Can Macrobid (nitrofurantoin) increase liver enzymes?

Nitrofurantoin Can Cause Liver Enzyme Elevations

Yes, Macrobid (nitrofurantoin) can cause liver enzyme elevations and potentially serious hepatotoxicity, ranging from mild transaminase increases to severe liver injury requiring transplantation in rare cases. 1

Hepatotoxicity Risk with Nitrofurantoin

• Nitrofurantoin is associated with both acute and chronic hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, though these reactions occur rarely 1
• Fatalities related to nitrofurantoin-induced liver injury have been reported in the FDA drug label 1
• The onset of chronic active hepatitis may be insidious, requiring periodic monitoring of liver biochemical tests to detect liver injury 1
• Laboratory adverse events associated with nitrofurantoin use include increased AST (SGOT) and increased ALT (SGPT) 1

Patterns and Presentation of Liver Injury

• Hepatocellular damage is the most frequent pattern of liver injury (83% of cases) 2
• Approximately half of patients with nitrofurantoin-induced liver injury may have an asymptomatic presentation with only elevated liver enzymes 2
• Nitrofurantoin is among the drugs most commonly implicated in drug-induced liver disease according to clinical guidelines 3
• Liver injury can present with abdominal pain and elevated liver enzymes 4

Risk Factors and Mechanisms

• Prolonged exposure to nitrofurantoin increases the risk of developing hepatotoxicity 5
• Female sex, advanced age, and reduced renal function are additional risk factors for nitrofurantoin-induced liver injury 5
• The mechanism of hepatotoxicity is poorly understood but is believed to be either immunologic or a direct cytotoxic reaction 5
• Approximately 65% of patients with nitrofurantoin-induced liver injury present with positive autoantibody titers 2

Autoimmune-Like Hepatitis

• Nitrofurantoin can cause an autoimmune-like hepatitis in approximately 22% of liver injury cases 2
• Some patients with nitrofurantoin-induced autoimmune-like hepatitis may require immunosuppressive treatment to normalize liver enzymes 2
• The presence of increased antibody titers (anti-smooth muscle antibody, antinuclear antibody) may suggest chronic hepatitis 6

Severity and Outcomes

• The spectrum of liver toxicity ranges from mild enzyme elevations to severe cases requiring liver transplantation 7, 5
• In a recent study, the median time to resolution of liver injury was 81 days, with 83% of patients recovering within six months 2
• No deaths or liver transplantations were documented in a recent case series, suggesting that most cases resolve with discontinuation of the drug 2

Monitoring and Management

• If hepatitis occurs, nitrofurantoin should be withdrawn immediately and appropriate measures taken 1
• Clinical judgment needs to be exercised to determine the contribution of nitrofurantoin to liver abnormalities, especially when there may be concomitant liver disease 3
• The pattern of liver blood tests, timing of medication use relative to liver abnormality development, and clinical setting should influence decisions about discontinuing the medication 3

Combined Toxicity

• Nitrofurantoin can simultaneously cause both pulmonary fibrosis and liver injury in patients on long-term therapy 6
• After discontinuation of nitrofurantoin therapy, patients may experience full recovery without the need for additional interventions 6

Clinical Implications

• Given the potential for serious hepatotoxicity, clinicians should weigh the risks and benefits of nitrofurantoin before initiating therapy, especially for long-term prophylaxis in high-risk patients 5
• Clinicians should be vigilant in recognizing and managing liver injury associated with nitrofurantoin 5