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Nitrofurantoin

Medically reviewed by Drugs.com. Last updated on Jul 10, 2020.

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:

Macrobid: 100 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #10 (quinoline yellow)]

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

Suspension, Oral:

Furadantin: 25 mg/5 mL (230 mL [DSC])

Furadantin: 25 mg/5 mL (230 mL [DSC]) [contains methylparaben, propylparaben]

Generic: 25 mg/5 mL (230 mL, 240 mL)

Brand Names: U.S.

  • Furadantin [DSC]
  • 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 to 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, 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, uncomplicated, prophylaxis for recurrent infection: Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Chronic suppression of recurrent urinary tract infections.

Off Label Uses

Bacteriuria, asymptomatic, in pregnancy

Based on the Infectious Diseases Society of America clinical practice guideline for the management of asymptomatic bacteriuria, nitrofurantoin is an effective and recommended agent in the management of asymptomatic bacteriuria (≥105 CFU per mL) in pregnancy.

Data from a randomized, controlled trial support the use of nitrofurantoin for the treatment of asymptomatic bacteriuria in pregnancy [Lumbiganon 2009].

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

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.

Bacteriuria (≥105 CFU per mL), asymptomatic, in pregnancy (off-label use):

Note: Use of nitrofurantoin during the first trimester should be limited to situations where no alternative therapies are available (ACOG 2017; Nordeng 2013); use is contraindicated in pregnant patients at term (38 to 42 weeks' gestation), during labor and delivery, or when the onset of labor is imminent.

Nitrofurantoin monohydrate/macrocrystals (Macrobid): Oral: 100 mg twice daily for 4 to 7 days (IDSA [Nicolle 2019]; Lumbiganon 2009).

Cystitis, acute uncomplicated or acute simple, 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 2019a; Hooton 2019b; 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 2019b).

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 2019b). 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, uncomplicated, prophylaxis for recurrent infection:

Note: Prophylaxis may be considered in nonpregnant women with bothersome, recurrent uncomplicated cystitis despite nonantimicrobial preventive measures. The optimal duration of prophylaxis has not been established; duration ranges from 3 to 12 months, with periodic assessment and monitoring (AUA/CUA/SUFU [Anger 2019]; Hooton 2019c; 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).

Continuous prophylaxis:

Nitrofurantoin monohydrate/macrocrystals (Macrobid) (off-label use): Oral: 100 mg once daily at bedtime (AUA/CUA/SUFU [Anger 2019]; 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 (AUA/CUA/SUFU [Anger 2019]; 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 (AUA/CUA/SUFU [Anger 2019]; Pfau 1983; Sen 2008).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

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

Dosing: Pediatric

Urinary tract infection (UTI), treatment:

Furadantin, Macrodantin: Infants, Children, and Adolescents: Oral: 5 to 7 mg/kg/day divided every 6 hours for 7 days or at least 3 days after obtaining sterile urine; maximum dose: 100 mg/dose

Fixed dosing: Furadantin oral suspension: Oral:

7 to <12 kg: 12.5 mg every 6 hours

12 to < 22 kg: 25 mg every 6 hours

22 to <31 kg: 37.5 mg every 6 hours

31 to <42 kg: 50 mg every 6 hours

≥42 kg: 50 to 100 mg every 6 hours

Macrobid (macrocrystal/monohydrate): Adolescents: Oral: 100 mg every 12 hours for 7 days

UTI, prophylaxis: Furadantin, Macrodantin: Infants, Children, and Adolescents: Oral: 1 to 2 mg/kg/day in a single dose (at bedtime) or divided twice daily; maximum daily dose: 100 mg/day. Note: In infants and children <24 months, prophylaxis should only be considered for those with grade III-V reflux or with recurrent febrile UTI; data supporting the routine use of continuous antimicrobial prophylaxis is limited (AAP 2016; AAP [Finnell 2011])

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Administer with meals to improve absorption and decrease adverse effects; suspension may be mixed with water, milk, or fruit juice. Shake suspension well before use. The monohydrate/macrocrystals capsules (twice-daily formulation [Macrobid]) should not be opened; the macrocrystals capsules (4-times-daily formulation [Macrodantin]) may be opened and the contents mixed with food or juice for immediate use (data on file from manufacturer).

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. 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

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. 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. 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

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Consider therapy modification

Test Interactions

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

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Central nervous system: Headache (6%)

Endocrine & metabolic: Increased serum phosphate (1% to 5%)

Gastrointestinal: Nausea (8%), flatulence (2%)

Hematologic & oncologic: Decreased hemoglobin (1% to 5%), eosinophilia (1% to 5%)

Hepatic: Increased serum alanine aminotransferase (1% to 5%), increased serum aspartate aminotransferase (1% to 5%)

Frequency not defined:

Cardiovascular: Bundle branch block, chest pain, ECG changes, nonspecific T wave on ECG, vasculitis

Central nervous system: Bulging fontanel (infants), confusion, depression, drug fever, peripheral neuropathy, pseudotumor cerebri, psychotic reaction, vertigo

Dermatologic: Eczematous rash, erythema multiforme, erythematous maculopapular rash, exfoliative dermatitis, maculopapular rash, skin rash, Stevens-Johnson syndrome

Gastrointestinal: Anorexia, clostridioides, Clostridium difficile colitis, pancreatitis, sialadenitis, vomiting

Genitourinary: Urine discoloration

Hematologic & oncologic: Agranulocytosis, aplastic anemia, glucose-6-phosphate dehydrogenase deficiency anemia, granulocytopenia, hemolytic anemia, leukopenia, megaloblastic anemia, methemoglobinemia, thrombocytopenia

Hepatic: Cholestatic jaundice, chronic active hepatitis, hepatic necrosis, hepatitis

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Infection: Superinfection

Neuromuscular & skeletal: Arthralgia, asthenia, lupus-like syndrome, myalgia

Ophthalmic: Nystagmus

Respiratory: Acute pulmonary reaction, chronic pulmonary reaction, cough, cyanosis, dyspnea, dyspnea on exertion, interstitial pneumonitis, pleural effusion, pulmonary fibrosis, pulmonary infiltrates

<1%, postmarketing, and/or case reports: Abdominal pain, alopecia, amblyopia, chills, constipation, diarrhea, dizziness, drowsiness, dyspepsia, fever, hepatotoxicity, malaise, optic neuritis, pruritus, pulmonary hypersensitivity, urticaria

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 post antibiotic 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 urinary tract infection (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 2019]).

Concurrent drug therapy issues:

• 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

Reproductive Considerations

Nitrofurantoin in doses >10 mg/kg/day may cause spermatogenic arrest and decrease sperm count. This was observed in some males treated for 2 weeks; sperm counts returned to normal between 13 and 32 weeks after therapy was discontinued. Consider avoiding use in patients planning to father a child (Drobnis 2017).

Pregnancy Risk Factor

B (contraindicated at term)

Pregnancy Considerations

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 2017). An increased risk of neonatal jaundice was observed following maternal nitrofurantoin use during the last 30 days of pregnancy (Nordeng 2013).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of nitrofurantoin may be altered. Based on a study of 30 women administered nitrofurantoin prior to abortion, maternal serum concentrations of nitrofurantoin may be decreased and urine concentrations may be increased during pregnancy (Philipson 1979).

Nitrofurantoin may be used to treat infections in pregnant women when appropriate, including asymptomatic bacteriuria in pregnancy (ACOG 2017; IDSA [Nicolle 2019]). Use during the first trimester should be limited to situations where no alternative therapies are available. Use as a first-line agent in the second and third trimesters can be considered for the treatment and prevention of urinary tract infections and other confirmed infections caused by susceptible organisms. Prescriptions should be written when clinically appropriate and for the shortest effective duration for confirmed infections (ACOG 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. Alternative antibiotics should be used in pregnant patients with G-6-PD deficiency (ACOG 2017; Nordeng 2013).

Patient Education

What is this drug used for?

• It is used to treat or prevent a urinary tract infection (UTI).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Nausea

• Vomiting

• Diarrhea

• Lack of appetite

• Abdominal pain

• Dizziness

• Fatigue

• Hair loss

• Urine discoloration

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Nerve problems like sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain, or weakness in the arms, hands, legs, or feet

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting

• Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs

• Involuntary eye movements

• Severe loss of strength and energy

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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

Frequently Asked Questions