What to do when liver enzymes are elevated due to nitrofurantoin (antibiotic) use?

From the Guidelines

If you have elevated liver enzymes due to nitrofurantoin use, you should stop taking the medication immediately and contact your healthcare provider. According to the most recent guidelines, nitrofurantoin-induced liver injury typically resolves once the medication is discontinued, with liver enzymes usually returning to normal within days to weeks 1. Your doctor may recommend alternative antibiotics such as trimethoprim-sulfamethoxazole, ciprofloxacin, or amoxicillin depending on your infection and sensitivity patterns, as evidenced by studies showing similar clinical cure rates with these medications 1. During recovery, avoid alcohol and other medications that could stress the liver. Your doctor will likely order follow-up liver function tests to monitor improvement. Nitrofurantoin can cause liver injury through an immune-mediated hypersensitivity reaction or direct toxicity, particularly with long-term use. Symptoms of liver injury may include fatigue, nausea, abdominal pain, jaundice, or dark urine. In severe cases, hospitalization may be necessary for monitoring and supportive care. People with pre-existing liver disease or those over 65 years old should use nitrofurantoin with caution as they face higher risks of liver complications.

Key Considerations

• The severity of abnormal aminotransferase can be classified as mild, moderate, or severe, with moderate and severe cases requiring closer monitoring 1
• Pathologically increased levels of ALP may occur in cholestatic liver disease, which can show elevated ALP with or without elevated bilirubin 1
• Alternative antibiotics should be chosen based on the patient's infection and sensitivity patterns, as well as their medical history and potential risk factors for liver disease 1

Monitoring and Follow-up

• Follow-up liver function tests should be ordered to monitor improvement and adjust treatment as needed 1
• Patients should be advised to avoid alcohol and other medications that could stress the liver during recovery
• In severe cases, hospitalization may be necessary for monitoring and supportive care

From the FDA Drug Label

Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. Fatalities have been reported The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.

Key Points:

• Hepatic reactions, including hepatitis, can occur with nitrofurantoin use.
• If liver enzymes are elevated due to nitrofurantoin, the drug should be withdrawn immediately.
• Appropriate measures should be taken after withdrawing the drug. 2

From the Research

Elevated Liver Enzymes due to Nitrofurantoin Use

• Nitrofurantoin is a commonly prescribed antibiotic for uncomplicated urinary tract infections, but it can cause idiosyncratic drug-induced liver toxicity, presenting with abdominal pain and elevated liver enzymes 3.
• The mechanism of toxicity remains unclear, but it is hypothesized to be an autoimmune process in which steroids may play a role in treatment 4.
• Diagnosis is one of exclusion as the only definitive method of diagnosis is rechallenge 4.

Management of Elevated Liver Enzymes

• Discontinuation of nitrofurantoin is essential in managing elevated liver enzymes caused by the drug 4, 5.
• Corticosteroids have been used along with nitrofurantoin discontinuation in severe cases, but their utility has not been proven and should be used judiciously 5.
• Clinicians should be aware of the risk of developing nitrofurantoin-induced autoimmune-like hepatitis, especially in patients who have taken the drug for a long term 6.

Risk Factors and Patient Characteristics

• Prolonged exposure to nitrofurantoin, female sex, advanced age, and reduced renal function may increase the risk of developing hepatotoxicity 5.
• The majority of patients with nitrofurantoin-induced liver injury are women, with a mean age of 61 years 6.
• Hepatocellular damage is the most frequent pattern of liver injury, and nearly half of the patients may have an asymptomatic presentation 6.