What is the recommended adult dosing of nitrofurantoin for uncomplicated urinary tract infection, including extended‑release and prophylaxis regimens, and what are its contraindications?

Nitrofurantoin Adult Dosing

Standard Dosing for Uncomplicated Cystitis in Women

For uncomplicated lower urinary tract infections in adult women, prescribe nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5 days. 1

• This 5-day regimen achieves clinical cure rates of 88-93% and bacteriological cure rates of 81-92% in women with uncomplicated UTI. 1
• The 5-day duration is optimal; extending therapy beyond 5 days does not improve outcomes and increases adverse event risk. 1
• Nitrofurantoin 100 mg twice daily for 5 days is superior to single-dose fosfomycin (70% vs 58% clinical resolution at 28 days, P=0.004). 2

Alternative Dosing Regimens

• Macrocrystalline formulation: 50-100 mg orally four times daily for 5 days. 1
• Extended-release formulation: 100 mg orally twice daily for 5 days. 1
• For VRE (vancomycin-resistant Enterococci) UTIs: 100 mg orally four times daily. 1

Dosing for Males with UTI

• For uncomplicated UTIs in males: 100 mg orally every 6 hours for 7-14 days. 3
• Treatment duration should be 14 days when prostatitis cannot be excluded. 3
• Important caveat: Clinical efficacy in males is substantially lower than in females (25% failure rate in males vs 10-16% in females), which should influence antibiotic selection. 3

Prophylaxis Dosing

• For long-term prophylaxis of recurrent UTIs: Macrocrystalline nitrofurantoin 50 mg orally at bedtime for up to 12 months. 4
• This prophylaxis regimen reduces symptomatic episodes 5.4-fold and is well-tolerated in long-term use. 4

Critical Contraindications

Nitrofurantoin is absolutely contraindicated in the following scenarios:

• Creatinine clearance <30 mL/min: Contraindicated due to inadequate urinary drug concentrations and increased risk of peripheral neuropathy. 3, 1
• Suspected or confirmed pyelonephritis: Do not use if fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting, or any systemic symptoms are present, as nitrofurantoin does not achieve adequate renal tissue concentrations. 1
• Suspected prostatitis in males: Nitrofurantoin does not penetrate prostatic tissue adequately. 1

Relative Contraindications (Use with Caution)

• CrCl 30-60 mL/min: Current guidelines vary; some recommend avoidance at CrCl <60 mL/min, though research suggests efficacy is maintained at CrCl 30-60 mL/min. 3, 5
• Pregnancy near term, labor, or delivery: Avoid due to risk of hemolytic anemia in the newborn. 1

Clinical Decision Algorithm

Step 1: Confirm uncomplicated lower UTI

• Symptoms limited to dysuria, urgency, frequency, or suprapubic discomfort WITHOUT fever, flank pain, nausea/vomiting, or costovertebral angle tenderness. 1
• Patient must be non-pregnant (or early pregnancy only), have no known urological abnormalities, and no immunosuppression. 1

Step 2: Verify renal function

• Check creatinine clearance; if CrCl <30 mL/min, choose alternative agent (trimethoprim-sulfamethoxazole or fosfomycin). 1
• If CrCl 30-60 mL/min, nitrofurantoin may still be used with close monitoring, though guidelines are evolving. 5

Step 3: Prescribe appropriate regimen

• Women with uncomplicated cystitis: 100 mg twice daily for 5 days. 1
• Men with uncomplicated UTI: 100 mg every 6 hours for 7-14 days (14 days if prostatitis cannot be excluded). 3
• Prophylaxis: 50 mg at bedtime for up to 12 months. 4

Step 4: Counsel on adverse effects

• Most common side effects are nausea (3%) and headache (1-3%), with overall adverse event rates of 5.6-34%. 1
• Serious pulmonary and hepatic toxicity are extremely rare (0.001% and 0.0003%, respectively). 1

Common Pitfalls to Avoid

• Do not prescribe for "borderline" upper-tract symptoms: Any flank pain, low-grade fever, or systemic symptoms warrants a fluoroquinolone or cephalosporin instead. 1
• Do not use empirically in males without considering lower efficacy: The 25% failure rate in males should prompt consideration of alternative agents or longer treatment duration. 3
• Do not obtain routine post-treatment urine cultures: Cultures are unnecessary for asymptomatic patients; obtain only if symptoms persist after therapy or recur within 2 weeks. 1
• Do not treat asymptomatic bacteriuria: Antibiotics should not be prescribed for asymptomatic bacteriuria in non-pregnant patients or those not undergoing urological procedures. 1
• Verify susceptibility for intrinsically resistant organisms: Nitrofurantoin is ineffective against Proteus species, Pseudomonas, and Serratia; treatment failures often occur with these organisms. 5

Special Populations

Elderly patients (>65 years):

• Standard dosing applies; older patients do not report more adverse events than younger patients. 4
• Avoid if CrCl <30 mL/min due to increased risk of peripheral neuropathy. 1

Patients with diabetes:

• Treat similarly to patients without diabetes when presenting with acute uncomplicated cystitis and no voiding abnormalities. 6

Patients with imaging abnormalities:

• Patients with structural urological abnormalities respond as well to prophylaxis as those without abnormalities. 4