roader tissue distribution of other therapeutic agents approved for urinary tract infections. consequently, many patients who are treated with nitrofurantoin macrocrystals capsules are predisposed to persistence or reappearance of bacteriuria. 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 macrocrystals capsules, other therapeutic agents with broader tissue distribution should be selected. in considering the use of nitrofurantoin macrocrystals capsules, 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.

itored 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 if hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.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 hemolysis is an indication for discontinuing nitrofurantoin macrocrystals; hemolysis ceases when the drug is withdrawn.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.

uire 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 ). 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 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. 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 represent the most frequent spontaneously-reported adverse events in worldwide 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. laboratory adverse events: the following laboratory adverse events have been reported with the use of nitrofurantoin: increased ast (sgot), increased alt (sgpt), decreased hemoglobin, increased serum phosphorus, eosinophilia, 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.