the broader tissue distribution of other therapeutic agents approved for urinary tract infections. consequently, many patients who are treated with nitrofurantoin capsules (macrocrystals) 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 capsules (macrocrystals), other therapeutic agents with broader tissue distribution should be selected. in considering the use of nitrofurantoin capsules (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.

tored 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 if hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.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 hemolysis is an indication for discontinuing nitrofurantoin (macrocrystals); hemolysis ceases when the drug is withdrawn.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 difficil e -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; 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. 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. to report suspected adverse reactions, contact actavis at 1-888-838-2872 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

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.

voproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other acromolecules. as a result of such inactivations, the vital biochemical processes of protein synthesis, aerobic energy metabolism, dna synthesis, rna synthesis, and cell wall synthesis are inhibited. nitrofurantoin is bactericidal in urine at therapeutic doses. the broad-based nature of this mode of action may explain the lack of acquired bacterial resistance to nitrofurantoin, as the necessary multiple and simultaneous mutations of the target macromolecules would likely be lethal to the bacteria. interactions with other antibiotics antagonism has been demonstrated in vitro between nitrofurantoin and quinolone antimicrobials. the clinical significance of this finding is unknown. development of resistance development of resistance to nitrofurantoin has not been a significant problem since its introduction in 1953. cross-resistance with antibiotics and sulfonamides has not been observed, and transferable resistance is, at most, a very rare phenomenon. nitrofurantoin has been shown to be active against most strains of the following bacteria both in vitro and in clinical infections (see indications and usage ): aerobic and facultative gram-positive microorganisms: staphylococcus aureus enterococci (e.g. enterococcus faecalis) aerobic and facultative gram-negative microorganisms: escherichia coli note : while nitrofurantoin has excellent activity against enterococcus faecalis , the majority of enterococcus faecium isolates are not susceptible to nitrofurantoin. at least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (mic) less than or equal to the susceptible breakpoint for nitrofurantoin. however, the efficacy of nitrofurantoin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled trials. aerobic and facultative gram-positive microorganisms: coagulase-negative staphylococci (including staphylococcus epidermidis and staphylococcus saprophyticus ) streptococcus agalactiae group d streptococci viridans group streptococci aerobic and facultative gram-negative microorganisms: citrobacter amalonaticus citrobacter diversus citrobacter freundii klebsiella oxytoca klebsiella ozaenae note : some strains of enterobacter species and klebsiella species are resistant to nitrofurantoin. susceptibility testing : for specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by fda for this drug, please see: https://www.fda.gov/stic .

on should be taken exactly as directed. skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by nitrofurantoin (macrocrystals) or other antibacterial drugs in the future. diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. if this occurs, patients should contact their physician as soon as possible.