What are the contraindications for Nitrofurantoin (antibiotic)?

Contraindications for Nitrofurantoin

Nitrofurantoin is absolutely contraindicated in patients with creatinine clearance <60 mL/min, pregnant women at term, neonates, and infants under 4 months of age. 1, 2

Absolute Contraindications

Renal Insufficiency

• Do not use nitrofurantoin when creatinine clearance is <60 mL/min due to inadequate urinary drug concentrations and significantly increased risk of toxicity 1
• The drug fails to achieve therapeutic levels in urine when renal function is impaired, rendering it ineffective while toxicity risk escalates 3
• Peripheral neuropathy risk increases substantially in renal impairment, and this adverse effect may become severe or irreversible 2

Pregnancy and Neonatal Considerations

• Nitrofurantoin is contraindicated in pregnant women at term (38-42 weeks gestation) 2
• Absolutely contraindicated in neonates due to risk of hemolytic anemia 2
• Avoid in infants under 4 months of age because of hemolytic anemia risk 4

Relative Contraindications and High-Risk Populations

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

• Nitrofurantoin carries a warning for patients with G6PD deficiency due to risk of hemolytic anemia 2, 5
• However, recent evidence suggests the absolute risk is low: only 42 confirmed cases of hemolysis in G6PD-deficient individuals out of at least 245 million exposures (0.00002%) 5
• For short 3-5 day courses at 200 mg total daily dose, the drug may be used without G6PD screening when accompanied by appropriate counseling, though caution is warranted 5

Conditions Increasing Peripheral Neuropathy Risk

Nitrofurantoin should be avoided or used with extreme caution in patients with: 2

• Anemia
• Diabetes mellitus
• Electrolyte imbalance
• Vitamin B deficiency
• Debilitating diseases

These conditions substantially increase the risk of severe or irreversible peripheral neuropathy.

Hepatic Disease

• Use with extreme caution in patients with underlying liver disease 6, 7
• Nitrofurantoin can cause acute hepatitis, chronic active hepatitis, cholestatic jaundice, hepatic necrosis, and cirrhosis 2, 6
• Hepatotoxicity risk is 0.0003% overall, but increases with prolonged exposure, female sex, advanced age, and reduced renal function 1, 6

Critical Clinical Pitfalls

Bacteremia and Systemic Infections

• Never use nitrofurantoin when bacteremia is suspected or present 3
• The drug does not achieve therapeutic serum concentrations when given orally, making it ineffective for systemic infections 3
• Nitrofurantoin is strictly a urinary tract-specific antibiotic 3

Chronic Kidney Disease Patients on Dialysis

• Nitrofurantoin should be avoided entirely in dialysis patients 4
• The drug can produce toxic metabolites that cause peripheral neuritis in the setting of renal failure 4
• Aminoglycosides, tetracyclines, and nitrofurantoin are specifically listed as nephrotoxic agents to avoid in chronic kidney disease 4

Age Considerations

• While patients of all ages can theoretically receive nitrofurantoin prophylaxis, elderly patients require heightened monitoring due to age-related decline in renal function 1
• Dosing must account for creatinine clearance, which naturally declines with age 2

Monitoring Requirements

When nitrofurantoin must be used in higher-risk patients (though still above the contraindication thresholds), monitor for: 2

• Signs of peripheral neuropathy (numbness, tingling, weakness)
• Pulmonary symptoms (fever, cough, dyspnea, chest pain) - pulmonary toxicity risk is 0.001% 1
• Hepatic symptoms (jaundice, right upper quadrant pain, dark urine)
• Hemolytic anemia signs (fatigue, pallor, jaundice)