Nitrofurantoin (Macrobid) and Liver Enzyme Elevation
Yes, nitrofurantoin can cause elevation of liver enzymes, and in rare cases can lead to serious hepatotoxicity including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis. 1
Hepatotoxicity Risk and Presentation
Nitrofurantoin-induced liver injury can present in two distinct patterns:
Acute hepatotoxicity:
- Occurs within days to weeks of starting therapy
- Typically presents with hepatocellular pattern of injury
- Often accompanied by symptoms like abdominal pain, nausea, and fatigue 2
Chronic hepatotoxicity:
- More common with long-term use (>6 months)
- Can mimic autoimmune hepatitis
- May be severe and lead to liver failure or cirrhosis 3
Risk Factors
Several factors increase the risk of nitrofurantoin-induced hepatotoxicity:
- Female sex (96% of cases in one study) 3
- Advanced age (mean age 61 years in reported cases)
- Prolonged exposure (median time 175 days in one study) 3
- Reduced renal function 4
Monitoring and Management
If nitrofurantoin therapy is initiated:
- Baseline liver function tests should be obtained before starting therapy
- Monitor periodically for changes in biochemical tests that would indicate liver injury 1
- Watch for warning signs including:
- Abdominal pain, particularly in the right upper quadrant
- Nausea or vomiting
- Jaundice
- Fatigue
- Fever or rash
Clinical Course and Outcomes
The FDA label warns that hepatic reactions occur rarely but can be serious. Fatalities have been reported. 1 If hepatotoxicity occurs, the drug should be withdrawn immediately.
In a study of 23 cases:
- 83% presented with hepatocellular pattern of injury
- 52% had asymptomatic presentation (detected only by lab abnormalities)
- Median time to resolution was 81 days after discontinuation
- 83% recovered within six months
- 22% developed autoimmune-like hepatitis requiring immunosuppressive treatment 3
Important Considerations
- Immediate discontinuation is necessary if liver injury is suspected
- Monitor liver enzymes in patients on long-term therapy
- Consider alternative antibiotics for patients with pre-existing liver disease
- Be aware that some cases may require liver transplantation in severe instances 5
- Autoimmune features may be present, with 65% of patients showing positive autoantibody titers in one study 3
The risk of hepatotoxicity should be weighed against the benefits of nitrofurantoin therapy, especially when considering long-term prophylaxis in high-risk patients.