l suspension, usp , 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.

monitored periodically 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 if hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.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 hemolysis is an indication for discontinuing nitrofurantoin oral suspension, usp; hemolysis ceases when the drug is withdrawn.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 oral suspension, 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 at least 3 days after sterility of the urine is obtained. continued infection indicates the need for reevaluation. for long-term suppressive therapy in adults, a reduction of dosage to 50 to100 mg at bedtime may be adequate. for long-term suppressive therapy in pediatric patients, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate. see warnings section regarding risks associated with long term therapy.

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 of 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 neurosis, occur rarely. (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, nystagmus, dizziness, headache, and drowsiness have also 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. dermatologic exfoliative dermatitis and erythema multiforme (including stevens-johnson syndrome) have been reported rarely. transient alopecia also has been reported. allergic a lupus-like syndrome associated with pulmonary reactions to nitrofurantoin has been reported. also, angioedema; maculopapular, erythematous, or eczematous eruptions; pruritus; urticaria; anaphylaxis; arthralgia; myalgia; drug fever; and chills have been reported. hypersensitivity reactions present the most frequent spontaneously-reported adverse events in world-wide postmarketing experience with nitrofurantoin formulations. gastrointestinal nausea, emesis, and anorexia occur most often. abdominal pain and diarrhea are less common gastrointestinal reactions. these dose-related reactions can be minimized by reduction of dosage. sialadenitis and pancreatitis have been reported. there have been sporadic reports of pseudomembranous colitis with the use of nitrofurantoin. the onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment. (see warnings ) 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. there are sporadic reports of clostridium difficile superinfections, or pseudomembranous colitis, with the use of nitrofurantoin.

s 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.

phimurium and forward mutations 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 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.