nitrofurantoin induced liver disease

Last edited 04/2023 and last reviewed 05/2023

Nitrofurantoin can rarely cause hepatic reactions, including (1)

• cholestatic jaundice,
• chronic active hepatitis,
• autoimmune hepatitis,
• and hepatic necrosis
• nitrofurantoin should be discontinued immediately if hepatitis occurs.

The onset of hepatitis may be gradual and may not have obvious symptoms at first (1)

• is important to monitor patients periodically for changes in biochemical tests that could indicate hepatic dysfunction and for clinical signs or symptoms of liver abnormality, especially in patients taking long-term nitrofurantoin

Nitrofurantoin-induced acute liver injury generally presents days to weeks after initiation of the drug (2)

• is characterized by a predominant hepatocellular enzyme elevation with possible symptoms of fever, rash, jaundice, abdominal pain, nausea, malaise, and anorexia

Chronic injury is more insidious and usually presents after 6 months of therapy (2)

• advise patients and caregivers to be vigilant for new or worsening respiratory symptoms while taking nitrofurantoin and promptly investigate any symptoms that may indicate a pulmonary adverse reaction
• pulmonary reactions may occur with short- or long-term use of nitrofurantoin, and increased vigilance for acute pulmonary reactions is required in the first week of treatment
• patients receiving long-term therapy, for example for recurrent urinary tract infections, should be closely monitored for new or worsening respiratory symptoms, especially if elderly
• immediately discontinue nitrofurantoin if new or worsening symptoms of pulmonary damage occur
• be vigilant for symptoms and signs of liver dysfunction in patients taking nitrofurantoin for any duration, but particularly with long-term use, and monitor patients periodically for signs of hepatitis and for changes in biochemical tests that would indicate hepatitis or liver injury
• use caution when prescribing nitrofurantoin in patients with pulmonary disease or hepatic dysfunction, which may mask the signs and symptoms of adverse reactions
• advise patients to read carefully the advice in the Patient Information Leaflet about symptoms of possible pulmonary and hepatic reactions and to seek medical advice if they experience these symptoms
• report suspected adverse drug reactions (ADRs) to the Yellow Card scheme

Reference:

• Drug Safety Update volume 16, issue 9: April 2023: 3.Nitrofurantoin: reminder of the risks of pulmonary and hepatic adverse drug reactions
• Luk T, Edwards BD, Bates D, Evernden C, Edwards J. Nitrofurantoin-induced liver failure: A fatal yet forgotten complication. Can Fam Physician. 2021 May;67(5):342-344. doi: 10.46747/cfp.6705342. PMID: 33980626; PMCID: PMC8115952.