the broader tissue distribution of other therapeutic agents approved for urinary tract infections. consequently, many patients who are treated with nitrofurantoin capsules, usp (monohydrate/macrocrystals) are predisposed to persistence or reappearance of bacteriuria (see clinical studies ). urine specimens for culture and susceptibility testing should be obtained before and after completion of therapy. if persistence or reappearance of bacteriuria occurs after treatment with nitrofurantoin capsules, usp (monohydrate/macrocrystals), other therapeutic agents with broader tissue distribution should be selected. in considering the use of nitrofurantoin capsules, usp (monohydrate/macrocrystals), lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antimicrobial resistance when agents with broader tissue distribution are utilized.

for changes in biochemical tests that would indicate liver injury. if hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken. neuropathy: peripheral neuropathy, which may become severe or irreversible, has occurred. fatalities have been reported. conditions such as renal impairment (creatinine clearance under 60 ml per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin b deficiency and debilitating disease may enhance the occurrence of peripheral neuropathy. patients receiving long-term therapy should be monitored periodically for changes in renal function. optic neuritis has been reported rarely in postmarketing experience with nitrofurantoin formulations. hemolytic anemia: cases of hemolytic anemia of the primaquine-sensitivity type have been induced by nitrofurantoin. hemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. this deficiency is found in 10 percent of blacks and a small percentage of ethnic groups of mediterranean and near-eastern origin. hemolysis is an indication for discontinuing nitrofurantoin; hemolysis ceases when the drug is withdrawn. clostridium difficile -associated diarrhea: clostridium difficile associated diarrhea (cdad) has been reported with use of nearly all antibacterial agents, including nitrofurantoin, and may range in severity from mild diarrhea to fatal colitis. treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of c. difficile . c. difficile produces toxins a and b which contribute to the development of cdad. hypertoxin producing strains of c. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. cdad must be considered in all patients who present with diarrhea following antibiotic use. careful medical history is necessary since cdad has been reported to occur over two months after the administration of antibacterial agents. if cdad is suspected or confirmed, ongoing antibiotic use not directed against c. difficile may need to be discontinued. appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of c. difficile and surgical evaluation should be instituted as clinically indicated.

or after antimicrobial treatment (see warnings ). neurologic: peripheral neuropathy, which may become severe or irreversible, has occurred. fatalities have been reported. conditions such as renal impairment (creatinine clearance under 60 ml per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin b deficiency and debilitating diseases may increase the possibility of peripheral neuropathy (see warnings ). asthenia, vertigo and nystagmus also have been reported with the use of nitrofurantoin. benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis and psychotic reactions have been reported rarely. bulging fontanels, as a sign of benign intracranial hypertension in infants, have been reported rarely. respiratory: chronic, subacute, or acute pulmonary hypersensitivity reactions may occur with the use of nitrofurantoin. chronic pulmonary reactions generally occur in patients who have received continuous treatment for six months or longer. malaise, dyspnea on exertion, cough and altered pulmonary function are common manifestations which can occur insidiously. radiologic and histologic findings of diffuse interstitial pneumonitis or fibrosis, or both, are also common manifestations of the chronic pulmonary reaction. fever is rarely prominent. the severity of chronic pulmonary reactions and their degree of resolution appear to be related to the duration of therapy after the first clinical signs appear. pulmonary function may be impaired permanently, even after cessation of therapy. the risk is greater when chronic pulmonary reactions are not recognized early. in subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form. upon cessation of therapy, recovery may require several months. if the symptoms are not recognized as being drug-related and nitrofurantoin therapy is not stopped, the symptoms may become more severe. acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray and eosinophilia. acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. resolution often is dramatic (see warnings ). changes in ekg (e.g., non-specific st/t wave changes, bundle branch block) have been reported in association with pulmonary reactions. cyanosis has been reported rarely. hepatic: hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis and hepatic necrosis, occur rarely (see warnings ). allergic: lupus-like syndrome associated with pulmonary reaction to nitrofurantoin has been reported. also, angioedema; maculopapular, erythematous, or eczematous eruptions; anaphylaxis; arthralgia; myalgia; drug fever; chills; and vasculitis (sometimes associated with pulmonary reactions) have been reported. hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with nitrofurantoin formulations. dermatologic: exfoliative dermatitis and erythema multiforme (including stevens-johnson syndrome) have been reported rarely. hematologic: cyanosis secondary to methemoglobinemia has been reported rarely. miscellaneous: as with other antimicrobial agents, superinfections caused by resistant organisms, e.g., pseudomonas species or candida species, can occur. in clinical trials of nitrofurantoin, the most frequent laboratory adverse events (1% to 5%), without regard to drug relationship, were as follows: eosinophilia, increased ast (sgot), increased alt (sgpt), decreased hemoglobin, increased serum phosphorus. the following laboratory adverse events also have been reported with the use of nitrofurantoin: glucose-6-phosphate dehydrogenase deficiency anemia (see warnings ), agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia. in most cases, these hematologic abnormalities resolved following cessation of therapy. aplastic anemia has been reported rarely. to request medical information or to report suspected adverse reactions, contact amneal pharmaceuticals at 1-877-835-5472 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

mes the human dose on a mg/kg basis. the relationship of this finding to potential human carcinogenesis is presently unknown. because of the uncertainty regarding the human implications of these animal data, this drug should be used during pregnancy only if clearly needed. labor and delivery see contraindications .

ghly soluble in urine, to which it may impart a brown color. when nitrofurantoin is administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%.

urium and forward mutations in l5178y mouse lymphoma cells. nitrofurantoin induced increased numbers of sister chromatid exchanges and chromosomal aberrations in chinese hamster ovary cells but not in human cells in culture. results of the sex-linked recessive lethal assay in drosophila were negative after administration of nitrofurantoin by feeding or by injection. nitrofurantoin did not induce heritable mutation in the rodent models examined. the significance of the carcinogenicity and mutagenicity findings relative to the therapeutic use of nitrofurantoin in humans is unknown. the administration of high doses of nitrofurantoin to rats causes temporary spermatogenic arrest; this is reversible on discontinuing the drug. doses of 10 mg/kg/day or greater in healthy human males may, in certain unpredictable instances, produce a slight to moderate spermatogenic arrest with a decrease in sperm count.