Nitrofurantoin Use in Patients with Hepatitis
Nitrofurantoin should generally be avoided in patients with hepatitis due to the risk of drug-induced liver injury that can worsen existing hepatic disease and lead to serious complications including cirrhosis and death. 1
Mechanism of Hepatotoxicity
Nitrofurantoin can cause several patterns of liver injury:
- Acute hepatitis with elevated transaminases
- Chronic active hepatitis (immune-mediated)
- Granulomatous reactions
- Cholestatic injury
- Autoimmune-like hepatitis
The hepatotoxicity is believed to be primarily immune-mediated, as evidenced by:
- Presence of autoantibodies (ANA, SMA)
- Elevated immunoglobulins
- Histological features similar to autoimmune hepatitis 2
Risk Assessment
The risk of nitrofurantoin-induced hepatotoxicity is increased in:
- Patients with pre-existing liver disease
- Female patients
- Elderly patients
- Patients with reduced renal function
- Long-term nitrofurantoin use 3
Clinical Evidence
The British Society of Gastroenterology (BSG) guidelines specifically note that nitrofurantoin has been associated with drug-induced autoimmune hepatitis. In a study of 261 patients with autoimmune hepatitis, 9% were associated with drug ingestion, with nitrofurantoin being one of the most common culprits 1.
Case reports have documented severe chronic active hepatitis due to nitrofurantoin that can lead to cirrhosis and death. In some cases, discontinuation of the drug did not lead to remission, and glucocorticoids had to be administered 4.
Monitoring Recommendations
If nitrofurantoin must be used in a patient with stable hepatic disease (which is generally not recommended):
- Monitor liver function tests monthly and when symptoms occur 1
- Consider monitoring antinuclear antibody, anti-smooth muscle antibody, serum immunoglobulin, and hepatic panel every three months 2
- Discontinue immediately if there is evidence of worsening liver function
Alternative Approaches
For patients with hepatitis who require treatment for urinary tract infections:
- Consider alternative antibiotics with less hepatotoxic potential
- If nitrofurantoin is absolutely necessary, use for the shortest duration possible
- Avoid using nitrofurantoin for prophylaxis in patients with hepatitis
Warning Signs
Discontinue nitrofurantoin immediately and seek medical attention if any of the following occur:
- Abdominal pain
- Nausea or vomiting
- Jaundice
- Fatigue or malaise
- Elevated liver enzymes
- Elevated bilirubin
Conclusion
Given the potential for serious hepatotoxicity, including immune-mediated chronic active hepatitis that may not resolve with drug discontinuation alone, nitrofurantoin should generally be avoided in patients with pre-existing hepatitis. The risk of worsening liver disease and potential progression to cirrhosis outweighs the benefits, especially when alternative antibiotics are available for treating urinary tract infections.