Nitrofurantoin: Targeted Urinary Tract Infection Relief
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Synonyms
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Nitrofurantoin is a prescription antibacterial medication specifically indicated for the treatment and prophylaxis of uncomplicated urinary tract infections (UTIs) caused by susceptible strains of Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, certain strains of Klebsiella and Enterobacter species, and some strains of Citrobacter. It belongs to the nitrofuran antibiotic class and functions as a bactericidal agent through a unique mechanism of action, interfering with multiple bacterial enzyme systems. Its pharmacokinetic profile allows for high concentrations in the urine with minimal systemic absorption, making it an ideal choice for lower urinary tract infections. This article provides a comprehensive, evidence-based overview for healthcare professionals and informed patients.
Features
- Active pharmaceutical ingredient: Nitrofurantoin (available as macrocrystals or monohydrate/macrocrystals)
- Mechanism of action: Bactericidal; inhibits bacterial acetylcoenzyme A, disrupting cell wall synthesis, carbohydrate metabolism, DNA/RNA synthesis, and protein formation
- Formulations: Oral capsules (25 mg, 50 mg, 100 mg), oral suspension
- Spectrum of activity: Primarily effective against common Gram-negative and some Gram-positive uropathogens
- FDA-approved since 1953 with a well-established safety profile when used appropriately
Benefits
- Provides highly targeted therapy with minimal disruption to gut and vaginal flora compared to broad-spectrum antibiotics
- Effective first-line treatment for acute, uncomplicated cystitis with high bacterial eradication rates
- Useful for long-term prophylaxis in patients with recurrent UTIs, reducing frequency of episodes
- Low propensity for development of bacterial resistance when used for appropriate indications
- Cost-effective therapeutic option with multiple generic formulations available
Common use
Nitrofurantoin is primarily prescribed for the treatment of acute, uncomplicated urinary tract infections caused by susceptible microorganisms. It is particularly effective against E. coli, the most common uropathogen. The medication is also indicated for chronic suppressive therapy in patients with recurrent UTIs, typically at a reduced dosage. It is not appropriate for the treatment of pyelonephritis or perinephric abscesses due to inadequate tissue penetration, and should not be used for any infections outside the urinary tract. Healthcare providers should obtain appropriate cultures and susceptibility testing before initiating therapy, especially in complicated cases.
Dosage and direction
For acute uncomplicated UTIs:
- Adults: 50-100 mg orally four times daily with food or milk for 7 days (or 3 days for uncomplicated cystitis in non-pregnant women)
- Children (>12 years): 50-100 mg orally four times daily with food for 7 days
- Children (1 month to 12 years): 5-7 mg/kg/day divided into 4 doses, not to exceed 400 mg/day
For long-term prophylaxis:
- Adults: 50-100 mg orally once daily at bedtime
- Children: 1-2 mg/kg/day orally once daily at bedtime, not to exceed 100 mg/day
Administration with food or milk enhances absorption and reduces gastrointestinal upset. The macrocrystal formulation may cause less gastrointestinal distress than the microcrystalline form. Crushed tablets or opened capsules mixed with applesauce or juice may be administered to patients with difficulty swallowing, but the entire mixture must be consumed immediately.
Precautions
Nitrofurantoin should be used with caution in patients with renal impairment (creatinine clearance <60 mL/min or significantly elevated serum creatinine) due to reduced urinary excretion and increased risk of systemic toxicity, including pulmonary reactions. Hepatic function should be monitored during prolonged therapy. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at increased risk of hemolytic anemia. Peripheral neuropathy, which may become severe or irreversible, has been reported; risk factors include renal impairment, anemia, diabetes, electrolyte imbalance, vitamin B deficiency, and debilitating disease. Pulmonary reactions, including interstitial pneumonitis and pulmonary fibrosis, can occur acutely or with chronic use. Superinfections with nonsusceptible organisms, particularly fungi, may develop.
Contraindications
Nitrofurantoin is contraindicated in patients with known hypersensitivity to nitrofurantoin or other nitrofuran derivatives. It should not be used in patients with significant renal impairment (creatinine clearance <60 mL/min) due to inadequate therapeutic urinary levels and increased risk of toxicity. Administration during pregnancy at term (38-42 weeks gestation), during labor and delivery, or when the onset of labor is imminent is contraindicated due to the risk of hemolytic anemia in the neonate. The medication is contraindicated in infants under one month of age due to the risk of hemolytic anemia. It should not be used for the treatment of systemic infections or prostatitis.
Possible side effect
Common adverse reactions (≥1%) include:
- Gastrointestinal: Nausea, emesis, anorexia, abdominal pain, diarrhea
- Neurological: Headache, dizziness, drowsiness
- Pulmonary: Acute pulmonary hypersensitivity reactions (cough, chest pain, fever, chills, dyspnea, pulmonary infiltration)
- Dermatological: Maculopapular or erythematous rash, pruritus, urticaria
- Other: Discoloration of urine (brownish-yellow, harmless)
Less common but serious adverse reactions:
- Hepatic: Hepatitis, cholestatic jaundice, chronic active hepatitis
- Hematological: Megaloblastic anemia, hemolytic anemia (especially in G6PD deficiency), granulocytopenia, thrombocytopenia
- Neurological: Peripheral neuropathy (may be irreversible), optic neuritis
- Pulmonary: Chronic pulmonary reactions (diffuse interstitial pneumonitis or pulmonary fibrosis)
- Hypersensitivity: Angioedema, anaphylaxis, arthralgia, myalgia
Drug interaction
- Antacids containing magnesium trisilicate: May reduce absorption and efficacy of nitrofurantoin
- Probenecid: Contraindicated concurrently as it inhibits renal tubular secretion of nitrofurantoin, reducing urinary concentrations while increasing systemic levels and toxicity
- Uricosuric agents: May similarly inhibit renal excretion of nitrofurantoin
- Drugs with neurotoxic potential: May enhance risk of peripheral neuropathy (e.g., chloramphenicol, phenytoin)
- Oral contraceptives: Theoretical potential for reduced efficacy due to alteration of gut flora, though evidence is limited
- Sulphonylureas: Nitrofurantoin may potentiate hypoglycemic effects
Missed dose
If a dose is missed, it should be taken as soon as remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed one. For prophylactic regimens, consistency in timing is less critical than with therapeutic dosing, but maintaining a regular schedule is recommended for optimal effect.
Overdose
Symptoms of overdose may include nausea, vomiting, and gastrointestinal distress. No specific antidote exists. Management includes gastric lavage if ingestion was recent, along with supportive measures and adequate hydration to promote urinary excretion. Hemodialysis may be of limited value due to nitrofurantoin’s rapid elimination and protein binding, but may be considered in severe cases. Cases of intentional overdose have resulted in allergic pneumonitis requiring corticosteroid therapy. In the event of suspected overdose, contact a poison control center immediately.
Storage
Store at controlled room temperature (20-25°C or 68-77°F) in a tight, light-resistant container. Keep out of reach of children. Do not use after the expiration date printed on the packaging. The oral suspension should be shaken well before each use and may be stored at room temperature for up to 3 months after reconstitution. Do not freeze. Properly discard any unused medication after completion of therapy.
Disclaimer
This information is provided for educational purposes only and does not constitute medical advice. Healthcare professionals should consult official prescribing information and clinical guidelines before prescribing nitrofurantoin. Patients should not make changes to their medication regimen without consulting their healthcare provider. The efficacy and safety of nitrofurantoin may vary based on individual patient factors, bacterial susceptibility patterns, and local resistance epidemiology. Always consider the most current clinical evidence and regulatory guidance when making treatment decisions.
Reviews
Clinical studies consistently demonstrate nitrofurantoin’s efficacy for uncomplicated UTIs, with bacterial eradication rates typically exceeding 90% for susceptible organisms. A 2018 systematic review in Clinical Microbiology and Infection confirmed nitrofurantoin remains a first-line option for acute uncomplicated cystitis despite decades of use, with resistance rates remaining below 5% for E. coli in most regions. The American Urological Association’s 2019 guideline on recurrent UT recommends nitrofurantoin as a first-line prophylactic agent (Grade B evidence). Patient satisfaction surveys indicate generally good tolerability when taken with food, though gastrointestinal side effects remain the most common reason for discontinuation. Long-term safety data support its use for prophylaxis for up to 12 months in appropriate patients.