOLN OF NITROFURANTOIN DO NOT CAUSE CRYSTALLURIA.|NITROFURANTOIN IS ACTIVE AGAINST MANY STRAINS OF COMMON URINARY TRACT PATHOGENS E COLI, PROTEUS SPECIES, PSEUDOMONAS...ENTEROBACTER, AND STAPHYLOCOCCI, AS WELL AS ENTEROCOCCI, STREPTOCOCCI, CLOSTRIDIA, & BACILLUS SUBTILIS.|...APPROVED ONLY FOR TREATMENT OF URINARY TRACT INFECTIONS CAUSED BY MICROORGANISMS THAT ARE KNOWN TO BE SENSITIVE TO DRUG. ... IT HAS BEEN USED EFFECTIVELY TO PREVENT RECURRENT INFECTIONS & FOR PREVENTION OF BACTERIURIA AFTER PROSTATECTOMY.|For more Therapeutic Uses (Complete) data for NITROFURANTOIN (8 total), please visit the HSDB record page.

A COURSE OF THERAPY SHOULD NOT EXCEED 14 DAYS, & REPEATED COURSES SHOULD BE SEPARATED BY REST PERIODS. ... PREGNANT WOMEN AT TERM, INDIVIDUALS WITH IMPAIRED RENAL FUNCTION (CREATININE CLEARANCE LESS THAN 40 ML/MIN), & CHILDREN BELOW 1 MONTH OF AGE SHOULD NOT RECEIVE NITROFURANTOIN.|Maternal Medication Usually Compatible with Breast-Feeding: Nitrofurantoin: Hemolysis in infant with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. /from Table 6/|...MOST SPECIES OF PROTEUS & PSEUDOMONAS & MANY OF ENTEROBACTER & KLEBSIELLA ARE RESISTANT. ANTIBACTERIAL CONCN ARE NOT ACHIEVED IN PLASMA FOLLOWING INGESTION OF RECOMMENDED DOSES, BECAUSE DRUG IS RAPIDLY ELIMINATED. ...IN PT WITH IMPAIRED GLOMERULAR FUNCTION EFFICACY OF DRUG MAY BE DECR & SYSTEMIC TOXICITY INCR.|INJECTION OF NITROFURANTOIN SODIUM IS INDICATED ONLY FOR USE IN ACUTELY ILL PT WHO CANNOT TOLERATE ORAL NITROFURANTOIN. /SODIUM NITROFURANTOIN/|For more Drug Warnings (Complete) data for NITROFURANTOIN (31 total), please visit the HSDB record page.

.../IT/ IS RAPIDLY & COMPLETELY ABSORBED FROM GI TRACT. ... PLASMA HALF-LIFE IS 0.3 TO 1 HR; ABOUT 40% IS EXCRETED UNCHANGED INTO URINE. AVG DOSE OF NITROFURANTOIN YIELDS URINE CONCN OF APPROX 200 UG/ML. ... RATE OF EXCRETION IS LINEARLY RELATED TO CREATININE CLEARANCE...|CLINICAL STUDIES...INDICATE THAT IN NORMAL FASTING INDIVIDUALS, LESS NITROFURANTOIN IS ABSORBED & AT SLOWER RATE FROM MACROCRYSTALLINE THAN MICROCRYSTALLINE FORM. PRESENCE OF FOOD IN INTESTINE DELAYS ABSORPTION OF BOTH FORMS APPRECIABLY, INCR PEAK LEVELS OF MACROCRYSTALLINE COMPD, BUT NOT MICROCRYSTALLINE COMPD, ENHANCES BIOAVAILABILITY OF BOTH FORMS, & PROLONGS DURATION OF THERAPEUTIC URINARY CONCN.|ENHANCEMENT OF...ABSORPTION BY FOOD RANGED FROM 20 TO 400%, WITH GREATEST EFFECT OCCURRING WITH LEAST SOLUBLE DOSAGE FORMS. .../IT/ IS INEFFICIENTLY ABSORBED FROM RECTAL SUPPOSITORIES...|NITROFURANTOIN ABSORPTION IS SIGNIFICANTLY INCR IN MAN FROM A DRUG-DEOXYCHOLIC ACID CO-PRECIPITATE COMPARED WITH PHYS MIXT, & FASTER ABSORPTION...FROM CO-PRECIPITATE WAS ASSOCIATED WITH FASTER IN VITRO DISSOLUTION RATE. ... EXCRETED IN BILE OF DOGS & ABOUT 1/3 OF THAT EXCRETED IS REABSORBED FROM INTESTINE WITHIN 3 HR.|For more Absorption, Distribution and Excretion (Complete) data for NITROFURANTOIN (13 total), please visit the HSDB record page.

AFTER DOSE OF 0.200 MG/KG, 22% IS EXCRETED IN URINE AS N-(5-NITROFURFURYLIDENEAMINO)-2-IMIDAZOLINE-ONE. /FROM TABLE/|READILY DEGRADED BY ALL /BODY/ TISSUES (EXCEPT BLOOD) INTO INACTIVE METABOLITES-HYDROXYLAMINO COMPD & AMINOFURALDEHYDENITROFURIC ACID. /HUMAN, ORAL/|AFTER NITROFURANTOIN (50 MG) IV INFUSION, 47% OF THE DOSE WAS EXCRETED UNCHANGED IN THE URINE AND 1.2% WAS RECOVERED AS THE REDUCED METABOLITE AMINOFURANTOIN.|Nitrofurantoin is partially metabolized, mainly in the liver. A small fraction of the drug is reduced to form aminofurantoin.

PLASMA HALF-LIFE IS 0.3 TO 1 HR...|NITROFURANTOIN HALF-LIFE WAS 0.41 HOURS IN ADULTS AND 0.95 HOURS IN 2-WEEK-OLD RATS.

MICROSOMAL AND SOLUBLE FRACTIONS FROM BOTH RAT LIVER AND LUNG MEDIATED THE COVALENT BINDING OF (14)C-LABELED NITROFURANTOIN (I) TO TISSUE MACROMOLECULES IN VITRO. OXYGEN STRONGLY INHIBITED THE BINDING IN BOTH FRACTIONS, AND CARBON MONOXIDE FAILED TO INHIBIT THE BINDING IN MICROSOMAL PREPARATIONS, INDICATING ACTIVATION OF I IN BOTH SYSTEMS BY NITROREDUCTION RATHER THAN OXIDATION OF THE FURAN RING. MICROSOMAL NITROREDUCTION AND COVALENT BINDING OF I WERE INHIBITED BY AN ANTIBODY AGAINST NADPH-CYTOCHROME C REDUCTASE AND COVALENT BINDING WAS ENHANCED BY THE ADDITION OF FAD. IN SOLUBLE FRACTIONS, MAXIMUM RATES OF COVALENT BINDING WERE OBTAINED IN THE PRESENCE OF NADH AND HYPOXANTHINE, AND IT WAS INHIBITED BY ALLOPURINOL, A XANTHINE OXIDASE INHIBITOR. REDUCED GLUTATHIONE DECREASED COVALENT BINDING OF I IN BOTH MICROSOMAL AND SOLUBLE FRACTIONS OF LIVER AND LUNG, BUT THE RATE OF NITROREDUCTION WAS UNAFFECTED.|THE HYPOTHESIS IS PRESENTED THAT THE TOXICITY OF NITROFURANS SUCH AS NITROFURANTOIN (I), WHICH ARE USED IN COMMERCIAL POULTRY PRODUCTION, IS DUE TO OXIDATIVE METABOLIC STRESS CAUSED BY THE O2- FREE RADICAL FORMED DURING METABOLISM OF THE COMPOUNDS.

SYMPTOMS: Symptoms of exposure to this compound may include fever, nausea, vomiting, diarrhea, chills, cough, dyspnea, chest pain, pulmonary infiltration, hepatitis, eosinophilia, interstitial pneumonitis or fibrosis, hemolytic anemia, megaloblastic anemia, cholestatic jaundice, granulocytopenia, leukopenia and headache. Other symptoms may include anorexia, malaise, abdominal pain, acute, subacute and chronic pulmonary reactions, insidious onset of pulmonary reactions, consolidation or pleural effusion on x-ray, altered pulmonary function, exfoliative dermatitis, multiforme, maculopapular, erythematous or eczematous eruption, pruritus, urticaria, anaphylaxis, angioedema, asthmatic attack in persons with a history of asthma, arthralgia, pancreatitis, sialadenitis, agranulocytosis, thrombocytopenia and dizziness. It can cause various neurological disorders, vertigo, drowsiness, nystagmus, muscular aches, hypersensitivity reactions and hepatocellular damage. Severe polyneuropathies with demyelination and degeneration of both sensory and motor nerves have been reported. Signs of denervation and muscular atrophy result. Other symptoms may include bleeding, acute polyneuritis, cerebellar dysfunction and circulatory collapse. It can cause ataxic gait. Eye contact may result in severe itching and burning of the eyes with excessive tearing, retrobulbar neuritis and vertical diplopia. Large doses have decreased spermatogenesis through direct action on the seminiferous tubules. Other symptoms include ataxia and changes in urine composition. ACUTE/CHRONIC HAZARDS: This compound is harmful if swallowed or inhaled. It may cause irritation. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide and nitrogen oxides. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

ADULT RESPIRATORY DISTRESS SYNDROME ASSOCIATED WITH ACUTE NITROFURANTOIN USE IS DESCRIBED. THE PATIENT WAS SUCCESSFULLY MANAGED WITH CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) THROUGH A TIGHTLY FITTING FACE MASK; CLINICAL DETERIORATION FOLLOWED DISCONTINUATION OF THE CPAP, WITH IMPROVEMENT OCCURRING WHEN IT WAS RESTARTED. ACUTE NITROFURANTOIN PLEUROPULMONARY REACTIONS ARE REVIEWED.

AN ASYMPTOMATIC PALPABLE LIVER TUMOR DEVELOPED IN A SIX-YEAR-OLD GIRL SEVEN MONTHS AFTER COMMENCEMENT OF PROPHYLACTIC NITROFURANTOIN THERAPY FOR RECURRENT URINARY TRACT INFECTIONS. THE PATHOLOGICAL FINDINGS WERE TYPICAL FOR FOCAL NODULAR HYPERPLASIA (FNH) OF THE LIVER.|In a study of 757 courses of nitrofurantoin in hospitalized patients, the overall frequency of adverse reactions was 9.2%. Toxic reactions constituted 5.1% of adverse effects; the remainder were allergic.|...drug intake and pregnancy outcome were studied in a series of 50,282 women in 1959-1965, 83 women had been exposed to nitrofurantoin during the first trimester of pregnancy. Six malformed children were born in the exposed group, giving a standardized nonsignificant relative risk of 1.07.|Chronic use...for 6 months to 6 yr has resulted in cases of pulmonary fibrosis. Most cases have been reversible following discontinuation of the drug and institution of steroid therapy. It appears to occur most frequently in postmenopausal women.|LARGE DOSES...DEPRESS SPERMATOGENESIS BY ACTING DIRECTLY ON SEMINIFEROUS TUBULES. USUAL THERAPEUTIC DOSES APPEAR TO HAVE NO SUCH EFFECT.

NITROFURANTOIN SODIUM; SODIUM COMPOUNDS, WITH 1-((5-NITROFURFURYLIDENE)AMINO)HYDANTOIN; & SODIUM FURADANTIN. /SODIUM SALT/|NITROFURANTOIN, USP (FURADANTIN, OTHERS), IS AVAIL IN TABLETS CONTAINING 50 OR 100 MG OF DRUG & IN ORAL SUSPENSION CONTAINING 25 MG/5 ML. NITROFURANTOIN MICROCRYSTALS (MACRODANTIN) ARE AVAIL IN 25-, 50-, & 100-MG CAPSULES.|Grade: USP

2,4-Imidazolidinedione, 1-[[(5-nitro-2-furanyl)methylene]amino]-: ACTIVE

NITROFURANTOIN WAS DETERMINED IN BULK, CAPSULES, TABLETS, AND SUSPENSIONS BY A COLORIMETRIC METHOD BASED ON THE REACTION OF NITROFURANTOIN WITH ORCINOL IN AN ALKALINE MEDIUM AND THE MEASUREMENT OF ABSORBANCE OF THE RESULTING ORANGE COLOR AT 435 NM.

THE HPLC PROCEDURE DESCRIBED FOR DETECTION OF NITROFURANTOIN IN PLASMA, URINE & BIOLOGICAL FLUIDS REQUIRES 0.2 ML OF SAMPLE, SHOWS LINEAR RELATIONSHIP IN RANGE OF 0.02 TO 200 MG/L & CAN BE PERFORMED IN 9 MIN.|AN HPLC CHROMATOGRAPHY METHOD FOR DETECTION OF NITROFURANTOIN & OTHER NITROFURAN DERIV IN BLOOD & URINE IS DESCRIBED. DETECTION LIMIT WAS 0.02 MUG/ML.|NITROFURANTOIN WAS DETERMINED IN BLOOD SERUM BY DIFFERENTIAL PULSE POLAROGRAPHY OR HPLC. THE DETECTION LIMIT WITH 5 ML SERUM WAS 0.2 MUG/ML WITH THE HPLC METHOD AND 0.4 MUG/ML WITH POLAROGRAPHY.

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