Nitrofurantoin
Pronunciation
(nye troe fyoor AN toyn)
U.S. Brand Names
Furadantin®; Macrobid®; Macrodantin®
Generic Available
Yes: Excludes suspension
Canadian Brand Names
Apo-Nitrofurantoin®; Macrobid®; Macrodantin®; Novo-Furantoin
Use
Prevention and treatment of urinary tract infections caused by susceptible gram-negative and some gram-positive organisms;
Pseudomonas
,
Serratia
, and most species of
Proteus
are generally resistant to nitrofurantoin
Pregnancy Risk Factor
B (contraindicated at term)
Pregnancy Implications
Teratogenic effects have not been observed, however, may cause hemolytic anemia in infants. Use of nitrofurantoin is contraindicated at term (38-42 weeks gestation), during labor and delivery, or when the onset of labor is imminent.
Lactation
Enters breast milk/not recommended (infants <1 month); AAP rates "compatible"
Contraindications
Hypersensitivity to nitrofurantoin or any component of the formulation; 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
Warnings/Precautions
Use with caution in patients with G6PD deficiency or in patients with anemia. Therapeutic concentrations of nitrofurantoin are not attained in urine of patients with Clcr<60 mL/minute. Use with caution if prolonged therapy is anticipated due to possible pulmonary toxicity. Acute, subacute, or chronic (usually after 6 months of therapy) pulmonary reactions have been observed in patients treated with nitrofurantoin; if these occur, discontinue therapy immediately; monitor closely for malaise, dyspnea, cough, fever, radiologic evidence of diffuse interstitial pneumonitis or fibrosis. Rare, but severe hepatic reactions have been associated with nitrofurantoin (onset may be insidious); discontinue immediately if hepatitis occurs. Has been associated with peripheral neuropathy (rare); risk may be increased by renal impairment, diabetes, vitamin B deficiency, or electrolyte imbalance; use caution.
Adverse Reactions
Frequency not defined.
Cardiovascular: Chest pain, cyanosis, ECG changes (associated with pulmonary toxicity)
Central nervous system: Chills, depression, dizziness, drowsiness, fatigue, fever, headache, pseudotumor cerebri, psychotic reaction
Dermatologic: Alopecia, erythema multiforme, exfoliative dermatitis, pruritus, rash, Stevens-Johnson syndrome
Gastrointestinal: Abdominal pain,
C. difficile
-colitis, constipation, diarrhea, dyspepsia, loss of appetite, nausea (most common), pancreatitis, sore throat, vomiting
Hematologic: Agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia, methemoglobinemia, thrombocytopenia
Hepatic: Cholestasis, hepatitis, hepatic necrosis, transaminases increased, jaundice (cholestatic)
Neuromuscular & skeletal: Arthralgia, numbness, paresthesia, peripheral neuropathy, weakness
Ocular: Amblyopia, nystagmus, optic neuritis (rare)
Respiratory: Cough, dyspnea, pneumonitis, pulmonary fibrosis
Miscellaneous: Hypersensitivity (including acute pulmonary hypersensitivity), lupus-like syndrome
Overdosage/Toxicology
Symptoms of overdose include vomiting. Treatment is supportive.
Drug Interactions
Decreased effect: Antacids, especially magnesium salts, decrease absorption of nitrofurantoin; nitrofurantoin may antagonize effects of norfloxacin
Increased toxicity: Probenecid (decreases renal excretion of nitrofurantoin); anticholinergic drugs increase absorption of nitrofurantoin
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Nitrofurantoin serum concentrations may be increased if taken with food.
Stability
Store at room temperature 15°C to 30°C (59°F to 86°F).
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; crosses placenta; enters breast milk
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: 5-7 mg/kg/day in divided doses every 6 hours; maximum: 400 mg/day
UTI prophylaxis (chronic): 1-2 mg/kg/day in divided doses every 12-24 hours; maximum: 100 mg/day
Adults: 50-100 mg/dose every 6 hours
Macrocrystal/monohydrate: 100 mg twice daily
UTI prophylaxis (chronic): 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
Administer with meals to slow the rate of absorption and decrease adverse effects; suspension may be mixed with water, milk, fruit juice, or infant formula
Monitoring Parameters
Signs of pulmonary reaction, signs of numbness or tingling of the extremities, periodic liver function tests
Test Interactions
False-positive urine glucose (Benedict's and Fehling's methods); no false positives with enzymatic tests
Patient Education
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take entire prescription, even if you are feeling better. Take with food. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. If you have diabetes, drug may cause false test results with Clinitest® urine glucose monitoring; use of another type of glucose monitoring is preferable. May cause nausea or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); or diarrhea (buttermilk, boiled milk, or yogurt may help). Report immediately and 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.
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
Dosage Forms
Capsule, macrocrystal: 50 mg, 100 mg
Macrodantin®: 25 mg, 50 mg, 100 mg
Capsule, macrocrystal/monohydrate (Macrobid®): 100 mg
Suspension, oral (Furadantin®): 25 mg/5 mL (470 mL)
References
"American Academy of Pediatrics Committee on Drugs. The 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
Apo-Nitrofurantoin® (CA, SG); Furabid® (NL); Furadantina® (AR, CL); Furadantin® (AT, CH, DE, GB, IE, IN, IT, NO, NZ, SE, ZA); Furadantine® (BE, FR, LU, NL); Furadantin Suspension® (AU); Furadoïne® (FR); Furadonin® (RU); Furantoina® (DO, ES, GT, HN, SV); Furantoin Leciva® (CZ); Furedan® (IT); Furil® (IT); Furobactina® (ES); MacroBID® (CA); Macrobid® (GB); Macrodantina® (BR, CL, CO, MX); Macrodantin® (AU, CA, GB, HK, IE, IT, ZA); Macrodin® (CY); Macrosan® (CL); Microdoïne® (FR); Neo-Furadantin® (IT); Nephrotoin® (BD); Nifuran® (NZ); Nifurantin® (CZ, DE, IL); Nifuratio® (PL); Nifuretten® (DE); Ninur® (HR); Nitrofurantoina® (CL, RO); Nitrofurantoin Agepha® (AT); Nitrofurantoina L.CH.® (CL); Nitrofurantoina Macro® (CL); Nitrofurantoin Dak® (DK); Nitrofurantoin® (GB, HU); Nitrofurantoin-ratiopharm® (DE, LU, PL); Nitrofurantoin SAD® (DK); Nitro Macro® (CL); Novo-Furantoin (CA); Piyeloseptyl® (TR); Ralodantin® (AU); Siraliden® (PL); Urantoin® (IL); Urodin® (CH); Uro Tablinen® (DE); Uvamin® (IL); Uvamin retard® (CH, CR, CY, EC, EG, GT, HN, JO, KW, LB, PA, SV)
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