Nitrofurantoin

 

1. Generic & Brand Names

• Generic: Nitrofurantoin

• Brands:

  • Macrocrystalline: Macrobid® (100mg caps), Macrodantin® (25/50/100mg caps)

  • Monohydrate: Furadantin® (oral suspension)

• Generics: Common in most markets

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2. Drug Class & Mechanism

• Class: Nitrofuran antibiotic

• Mechanism:

  • Activated by bacterial reductases → damages DNA/RNA/proteins

  • Bacteriostatic at low doses, bactericidal at high concentrations

• Spectrum:

  • Gram-negative: E. coli, Klebsiella, Enterobacter

  • Gram-positive: Enterococcus, S. saprophyticus

  • NOT for: Proteus, Pseudomonas, Serratia (produce drug-inactivating enzymes)

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3. FDA-Approved Uses

Indication	Details
Uncomplicated Cystitis	First-line for acute lower UTI
Prophylaxis	Recurrent UTI prevention (50-100mg at bedtime)

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4. Dosing Regimens

Formulation	Acute UTI Treatment	Prophylaxis
Macrocrystalline (Macrobid®)	100 mg q12h × 5-7 days	100 mg at bedtime
Monohydrate (Furadantin®)	50-100 mg q6h × 7 days	50-100 mg at bedtime
Pediatric (≥1 month)	5-7 mg/kg/day divided q6h	Not recommended

Key Administration Rules:

• Take with food/milk ↑ absorption + ↓ nausea

• Avoid antacids ↓ efficacy

• CrCl <60 mL/min: CONTRAINDICATED (↑ toxicity + subtherapeutic urine levels)

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5. Side Effects

Common (≥10%)	Serious (<1%)
Nausea/vomiting	Pulmonary Fibrosis (chronic use)
Headache	Hepatotoxicity (jaundice)
Brown urine (harmless)	Peripheral Neuropathy
Diarrhea	Hemolytic Anemia (G6PD deficiency)

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6. Black Box Warnings & Contraindications

• 🚫 Absolute Contraindications:

  • CrCl <60 mL/min

  • G6PD deficiency (risk of hemolysis)

  • Infants <1 month (risk of hemolytic anemia)

  • Pregnancy ≥38 weeks (risk of neonatal hemolysis)

• Major Warnings:

  • Pulmonary reactions: Acute (fever, cough) or chronic (fibrosis) – discontinue immediately

  • Hepatic necrosis: Monitor LFTs with long-term prophylaxis

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7. Drug Interactions

Medication	Risk	Management
Antacids	↓ Absorption	Separate by 2h
Probenecid	↓ Urinary excretion → ↑ toxicity	Avoid combo
Uricosurics	↓ Efficacy (e.g., sulfinpyrazone)	Monitor for failure

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8. Resistance Advantages

• Resistance remains <5% in E. coli (vs. >25% for TMP-SMX)

• No cross-resistance with fluoroquinolones/cephalosporins

• Ideal for:

  • Community-acquired UTIs

  • Patients allergic to β-lactams

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9. Special Populations

Group	Recommendation
Pregnancy	Category B (avoid at term)
Breastfeeding	Avoid (infant hemolysis risk)
Elderly	Check CrCl before prescribing

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10. Storage & Handling

• Capsules: 20-25°C; protect from moisture

• Suspension: Refrigerate; discard after 7 days

• Avoid heat/light (darkens drug → harmless but alarming)

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Clinical Practice Guidelines

✅ First-Line for Uncomplicated Cystitis:

• IDSA/ESCMID: 5-day nitrofurantoin = 3-day fosfomycin (cure rates 85-90%)
  ❌ Avoid For:

• Pyelonephritis (poor tissue penetration)

• Prostatitis (no prostate penetration)

• UTIs with suspected Proteus/Pseudomonas

⚠️ Renal Function Critical:

Diagram

Code

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Nitrofurantoin vs. Alternatives for UTI

Parameter	Nitrofurantoin	TMP-SMX	Fosfomycin
Resistance (E. coli)	3-5%	20-35%	1-3%
Dosing	Twice daily	Twice daily	Single dose
Renal Safety	Avoid if CrCl<60	OK down to CrCl>15	Any function
Pregnancy	Limited use	Avoid (Category D)	Safe

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Patient Counseling

1. "Take with food to prevent upset stomach."

2. "Brown urine is normal – don't panic!"

3. "Stop immediately for:

   • Shortness of breath/cough (lung issues)

   • Yellow skin/eyes (liver problems)

   • Tingling hands/feet (nerve damage)"

4. "Do NOT use if pregnant near delivery."

💡 Pro Tip: For recurrent UTIs, vaginal estrogen (postmenopausal) or cranberry proanthocyanidins may reduce recurrence when combined with prophylaxis.

Prescribing Status: First-line for uncomplicated cystitis per IDSA guidelines. Monitor for pulmonary/hepatic toxicity with long-term use.