Can Macrobid (nitrofurantoin) be used in patients with liver disease?

Nitrofurantoin Should Be Used with Caution in Patients with Liver Disease

Nitrofurantoin (Macrobid) should be used with caution in patients with underlying liver disease due to risk of hepatotoxicity, and is contraindicated in patients with severe hepatic impairment. 1

Hepatotoxicity Risk with Nitrofurantoin

• Nitrofurantoin can cause various forms of liver injury, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, which occur rarely but can be severe and potentially fatal 1
• The FDA label specifically warns that hepatic reactions can progress to chronic active hepatitis with insidious onset, requiring careful monitoring of liver function 1
• Case reports have documented progression to end-stage liver disease requiring liver transplantation in some patients taking nitrofurantoin 2
• The spectrum of hepatotoxicity ranges from acute hepatitis to chronic active hepatitis that could lead to cirrhosis or death 3

Recommendations for Use in Liver Disease

• Nitrofurantoin should be used with caution in patients with underlying liver disease, with increased clinical and laboratory monitoring 4
• For patients with severe, unstable liver disease, alternative antibiotics with minimal hepatic metabolism should be considered instead of nitrofurantoin 4
• The risk of hepatotoxicity appears to be increased with prolonged exposure to nitrofurantoin, female sex, advanced age, and reduced renal function 3
• If nitrofurantoin must be used in a patient with liver disease, careful monitoring of liver function tests is essential 1

Monitoring Recommendations

• Baseline liver function tests should be obtained before starting nitrofurantoin in patients with liver disease 1
• For patients with underlying liver disease, liver function tests should be monitored more frequently during treatment 4
• Patients should be monitored periodically for changes in biochemical tests that would indicate liver injury, especially during long-term therapy 1
• If hepatitis occurs, nitrofurantoin should be withdrawn immediately and appropriate measures should be taken 1

Warning Signs to Monitor

• Early signs of hepatotoxicity may include elevated liver enzymes (AST, ALT), increased serum phosphorus, and jaundice 1
• Symptoms may include nausea, anorexia, abdominal pain, fatigue, jaundice, and pruritus 3
• The onset of chronic active hepatitis may be insidious and difficult to detect without laboratory monitoring 1
• Patients should be educated about reporting any symptoms suggestive of liver injury promptly 3

Additional Considerations

• Nitrofurantoin is primarily cleared by the kidneys, and renal impairment (which often accompanies advanced liver disease) increases the risk of toxicity 1
• The mechanism of hepatotoxicity is poorly understood but is believed to be the result of an immunologic process or a direct cytotoxic reaction 3
• Nitrofurantoin has also been associated with pulmonary toxicity, which can rarely occur simultaneously with hepatotoxicity 5
• The benefits of therapy must be carefully weighed against the potential risks, especially for long-term prophylactic use in high-risk patients 3

In conclusion, while nitrofurantoin can be used with caution in patients with mild to moderate liver disease with appropriate monitoring, it should be avoided in patients with severe hepatic impairment. Alternative antibiotics should be considered for patients with advanced liver disease to minimize the risk of further hepatic injury.