Medically reviewed on Nov 15, 2018
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as macrocrystals:
Macrodantin: 25 mg
Macrodantin: 50 mg, 100 mg [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Generic: 25 mg, 50 mg, 100 mg
Capsule, Oral, as monohydrate/macrocrystals:
Macrobid: 100 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #10 (quinoline yellow)]
Generic: 100 mg
Furadantin: 25 mg/5 mL (230 mL [DSC])
Furadantin: 25 mg/5 mL (230 mL) [contains methylparaben, propylparaben]
Generic: 25 mg/5 mL (230 mL, 240 mL)
Brand Names: U.S.
- Antibiotic, Miscellaneous
Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates that inactivate or alter bacterial ribosomal proteins leading to inhibition of protein synthesis, aerobic energy metabolism, DNA, RNA, and cell wall synthesis. 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.
Well absorbed; macrocrystalline is absorbed more slowly due to slower dissolution (causes less GI distress)
Vd: 0.8 L/kg
Body tissues (except plasma) metabolize 60% of drug to inactive metabolites
Suspension: Urine (~40%) and feces (small amounts) as metabolites and unchanged drug
Macrocrystals: Urine (20% to 25% as unchanged drug)
20 to 60 minutes; prolonged with renal impairment
60% to 90%
Special Populations: Renal Function Impairment
Nitrofurantoin accumulates in serum.
Use: Labeled Indications
Cystitis, acute uncomplicated, treatment:
Nitrofurantoin monohydrate/macrocrystals (Macrobid): Treatment of acute uncomplicated cystitis caused by susceptible strains of Escherichia coli or Staphylococcus saprophyticus in patients ≥12 years of age
Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Treatment of acute uncomplicated cystitis when caused by susceptible strains of E. coli, enterococci, Staphylococcus aureus, and certain susceptible strains of Klebsiella and Enterobacter species
Limitations of use: Not indicated for treatment of pyelonephritis or perinephric abscess
Cystitis, recurrent, prophylaxis: Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Chronic suppression of recurrent UTIs
Anuria, oliguria, or significant impairment of renal function (creatinine clearance [CrCl] <60 mL/minute or clinically significant elevated serum creatinine); previous history of cholestatic jaundice or hepatic dysfunction associated with prior nitrofurantoin use; hypersensitivity to drug or any component of the formulation.
Note: The manufacturer’s contraindication in patients with CrCl <60 mL/minute has been challenged in the literature; limited data suggest that an alternative creatinine clearance threshold may be considered (Oplinger 2013).
Because of the possibility of hemolytic anemia caused by immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38 to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent; also contraindicated in neonates younger than 1 month of age.
Note: Nitrofurantoin is chemically available as nitrofurantoin macrocrystals and nitrofurantoin monohydrate. Two different preparations are available in the US: A combination of nitrofurantoin monohydrate and nitrofurantoin macrocrystals (Macrobid), which is typically dosed twice daily for the treatment of acute infections and a preparation that consists solely of nitrofurantoin macrocrystals (Furadantin, Macrodantin), which is typically dosed 4 times daily for the treatment of acute infections. Regardless of the formulation used, advise patients to administer with food to improve absorption.
Cystitis, acute uncomplicated or acute simple (infection limited to bladder and no signs/symptoms of upper tract, prostate, or systemic infection), treatment: Note: Consider use of a different empiric agent in patients with suspected pyelonephritis, patients who have received nitrofurantoin in the last 3 months, or patients who have had a urine isolate with documented resistance to nitrofurantoin in the last 3 months (Hooton 2018a; Hooton 2018b; IDSA [Gupta 2011]).
Nitrofurantoin monohydrate/macrocrystals (Macrobid): Oral: 100 mg twice daily; treat females for 5 days (Gupta 2007; IDSA [Gupta 2011]) and males for 7 days (based on expert opinion; Hooton 2018b)
Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 50 to 100 mg every 6 hours; treat females for 5 days (Gupta 2007; IDSA [Gupta 2011]) and males for 7 days (Hooton 2018b). Note: The recommended duration of therapy with this formulation is based on the recommendation for the nitrofurantoin monohydrate/macrocrystal formulation as well as expert opinion.
Cystitis, recurrent, prophylaxis: Note: Prophylaxis may be considered in nonpregnant women with bothersome, recurrent uncomplicated cystitis despite nonantimicrobial preventive measures (Albert 2004; Muller 2017). The ideal antibiotic for prophylaxis, as well as the optimal dose, schedule, and duration has not been determined; choice of antibiotic should take into account community patterns of resistance and patient-specific factors (eg, prior efficacy, cost) (Ahmed 2017; Albert 2004; Muller 2017). Prolonged use (>6 months) of nitrofurantoin has been associated with diffuse interstitial pneumonitis and/or pulmonary fibrosis, chronic hepatitis, and the development of neuropathy (Holmberg 1980; manufacturer's labeling).
Nitrofurantoin monohydrate/macrocrystals (Macrobid) (off-label use): Oral: 100 mg once daily at bedtime (Rogers 2004)
Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 50 to 100 mg once daily at bedtime
Postcoital prophylaxis: Females with cystitis temporally related to sexual intercourse:
Nitrofurantoin monohydrate/macrocrystals (Macrobid) (off-label use): Oral: 100 mg as a single dose taken within 2 hours of sexual intercourse (Pfau 1983; Rogers 2004; Sen 2008)
Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 50 to 100 mg as a single dose taken within 2 hours of sexual intercourse (Pfau 1983; Sen 2008)
Avoid use; alternative agents preferred. Refer to adult dosing.
Infants, Children, and Adolescents: Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 5 to 7 mg/kg/day in divided doses every 6 hours (maximum: 400 mg daily). Administer for 7 days or at least 3 days after obtaining sterile urine.
Adolescents: Nitrofurantoin monohydrate/macrocrystals (Macrobid): Oral: 100 mg twice daily for 7 days
UTI, prophylaxis: Infants, Children, and Adolescents: Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 1 to 2 mg/kg/day as a single daily dose or divided every 12 hours (maximum: 100 mg daily) (Bradley 2016)
Dosing: Renal Impairment
CrCl ≥60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
CrCl <60 mL/minute:
Manufacturer's labeling: Use is contraindicated.
Alternate dosing: Limited data suggest nitrofurantoin is safe and effective for short-term treatment of uncomplicated UTI in patients with CrCl 30 to 60 mL/minute (Oplinger 2013; Santos 2016; Singh 2015). The Beers Criteria recommends avoiding use in geriatric patients ≥65 years with a CrCl <30 mL/minute (Beers Criteria [AGS 2015]).
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling. Contraindicated in patients with a previous history of cholestatic jaundice or hepatic dysfunction associated with nitrofurantoin.
Oral: Administer with meals to improve absorption and decrease adverse effects; suspension may be mixed with water, milk, fruit juice, or infant formula. Shake suspension well before use.
Take with meals to improve absorption and decrease adverse effects.
Capsules: Store at controlled room temperature, 15°C to 30°C (59°F to 86°F). Dispense in a tight container using a child-resistant closure.
Oral suspension: Avoid exposure to strong light, which may darken the drug. It is stable when stored between 20°C and 25°C (68°F and 77°F). Protect from freezing. Dispense in glass amber bottles.
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy
Eplerenone: Nitrofurantoin may enhance the hyperkalemic effect of Eplerenone. Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Magnesium Trisilicate: May decrease the serum concentration of Nitrofurantoin. Avoid combination
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Monitor therapy
Norfloxacin: Nitrofurantoin may diminish the therapeutic effect of Norfloxacin. Avoid combination
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy
Probenecid: May increase the serum concentration of Nitrofurantoin. Monitor therapy
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Tetracaine (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
False-positive urine glucose (Benedict's and Fehling's methods); no false positives with enzymatic tests
Frequency not defined.
Cardiovascular: ECG changes (nonspecific ST/T wave changes, bundle branch block)
Central nervous system: Bulging fontanel (infants), chills, confusion, depression, dizziness, drowsiness, headache, malaise, numbness, paresthesia, peripheral neuropathy, pseudotumor cerebri, psychotic reaction, vertigo
Dermatologic: Alopecia, erythema multiforme, exfoliative dermatitis, pruritus, skin rash (eczematous, erythematous, maculopapular), Stevens-Johnson syndrome, urticaria
Endocrine & metabolic: Hyperphosphatemia
Gastrointestinal: Abdominal pain, anorexia, Clostridioides (formerly Clostridium) difficile-associated diarrhea, constipation, diarrhea, dyspepsia, flatulence, nausea, pancreatitis, pseudomembranous colitis, sialadenitis, vomiting
Genitourinary: Urine discoloration (brown)
Hematologic & oncologic: Agranulocytosis, aplastic anemia, eosinophilia, glucose-6-phosphate dehydrogenase deficiency anemia, granulocytopenia, hemoglobin decreased, hemolytic anemia, leukopenia, megaloblastic anemia, thrombocytopenia
Hepatic: Cholestatic jaundice, hepatitis, hepatic necrosis, increased serum transaminases
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity (including acute pulmonary hypersensitivity)
Infection: Superinfection (eg, Pseudomonas or Candida)
Neuromuscular & skeletal: Arthralgia, lupus-like syndrome, myalgia, weakness
Ophthalmic: Amblyopia, nystagmus, optic neuritis
Respiratory: Acute pulmonary reaction (symptoms include chills, chest pain, cough, dyspnea, fever, and eosinophilia), cough, cyanosis, dyspnea, pneumonitis, pulmonary fibrosis (with long-term use), pulmonary infiltration
Postmarketing and/or case reports: Hepatotoxicity (idiosyncratic) (Chalasani 2014)
Concerns related to adverse effects:
• Hepatic reactions: Rare, but severe and sometimes fatal hepatic reactions (eg, cholestatic jaundice, hepatitis, hepatic necrosis) have been associated with use (onset may be insidious); discontinue immediately if hepatitis occurs. Monitor liver function tests periodically. Use is contraindicated in patients with a history of nitrofurantoin associated cholestatic jaundice or hepatic dysfunction.
• Optic neuritis: Postmarketing cases of optic neuritis have been reported.
• Peripheral neuropathy: Has been associated with peripheral neuropathy (rare); risk may be increased in patients with anemia, renal impairment (CrCl <60 mL/minute), diabetes, vitamin B deficiency, debilitating disease, or electrolyte imbalance; use caution.
• Pulmonary toxicity: Acute, subacute, or chronic (usually after 6 months of therapy) pulmonary reactions (possibly fatal) have been observed; if these occur, discontinue therapy immediately. Monitor closely for malaise, dyspnea, cough, fever, radiologic evidence of diffuse interstitial pneumonitis or fibrosis.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Hemolytic anemia: Use caution in patients with G6PD deficiency; may be at increased risk for hemolytic anemia. Discontinue therapy if occurs.
• Renal impairment: Urinary nitrofurantoin concentrations are variable in patients with impaired renal function. The manufacturer contraindicates use in CrCl <60 mL/minute; however, limited data suggest nitrofurantoin is safe and effective for short-term treatment of uncomplicated UTI in patients with CrCl 30 to 60 mL/minute (Cuhna 2017; Oplinger 2013; Santos 2016; Singh 2015). The Beers Criteria recommends avoiding use in geriatric patients ≥65 years with a CrCl <30 mL/minute (Beers Criteria [AGS 2015]).
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
• Elderly: Use in elderly patients, particularly females receiving long-term prophylaxis for recurrent UTIs, has also been associated with an increased risk of hepatic and pulmonary toxicity and peripheral neuropathy. Monitor closely for toxicities during use.
• Pediatric: Use is contraindicated in children <1 month of age (at increased risk for hemolytic anemia).
• Appropriate use: Pyelonephritis: Not indicated for the treatment of pyelonephritis or perinephric abscesses.
Signs of pulmonary reaction; signs of numbness or tingling of the extremities; CBC, periodic liver function tests, periodic renal function tests with long-term use
Pregnancy Risk Factor
B (contraindicated at term)
Nitrofurantoin crosses the placenta (Perry 1967).
Current studies evaluating maternal use of nitrofurantoin during pregnancy and the development of birth defects have had mixed results (ACOG 717 2017). An increased risk of neonatal jaundice was observed following maternal nitrofurantoin use during the last 30 days of pregnancy (Nordeng 2013).
Maternal serum concentrations of nitrofurantoin may be decreased in pregnancy (Philipson 1979). Nitrofurantoin may be used to treat infections during pregnancy; use during the first trimester should be limited to situations where no alternative therapies are available. Prescriptions should be written when clinically appropriate and for the shortest effective duration for confirmed infections (ACOG 717 2017). Nitrofurantoin is contraindicated in pregnant patients at term (38 to 42 weeks' gestation), during labor and delivery, or when the onset of labor is imminent due to the possibility of hemolytic anemia in the neonate. Alternative antibiotics should be used in pregnant patients with G-6-PD deficiency (ACOG 717 2017; Nordeng 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, nausea, vomiting, diarrhea, lack of appetite, abdominal pain, dizziness, fatigue, or urine discoloration. Have patient report immediately to prescriber signs of nerve problems (sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain, or weakness in the arms, hands, legs, or feet), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), involuntary eye movements, loss of strength and energy, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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