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Pronunciation
(nye troe fyoor AN toyn)
Generic Available (U.S.)
Yes: Excludes suspension
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Prevention and treatment of urinary tract infections caused by susceptible strains of E. coli, S. aureus, Enterococcus, Klebsiella, and Enterobacter
Pregnancy Risk Factor
B (contraindicated at term)
Pregnancy Considerations
Because adverse effects have not been observed in animals, nitrofurantoin is classified pregnancy category B. Nitrofurantoin crosses the placenta, but very little reaches the amniotic fluid. Most published experiences with nitrofurantoin use during pregnancy have failed to identify any increased obstetric or teratogenic risks. Isolated reports of a potential increased risk for cardiovascular defects and a case report of upper limb paralysis have not been replicated in other studies. Use of nitrofurantoin during pregnancy has been generally well tolerated with rare reports of maternal toxicity including severe pulmonary reactions or hematologic adverse effects. 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.
Lactation
Enters breast milk/not recommended (infants <1 month); AAP rates “compatible” (AAP 2001 update pending)
Breast-Feeding Considerations
Minimal, if any, nitrofurantoin distributes to human milk. Use of nitrofurantoin during breast-feeding is not recommended by the manufacturer. Use with caution in patients at risk for G6PD deficiency or in newborns at risk for hyperbilirubinemia. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to nitrofurantoin or any component of the formulation; significant renal impairment (anuria, oliguria, significantly elevated serum creatinine, or Clcr <60 mL/minute); infants <1 month (due to the possibility of hemolytic anemia); pregnancy at term (38-42 weeks gestation), during labor and delivery, or when the onset of labor is imminent; use in patients with a history of cholestatic jaundice or hepatic impairment with previous nitrofurantoin therapy
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.
• Peripheral neuropathy: Has been associated with peripheral neuropathy (rare); risk may be increased in patients with anemia, renal impairment, 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: Therapeutic concentrations are not attained in urine of patients with Clcr <60 mL/minute, therefore, use is contraindicated in these patients.
Special populations:
• Elderly: Use is not recommended due to potential for renal impairment; alternative agents preferred (Beers Criteria).
• Pediatrics: 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.
Adverse Reactions
Frequency not defined.
Cardiovascular: Cyanosis, ECG changes (nonspecific ST/T wave changes, bundle branch block)
Central nervous system: Bulging fontanels (infants), chills, confusion, depression, dizziness, drowsiness, fever, headache, malaise, pseudotumor cerebri, psychotic reaction, vertigo
Dermatologic: Alopecia, angioedema, erythema multiforme, exfoliative dermatitis, pruritus, rash (eczematous, erythematous, maculopapular), Stevens-Johnson syndrome, urticaria
Endocrine & metabolic: Hyperphosphatemia
Gastrointestinal: Abdominal pain, anorexia, C. difficile colitis, constipation, diarrhea, dyspepsia, flatulence, nausea, pancreatitis, pseudomembranous colitis, sialadenitis, vomiting
Genitourinary: Urine discoloration (brown)
Hematologic: Agranulocytosis, aplastic anemia, eosinophilia, glucose-6-phosphate dehydrogenase deficiency anemia, granulocytopenia, hemoglobin decreased, hemolytic anemia, leukopenia, megaloblastic anemia, thrombocytopenia
Hepatic: Hepatitis, hepatic necrosis, transaminases increased, jaundice (cholestatic)
Neuromuscular & skeletal: Arthralgia, myalgia, numbness, paresthesia, peripheral neuropathy, weakness
Ocular: Amblyopia, nystagmus, optic neuritis
Respiratory: Cough, dyspnea, pneumonitis, pulmonary fibrosis (with long-term use), pulmonary infiltration
Miscellaneous: Acute pulmonary reaction (symptoms include chills, chest pain, cough, dyspnea, fever, and eosinophilia), anaphylaxis, hypersensitivity (including acute pulmonary hypersensitivity), lupus-like syndrome, superinfections (eg, Pseudomonas or Candida)
Drug Interactions
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Magnesium Trisilicate: May decrease the serum concentration of Nitrofurantoin. Risk X: Avoid combination
Norfloxacin: Nitrofurantoin may diminish the therapeutic effect of Norfloxacin. Risk X: Avoid combination
Probenecid: May increase the serum concentration of Nitrofurantoin. Risk C: 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 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Nitrofurantoin serum concentrations may be increased if taken with food.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect oral suspension from light.
Mechanism of Action
Inhibits several bacterial enzyme systems including acetyl coenzyme A interfering with metabolism and possibly cell wall synthesis
Pharmacodynamics/Kinetics
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
Half-life elimination: 20-60 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)
Dosage
Oral:
Children >1 month:
UTI treatment (Furadantin®, Macrodantin®): 5-7 mg/kg/day in divided doses every 6 hours; maximum: 400 mg/day. Administer for 7 days or at least 3 days after obtaining sterile urine
UTI prophylaxis (Furadantin®, Macrodantin®): 1-2 mg/kg/day in divided doses every 12-24 hours; maximum: 100 mg/day
Children >12 years: UTI treatment (Macrobid®): 100 mg twice daily for 7 days
Adults:
UTI treatment:
Furadantin®, Macrodantin®: 50-100 mg/dose every 6 hours; administer for 7 days or at least 3 days after obtaining sterile urine
Macrobid®: 100 mg twice daily for 7 days
UTI prophylaxis (Furadantin®, Macrodantin®): 50-100 mg/dose at bedtime
Dosing adjustment in renal impairment: Clcr <60 mL/minute: Contraindicated
Contraindicated in hemo- and peritoneal dialysis and continuous arteriovenous or venovenous hemofiltration
Administration: 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.
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
Test Interactions
False-positive urine glucose (Benedict's and Fehling's methods); no false positives with enzymatic tests
Dietary Considerations
Take with meals to improve absorption and decrease adverse effects.
Patient Education
Take with food. Suspension may be mixed with water, milk, fruit juice, or infant formula. Shake suspension well before use. Maintain adequate hydration unless instructed to restrict fluid intake. May cause nausea, vomiting, or diarrhea. Report immediately any rash; swelling of face, tongue, mouth, or throat; or chest tightness. Report if condition being treated worsens or does not improve by the time prescription is completed.
Geriatric Considerations
Because of nitrofurantoin's decreased efficacy in patients with a Clcr <60 mL/minute and its side effect profile, it is not an antibiotic of choice for acute or prophylactic treatment of urinary tract infections in the elderly. An increased rate of severe hepatic toxicity has been suggested by postmarketing reports.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria severity: High).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness or dizziness
Mental Health: Effects on Psychiatric Treatment
Concurrent use with anticholinergic/antiparkinsonian medications may increase the absorption of nitrofurantoin
Nursing: Physical Assessment/Monitoring
Assess allergy history and renal status prior to beginning therapy.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral [macrocrystal]: 50 mg, 100 mg
Macrodantin®: 25 mg, 50 mg, 100 mg
Capsule, oral [macrocrystal/monohydrate]: 100 mg
Macrobid®: 100 mg [nitrofurantoin macrocrystal 25% and nitrofurantoin monohydrate 75%]
Suspension, oral: 25 mg/5 mL (230 mL)
Furadantin®: 25 mg/5 mL (230 mL)
Pricing: U.S. (www.drugstore.com)
Capsules (Macrobid)
100 mg (20): $83.99
Capsules (Macrodantin)
25 mg (30): $64.99
50 mg (30): $56.99
100 mg (30): $109.99
Capsules (Nitrofurantoin Macrocrystal)
50 mg (30): $50.99
100 mg (30): $75.99
Capsules (Nitrofurantoin Monohyd Macro)
100 mg (20): $65.99
Suspension (Furadantin)
25 mg/5 mL (60): $156.00
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Brendstrup L, Hjelt K, Petersen KE, et al, “Nitrofurantoin Versus Trimethoprim Prophylaxis in Recurrent Urinary Tract Infections in Children,” Acta Paediatr Scand, 1990. 79(12):1225-34.
Burgert SJ, Burke JP, and Box TD, “Reversible Nitrofurantoin-Induced Chronic Active Hepatitis and Hepatic Cirrhosis in a Patient Awaiting Liver Transplantation,” Transplantation, 1995, 59(3):448-9.
Coraggio MJ, Gross TP, and Roscelli JD, “Nitrofurantoin Toxicity in Children,” Pediatr Infect Dis J, 1989, 8(3):163-6.
D'Arcy PF, “Nitrofurantoin,” Drug Intell Clin Pharm, 1985, 19(7-8):540-7.
Penn RG and Griffin HP, “Adverse Reactions to Nitrofurantoin in the United Kingdom, Sweden, and Holland,” Br Med J (Clin Res Ed), 1982, 284(6327):1440-2.
“Practice Parameter: The Diagnosis, Treatment, and Evaluation of the Initial Urinary Tract Infection in Febrile Infants and Young Children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection,” Pediatrics, 1999, 103(4 Pt 1):843-52.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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