What are the side effects of nitrofurantoin?

Nitrofurantoin Side Effects

Nitrofurantoin can cause a range of side effects from common gastrointestinal disturbances to rare but serious pulmonary and hepatic toxicity, with the most concerning adverse events being pulmonary reactions, hepatotoxicity, and peripheral neuropathy. 1

Common Side Effects

• Gastrointestinal effects:

  • Nausea and vomiting (most common)
  • Anorexia
  • Abdominal pain
  • Diarrhea (less common)
  • These are dose-related and can be minimized by reducing dosage 1

• Allergic reactions:

  • Maculopapular or erythematous skin rashes
  • Pruritus
  • Urticaria
  • Drug fever
  • Hypersensitivity reactions (most frequent spontaneously-reported adverse events worldwide) 1

Serious Side Effects

Pulmonary Reactions

• Acute reactions (usually within first week of treatment):

  • Fever, chills, cough
  • Chest pain, dyspnea
  • Pulmonary infiltration with consolidation or pleural effusion on x-ray
  • Eosinophilia
  • Usually reversible with cessation of therapy 1

• Chronic reactions (with long-term use):

  • Pulmonary fibrosis
  • Interstitial pneumonitis
  • The rate of serious pulmonary adverse events is extremely low (0.001%) 2

Hepatotoxicity

• Acute hepatitis:

  • Cholestatic jaundice
  • Elevated liver enzymes
  • Abdominal pain 1

• Chronic hepatitis:

  • Can mimic autoimmune hepatitis
  • May lead to cirrhosis with continued use 3
  • The rate of serious hepatic adverse events is extremely low (0.0003%) 2
  • Can present with increased antibody titers (anti-smooth muscle antibody, antinuclear antibody) 4

Neurologic Effects

• Peripheral neuropathy:

  • Can become severe or irreversible
  • More common in patients with renal impairment, anemia, diabetes, electrolyte imbalance, or vitamin B deficiency 1

• Other neurologic effects:

  • Asthenia, vertigo, nystagmus
  • Dizziness, headache, drowsiness
  • Benign intracranial hypertension (pseudotumor cerebri) - rare
  • Confusion, depression, optic neuritis - rare 1

Hematologic Effects

• Methemoglobinemia (rare)
• Hemolytic anemia
• Agranulocytosis
• Leukopenia
• Thrombocytopenia 1

Immunologic Reactions

• Lupus-like syndrome (associated with pulmonary reactions)
• Systemic inflammatory response syndrome (rare) 5
• Drug-induced autoimmune hepatitis 6

Risk Factors for Serious Adverse Events

• Renal impairment (creatinine clearance <60 mL/minute)
• Long-term use (especially for hepatotoxicity)
• Older age
• Pre-existing pulmonary disease
• Anemia or vitamin B deficiency (for neuropathy) 1

Monitoring Recommendations

• Monitor for signs of pulmonary toxicity (cough, dyspnea, chest pain)
• Monitor liver function tests with long-term use
• Be alert for symptoms of peripheral neuropathy
• Discontinue immediately if serious adverse reactions occur 1

Special Considerations

• In drug-induced liver injury cases, nitrofurantoin was associated with 9% of cases, particularly with long-term use 2
• Complete recovery is possible after discontinuation of the drug in many cases of pulmonary and hepatic toxicity 4
• Nitrofurantoin is commonly used for UTI prophylaxis but requires careful monitoring for adverse effects 2

Clinical Pearls

• Symptoms of toxicity may not be recognized as drug-related initially and can become more severe if therapy is not stopped 1
• Simultaneous pulmonary and hepatic toxicity can occur in patients on long-term therapy 4
• Hepatotoxicity may be immune-mediated, possibly involving CD8+ T cells 7
• Resolution of adverse effects after discontinuation can be dramatic, often without requiring additional treatment 1, 4

When prescribing nitrofurantoin, carefully weigh the benefits against potential risks, particularly in patients with risk factors for serious adverse events, and ensure appropriate monitoring during treatment.