Recommended Dose of Nitrofurantoin for Acute Cystitis
For acute uncomplicated cystitis, prescribe nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days. 1, 2
Standard Dosing Regimen
Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5-7 days is the IDSA-recommended first-line regimen, with the 5-day course being optimal for balancing efficacy and minimizing adverse effects 3, 1, 2
The 5-day regimen achieves clinical cure rates of 88-93% and bacterial cure rates of 81-92%, which is equivalent to trimethoprim-sulfamethoxazole and superior to single-dose fosfomycin 3, 1, 4
A high-quality 2018 randomized trial demonstrated that 5-day nitrofurantoin resulted in 70% clinical resolution versus 58% for single-dose fosfomycin (12% absolute difference, P=0.004), confirming nitrofurantoin's superior efficacy 5
Alternative Dosing for Specific Situations
Nitrofurantoin macrocrystals 50-100 mg four times daily for 5 days is an alternative formulation recommended by European guidelines, though the twice-daily monohydrate/macrocrystal formulation is preferred for compliance 1, 2
For vancomycin-resistant Enterococcus (VRE) cystitis specifically, use 100 mg four times daily 1
Critical Contraindications
Do not use nitrofurantoin if creatinine clearance is <60 mL/min according to current FDA labeling, as inadequate urinary drug concentrations prevent bactericidal activity 4
However, emerging evidence suggests nitrofurantoin may be effective with CrCl 30-60 mL/min (69% cure rate in one study), though it should be avoided if CrCl <30 mL/min 6
Avoid nitrofurantoin if early pyelonephritis is suspected, as it does not achieve adequate tissue concentrations for upper tract infections 1
Common Side Effects to Counsel Patients About
Nausea and headache are the most common adverse effects, occurring in 5.6-34% of patients 1, 4
Rare but serious hepatotoxicity can occur even after just 5 days of treatment, presenting as acute liver injury with jaundice 7
Key Clinical Pearls
The 5-day nitrofurantoin regimen is equivalent to 3-day trimethoprim-sulfamethoxazole in both clinical and microbiological outcomes, making it an excellent fluoroquinolone-sparing option 3, 8
Nitrofurantoin maintains excellent activity against multidrug-resistant uropathogens with minimal collateral damage to normal flora, which is why guidelines prioritize it as first-line therapy 1, 2
Extended-release formulations (100 mg twice daily) and normal-release formulations (50 mg four times daily) show equivalent efficacy for uncomplicated cystitis, though extended-release may be superior in pregnancy 9