Long-term nitrofurantoin use: risks and alternatives in general practice

BackgroundNitrofurantoin is a broad-spectrum antibiotic that is effective against both gram-negative and gram-positive bacteria.Although it is a fairly 'old' antibiotic, first approved by the US Food and Drug Administration in 1953, it has a minimal resistance pattern and continues to be a commonly prescribed drug, with over 3.7 million items prescribed from March 2024 to February 2025. 1,2Nitrofurantoin is typically used for short courses to treat lower urinary tract infections (UTIs); however, some patients may use it for months, or even years, as a once-daily prophylactic antibiotic for recurrent UTIs (rUTIs). 3Given its widespread use, it is important to understand the potential, and sometimes serious, risks of nitrofurantoin use. Risks of nitrofurantoinThe main risks associated with nitrofurantoin use relate to pulmonary and hepatic adverse events; however, awareness of the potential hepatotoxicity or pulmonary toxicity and followup monitoring for lung or liver-related tests is low among GPs. 4 In April 2023, the Medicines and Healthcare products Regulatory Agency (MHRA) published a Drug Safety Update to remind healthcare providers to be vigilant of new or worsening pulmonary or hepatic symptoms.This safety update was published after the death of a patient with acute pulmonary damage following a 10-day course of nitrofurantoin. 5Alongside acute phase reactions, subacute and chronic irreversible pulmonary fibrosis and hepatic reactions are associated with longer-term use over months and years.Chronic nitrofurantoininduced interstitial lung disease is thought to be a result of direct toxicity and is dose related, and therefore more common in patients taking nitrofurantoin for longer periods of time. 3nformation on the incidence and rates of adverse events is based on retrospective studies and systematic reviews.In observational, population-based cohort studies, severe nitrofurantoin toxicity is reportedly rare, with the frequency of severe adverse reactions ranging from 0.02-1.5 events per 1000 nitrofurantoin users, with prolonged use reported at 1.3 events per 1000 nitrofurantoin user. 3However, given the risks of adverse effects, the MHRA suggests that nitrofurantoin should be used with caution in patients with known pulmonary or hepatic dysfunction.