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Nitrofurantoin: Drug information

Nitrofurantoin: Drug information
(For additional information see "Nitrofurantoin: Patient drug information" and see "Nitrofurantoin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Furadantin [DSC];
  • Macrobid;
  • Macrodantin
Brand Names: Canada
  • Auro-Nitrofurantoin;
  • Macrobid [DSC];
  • PMS-Nitrofurantoin BID;
  • TEVA-Nitrofurantoin
Pharmacologic Category
  • Antibiotic, Miscellaneous
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.

Asymptomatic bacteriuria in pregnancy

Asymptomatic bacteriuria (≥105 CFU per mL) in pregnancy:

Note: 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 due to the possibility of hemolytic anemia in the newborn (manufacturer’s labeling). Information from studies evaluating the risk of congenital anomalies following first trimester exposure is inconclusive (Goldberg 2015).

Nitrofurantoin monohydrate/macrocrystals (Macrobid): Oral: 100 mg twice daily for 4 to 7 days (IDSA [Nicolle 2019]; Kazemier 2015; Lumbiganon 2009).

Cystitis, acute uncomplicated or acute simple cystitis, treatment

Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without 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 2021a; Hooton 2021b; IDSA/ESCMID [Gupta 2011]).

Nitrofurantoin monohydrate/macrocrystals (Macrobid): Oral: 100 mg twice daily; treat females for 5 days and males for 7 days (Gupta 2007; Hooton 2021b; IDSA/ESCMID [Gupta 2011]).

Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Oral: 50 to 100 mg every 6 hours; treat females for 5 days and males for 7 days (Gupta 2007; Hooton 2021b; IDSA/ESCMID [Gupta 2011]). 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, prophylaxis for recurrent infection

Cystitis, prophylaxis for recurrent infection:

Note: May be considered in nonpregnant women with bothersome, frequently recurrent cystitis despite nonantimicrobial preventive measures. The optimal duration has not been established; duration ranges from 3 to 12 months, with periodic reassessment (AUA/CUA/SUFU [Anger 2019]; Hooton 2021c; 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: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 30 to <60 mL/minute: Although contraindicated in the manufacturer's labeling, limited data suggest nitrofurantoin is safe and effective for short-term treatment of uncomplicated acute cystitis in patients with an eGFR or CrCl 30 to 60 mL/minute (Chung 2019; Cunha 2017; Oplinger 2013; Santos 2016; Singh 2015). One retrospective cohort study reported increased risk of pulmonary adverse events in patients with eGFR <50 mL/minute (Geerts 2013).

CrCl <30 mL/minute: Avoid use (Beers Criteria [AGS 2019]), Cunha 2017).

Hemodialysis, intermittent (thrice weekly): Avoid use (Golightly 2013).

Peritoneal dialysis: Avoid use (Golightly 2013).

CRRT: Avoid use (Golightly 2013).

PIRRT (eg, sustained low-efficiency diafiltration): Avoid use (expert opinion).

Dosing: Hepatic Impairment: Adult

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.

Dosing: Pediatric

(For additional information see "Nitrofurantoin: Pediatric drug information")

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.

Dosing: Kidney Impairment: Pediatric

Infants ≥1 month, Children, and Adolescents:

CrCl ≥60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.

CrCl <60 mL/minute: Use is contraindicated.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling. Contraindicated in patients with a previous history of cholestatic jaundice or hepatic dysfunction associated with nitrofurantoin.

Dosing: Older Adult

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

Dosage Forms: US

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]) [contains methylparaben, propylparaben]

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

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Macrobid: 100 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), corn starch, edetate (edta) calcium disodium, fd&c red #40, fd&c yellow #10 (quinoline yellow)]

Generic: 50 mg, 100 mg

Tablet, Oral:

Generic: 50 mg, 100 mg

Administration: Adult

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).

Administration: Pediatric

Oral: Administer with food or milk; do not administer with antacid preparations containing magnesium trisilicate; suspension may be mixed with water, milk, fruit juice, or infant formula. Shake suspension well before use. The monohydrate/macrocrystals capsules (twice-daily formulation [eg, Macrobid]) should not be opened; the macrocrystals capsules (4-times-daily formulation [eg, Macrodantin]) may be opened and the contents mixed with food or juice for immediate use (data on file from manufacturer).

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, prophylaxis for recurrent infection: Nitrofurantoin macrocrystals (Furadantin, Macrodantin): Chronic suppression of recurrent urinary tract infection.

Medication Safety Issues
Sound alike/look alike issues:

Macrobid may be confused with microK, Nitro-Bid.

Nitrofurantoin may be confused with Neurontin, nitroglycerin.

Geriatric Patients: High-Risk Medication:

Beers Criteria: Nitrofurantoin is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potential for pulmonary toxicity, hepatotoxicity and peripheral neuropathy, particularly when given long-term; safer alternatives exist. Avoid use in patients with a CrCl less than 30 mL/minute or for long-term suppressive therapy (Beers Criteria [AGS 2019]).

Pharmacy Quality Alliance (PQA): Nitrofurantoin (when cumulative day supply is greater than 90 days) is identified as a high-risk medication in patients 65 years and older on the PQA's Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).

Pediatric patients: High-risk medication:

KIDs List: Nitrofurantoin, when used in neonates, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list; use should be avoided due to risk of hemolytic anemia (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).

Adverse Reactions (Significant): Considerations
Clostridioides difficile infection

Clostridioides difficile infection has occurred with nitrofurantoin, including Clostridioides difficile associated diarrhea and Clostridioides difficile colitis (Ref).

Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).

Risk factors:

• Antibiotic exposure (highest risk factor) (Ref)

• Type of antibiotic (Ref)

• Long durations in a hospitalization or other health care setting (recent or current) (Ref)

• Older adults (Ref)

• Immunocompromised conditions (Ref)

• A serious underlying condition (Ref)

• GI surgery/manipulation (Ref)

• Antiulcer medications (eg, proton pump inhibitors, H2 blockers) (Ref)

• Chemotherapy (Ref)

Drug-induced liver injury (DILI)

A wide range of drug-induced liver injury (DILI) has been reported with nitrofurantoin, including acute hepatitis, granulomatous reaction, cholestatic jaundice, autoimmune hepatitis, and chronic active hepatitis that may lead to hepatic cirrhosis or death (Ref). Acute liver injury is less common, usually presents with a hepatocellular pattern with or without jaundice and is commonly associated with fever and skin rash. Acute injury typically resolves with discontinuation (Ref). Chronic liver injury is more common, usually presents with autoimmune features and is associated with fatigue, weakness, dark urine, and jaundice (Ref).

Mechanism: Not well known; Oxidative free radicals may damage hepatocytes. In addition, autoimmune mechanism may contribute (Ref).

Onset: Varied; acute liver injury may vary in onset from 1 to 6 weeks of use and chronic liver injury may vary in onset from months (typically >6 months) to years of use (Ref).

Risk factors:

• Older patients (Ref)

• Females (Ref)

• Prolonged use (>6 months) (Ref)

Peripheral neuropathy

Peripheral neuropathy may occur with nitrofurantoin and typically presents as sensorimotor polyneuropathy (Ref).

Mechanism: Non–dose-related; idiosyncratic (Ref).

Risk factors:

• Older patients

• Anemia

• Debilitating disease

• Diabetes

• Electrolyte imbalance

• Kidney impairment (CrCl <60 mL/minute)

• Vitamin B deficiency

Pulmonary toxicity

Pulmonary toxicity may occur with nitrofurantoin and ranges from acute pulmonary reaction, subacute pulmonary reaction, and/or chronic pulmonary reaction (Ref).

Mechanism: Acute reactions: Non–dose-related; immunologic (Ref). Chronic reactions: Unknown. May be T-cell mediated (non–dose-related) or direct toxicity (dose-related) (Ref).

Onset: Varied; acute reactions can vary in onset from days to weeks while chronic reactions often occurs after months to years of use (Ref).

Risk factors:

• Older patients (Ref)

• Females (Ref)

• Prolonged use (>6 months) (for chronic pulmonary reactions) (Ref)

Adverse Reactions

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

1% to 10%:

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

Gastrointestinal: Flatulence (2%), nausea (8%)

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%)

Nervous system: Headache (6%)

<1%:

Dermatologic: Alopecia, pruritus, urticaria

Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia, vomiting

Nervous system: Chills, dizziness, drowsiness, malaise

Ophthalmic: Amblyopia

Respiratory: Acute pulmonary reaction (including cough, dyspnea, dyspnea on exertion, pleural effusion, pleuritic chest pain, pulmonary infiltrates)

Miscellaneous: Fever

Frequency not defined: Respiratory: Chronic pulmonary reaction (including diffuse interstitial pneumonitis, pulmonary fibrosis), subacute pulmonary reaction

Postmarketing:

Cardiovascular: Bundle branch block (Dibagh Gandorta 2017), ECG changes, nonspecific T wave on ECG, vasculitis

Dermatologic: Eczematous rash, erythema multiforme, exfoliative dermatitis, maculopapular rash, Stevens-Johnson syndrome (Davis 2018)

Endocrine & metabolic: Glucose-6-phosphate dehydrogenase deficiency anemia

Gastrointestinal: Anorexia, Clostridioides difficile associated diarrhea (Hirschhorn 1994), Clostridioides difficile colitis, pancreatitis (Mouallen 2003), sialadenitis

Hematologic & oncologic: Agranulocytosis (Roberts 2005), aplastic anemia, granulocytopenia, hemolytic anemia, leukopenia, megaloblastic anemia, methemoglobinemia, thrombocytopenia (Dibagh Gandorta 2017)

Hepatic: Autoimmune hepatitis (Sakaan 2014), cholestatic jaundice (Sakaan 2014), chronic active hepatitis (Sakaan 2014), hepatic cirrhosis (Sakaan 2014), hepatic necrosis (Sakaan 2014), hepatitis (acute) (Sakaan 2014)

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Bulging fontanel (infants), confusion, depression, idiopathic intracranial hypertension, peripheral neuropathy (Tan 2012), psychotic reaction, vertigo

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

Ophthalmic: Nystagmus disorder, optic neuritis

Respiratory: Cyanosis

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.

Warnings/Precautions

Concerns related to adverse effects:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Hemolytic anemia: Use caution in patients with G6PD deficiency; may be at increased risk for hemolytic anemia. Discontinue therapy if occurs.

• Hepatic impairment: Use is contraindicated in patients with a history of nitrofurantoin associated cholestatic jaundice or hepatic dysfunction.

• Renal impairment: Urinary nitrofurantoin concentrations are variable in patients with impaired renal function. Use with caution. 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]).

Special populations:

• Elderly: Avoid use in elderly patients.

• 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.

Warnings: Additional Pediatric Considerations

Nitrofurantoin should not be used to treat UTIs in febrile infants and young children; nitrofurantoin concentrates in the urine and does not reach therapeutic serum and possibly parenchymal concentrations making it ineffective to treat pyelonephritis or urosepsis (AAP 2011).

Metabolism/Transport Effects

None known.

Drug Interactions

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: 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. Risk X: Avoid combination

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy

Eplerenone: Nitrofurantoin may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

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

Magnesium Trisilicate: May decrease the serum concentration of Nitrofurantoin. Risk X: 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. Risk C: Monitor therapy

Norfloxacin: Nitrofurantoin may diminish the therapeutic effect of Norfloxacin. Risk X: 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. Risk C: Monitor therapy

Probenecid: May diminish the therapeutic effect of Nitrofurantoin. Probenecid may increase the serum concentration of Nitrofurantoin. Risk C: 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. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

Food Interactions

Nitrofurantoin serum concentrations may be increased if taken with food. Management: Administer with meals.

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 Considerations

Nitrofurantoin crosses the placenta (Perry 1967).

Current studies evaluating maternal use of nitrofurantoin during pregnancy and the development of congenital anomalies have had mixed results (Goldberg 2015). An increased risk of neonatal jaundice was observed following maternal nitrofurantoin use during the last 30 days of pregnancy (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 due to the possibility of hemolytic anemia in the newborn.

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 considered for the treatment of asymptomatic bacteriuria in pregnant patients when appropriate; the shortest effective course should be used (IDSA [Nicolle 2019]). Alternative antibiotics should be used in pregnant patients with G-6-PD deficiency (Nordeng 2013).

Breastfeeding Considerations

Nitrofurantoin is present in breast milk.

The relative infant dose (RID) of nitrofurantoin is 5% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 6 mg/kg/day. In general, breastfeeding is considered acceptable when the relative infant dose is <10% (Anderson 2016; Ito 2000).

The RID of nitrofurantoin was calculated using a milk concentration of 2.2 mcg/mL, providing an estimated daily infant dose via breast milk of 0.3 mg/kg/day. This milk concentration was obtained 3 hours following the fourth maternal dose of oral nitrofurantoin 100 mg (Pons 1990).

Adverse effects observed in case reports include diarrhea in 2 breastfeeding infants and decreased milk volume as reported by 1 mother (dose, duration, relationship to breastfeeding not provided) (Ito 1993). In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances (WHO 2002).

The therapeutic use of nitrofurantoin is contraindicated in neonates (<1 month of age) due to the possibility of hemolytic anemia caused by immature erythrocyte enzyme systems. Theoretically, this risk is also present in breastfeeding neonates exposed to nitrofurantoin via breast milk; however, no reports of hemolytic anemia in a breastfeeding neonate exposed to nitrofurantoin via breast milk have been located (Zao 2014). Nevertheless, when breastfeeding infants <1 month of age, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother. In addition, the World Health Organization states that nitrofurantoin is compatible with breastfeeding for healthy full-term infants with monitoring for adverse reactions (eg, jaundice, hemolysis). However, patients taking nitrofurantoin should avoid breastfeeding premature neonates or neonates <1 month of age (WHO 2002).

Avoidance of breastfeeding should also be considered in infants of any age where absolute or relative G-6-PD deficiency may be present (eg, Eastern Mediterranean, African, and Southeast Asian populations) due to the risk of hemolytic anemia (WHO 2002; Zao 2014).

Dietary Considerations

Take with meals to improve absorption and decrease adverse effects.

Monitoring Parameters

Signs or symptoms of pulmonary reaction (eg, malaise, dyspnea, cough, fever, radiologic evidence of diffuse interstitial pneumonitis or fibrosis); signs of numbness or tingling of the extremities; CBC, periodic LFTs, periodic renal function tests with long-term use.

Mechanism of Action

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.

Pharmacokinetics

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

Distribution: Vd: 0.8 L/kg

Protein binding: 60% to 90%

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

Bioavailability: Increased with food by ~40%

Half-life elimination: 20 to 60 minutes; prolonged with renal impairment

Excretion:

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

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

Pharmacokinetics: Additional Considerations

Renal function impairment: Nitrofurantoin accumulates in serum.

Pricing: US

Capsules (Macrobid Oral)

100 mg (per each): $7.14

Capsules (Macrodantin Oral)

25 mg (per each): $14.06

50 mg (per each): $3.15

100 mg (per each): $6.62

Capsules (Nitrofurantoin Macrocrystal Oral)

25 mg (per each): $7.03 - $12.64

50 mg (per each): $2.13 - $2.43

100 mg (per each): $2.77 - $3.53

Capsules (Nitrofurantoin Monohyd Macro Oral)

100 mg (per each): $1.69 - $5.93

Suspension (Nitrofurantoin Oral)

25 mg/5 mL (per mL): $3.18 - $14.61

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Colifuran (EG);
  • Furadantin (AT, BB, IE, IN, IS, MT, NO, SE, SI);
  • Furadantin Retard (CH);
  • Furadantina (AR, CL, MX);
  • Furadantine (FR, LU);
  • Furadantine MC (BE);
  • Furadantine-MC (NL, PT);
  • Furadin (PK);
  • Furadina (VE);
  • Furadonin (UA);
  • Furadonins (LT, LV);
  • Furanpur (UY);
  • Furantoina (ES);
  • Furitex (CR, DO, GT, HN, NI, PA, SV);
  • Furolin (GR);
  • Macrobid (GB, IE);
  • Macrodantin (AU, BB, CY, IE, IT, MT, PH, TR, ZA);
  • Macrodantina (BR, CL, CO, CR, DO, GT, HN, MX, NI, PA, PE, SV);
  • Macrodantina XR (EC);
  • Macrodin (CY);
  • Macrofuran (ID);
  • Mepafuran (EG);
  • Nifuran (NZ);
  • Nifurantin (CZ);
  • Nifuryl (EC);
  • Nifutoin (TW);
  • Nintoin (BD);
  • Ninur (HR);
  • Nitrofurantoin ”Dak” (DK);
  • Nitrofurantoin-ratiopharm (LU);
  • Orafuran (BG);
  • Piyeloseptyl (TR);
  • Rantoin (BD);
  • Siraliden (PL);
  • Urantoin (EC, ZW);
  • Uro-Tablinen (DE);
  • Urobak (BD);
  • Urocure (BD);
  • Urofuran (FI);
  • Uroin (KR);
  • Urontin (PH);
  • Urotoina (PY);
  • Uvamin (CR, DO, GT, HN, NI, PA, SV);
  • Uvamin Retard (AE, CH, EG, KW, LB, LV, QA, SA, TT);
  • Yumenin (TW)


For country abbreviations used in Lexicomp (show table)
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