Nitrofurantoin Monohydrate/Macrocrystals Dosing for Uncomplicated UTI
For adult patients with uncomplicated urinary tract infection and normal renal function, the recommended dose is nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days. 1, 2
Standard Dosing Regimen
The Infectious Diseases Society of America (IDSA) and European Society for Microbiology and Infectious Diseases (ESMID) recommend 100 mg orally twice daily for 5 days as the optimal duration for uncomplicated UTIs in women. 1, 2
This 5-day regimen achieves clinical cure rates of 84-90% and bacterial cure rates of 92% at early follow-up (5-9 days post-treatment), with sustained clinical cure rates of 84% at 30-day follow-up. 2
The 5-day course represents the shortest effective duration that balances efficacy with minimizing antibiotic exposure and adverse effects. 1
Alternative Duration Options
A 7-day course (100 mg twice daily) is acceptable and shows equivalent efficacy to ciprofloxacin and trimethoprim-sulfamethoxazole, with clinical cure rates of 89-93% and bacterial cure rates of 86%. 2
Avoid 3-day regimens (100 mg four times daily) due to lower efficacy, with only 88% clinical cure and 74% bacterial cure rates. 2
Critical Contraindications and Precautions
Do not use nitrofurantoin if creatinine clearance is <60 mL/min, as inadequate urinary drug concentrations prevent bactericidal activity and increase toxicity risk (including peripheral neuropathy). 2
Avoid nitrofurantoin if early pyelonephritis is suspected, as it does not achieve adequate tissue concentrations for upper tract infections. 1, 2
Do not use in men with suspected prostatitis, as nitrofurantoin does not penetrate prostatic tissue adequately. 1
Contraindicated in patients with creatinine clearance <30 mL/min due to increased risk of peripheral neuropathy and other serious toxicities. 1
Special Population Considerations
For males with uncomplicated UTI: Use 100 mg orally every 6 hours for 7-14 days (14 days recommended when prostatitis cannot be excluded), though note that clinical efficacy in males is substantially lower with a 25% failure rate versus 10-16% in females. 3
For vancomycin-resistant Enterococcus (VRE) UTIs: Use 100 mg orally four times daily. 1, 2
For children ≥12 years: Use adult dose of 100 mg twice daily. 1, 2
For children <12 years: Use 5-7 mg/kg/day divided into 4 doses (maximum 100 mg/dose) for 7 days. 1, 2
Expected Adverse Effects
The most common side effects are nausea and headache, occurring in 5.6-34% of patients depending on the study. 1, 2
Serious pulmonary and hepatic toxicity are extremely rare, occurring in 0.001% and 0.0003% of cases, respectively. 1
When to Consider Alternative First-Line Agents
If creatinine clearance is <60 mL/min: Switch to trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (if local E. coli resistance <20%) or fosfomycin 3 g single dose. 2
If pyelonephritis is suspected: Use fluoroquinolones or trimethoprim-sulfamethoxazole instead, as nitrofurantoin does not achieve adequate renal tissue concentrations. 1
Fosfomycin 3 g single dose is an alternative first-line option with slightly lower efficacy (90% vs 95% clinical cure for nitrofurantoin). 1, 2
Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days is equivalent to nitrofurantoin if local E. coli resistance is <20% and patient has no sulfa allergy. 1, 2
Important Clinical Pitfalls to Avoid
Do not extend treatment beyond 7 days unless symptoms persist, as shorter courses minimize adverse effects while maintaining efficacy. 1
Avoid using nitrofurantoin for complicated UTIs (structural/functional abnormalities, obstruction, instrumentation, pregnancy). 1
Do not use fluoroquinolones as first-line treatment due to collateral damage and resistance concerns; reserve them for more invasive infections. 2
Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients. 1