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Nitrofurantoin

Medically reviewed on March 25, 2018

Pronunciation

(nye troe fyoor AN toyn)

Dosage Forms

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

Suspension, Oral:

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.

  • Furadantin
  • Macrobid
  • Macrodantin

Pharmacologic Category

  • Antibiotic, Miscellaneous

Pharmacology

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.

Absorption

Well absorbed; macrocrystalline is absorbed more slowly due to slower dissolution (causes less GI distress)

Distribution

Vd: 0.8 L/kg

Metabolism

Body tissues (except plasma) metabolize 60% of drug to inactive metabolites

Excretion

Suspension: Urine (~40%) and feces (small amounts) as metabolites and unchanged drug

Macrocrystals: Urine (20% to 25% as unchanged drug)

Half-Life Elimination

20-60 minutes; prolonged with renal impairment

Protein Binding

60% to 90%

Special Populations: Renal Function Impairment

Nitrofurantoin accumulates in serum.

Use: Labeled Indications

Cystitis, acute uncomplicated:

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. May also be used for chronic suppression of recurrent UTIs.

Limitations of use: Not indicated for treatment of pyelonephritis or perinephric abscess

Contraindications

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.

Dosing: Adult

Cystitis, acute uncomplicated, treatment:

Nitrofurantoin monohydrate/macrocrystals (Macrobid): Oral: 100 mg twice daily for 5 days (Gupta 2011; Gupta 2007).

Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 50 to 100 mg every 6 hours; administer for 7 days or at least 3 days after obtaining sterile urine.

UTI, prophylaxis: Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 50 to 100 mg once daily at bedtime.

Dosing: Geriatric

Avoid use; alternative agents preferred. Refer to adult dosing.

Dosing: Pediatric

UTI, treatment:

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.

Administration

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.

Dietary Considerations

Take with meals to improve absorption and decrease adverse effects.

Storage

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.

Drug Interactions

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. 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

Spironolactone: Nitrofurantoin may enhance the hyperkalemic effect of Spironolactone. Monitor therapy

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

Test Interactions

False-positive urine glucose (Benedict's and Fehling's methods); no false positives with enzymatic tests

Adverse Reactions

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, 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

Miscellaneous: Fever

Postmarketing and/or case reports: Hepatotoxicity (idiosyncratic) (Chalasani, 2014)

Warnings/Precautions

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.

Disease-related concerns:

• 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 (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.

Special populations:

• 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).

Other warnings/precautions:

• Appropriate use: Pyelonephritis: Not indicated for the treatment of pyelonephritis or perinephric abscesses.

Monitoring Parameters

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)

Pregnancy Considerations

Adverse effects have not been observed in animal reproduction studies. Nitrofurantoin crosses the placenta (Perry 1967) and maternal serum concentrations may be lower in pregnancy (Philipson 1979). Current studies evaluating maternal use of nitrofurantoin during pregnancy and the development of birth defects have had mixed results (ACOG 2011). An increased risk of neonatal jaundice was observed following maternal nitrofurantoin use during the last 30 days of pregnancy (Nordeng 2013). Nitrofurantoin may be used to treat infections in pregnant women; 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 2011). Nitrofurantoin is contraindicated in pregnant patients at term (38-42 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 considered in pregnant women with G-6-PD deficiency (Nordeng 2013).

Patient Education

• 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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