Background
Nitrofurantoin 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 2025.1,2 Nitrofurantoin 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).3 Given its widespread use, it is important to understand the potential, and sometimes serious, risks of nitrofurantoin use.
Risks of nitrofurantoin
The main risks associated with nitrofurantoin use relate to pulmonary and hepatic adverse events; however, awareness of the potential hepatotoxicity or pulmonary toxicity and follow-up 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.5 Alongside acute phase reactions, subacute and chronic irreversible pulmonary fibrosis and hepatic reactions are associated with longer-term use over months and years. Chronic nitrofurantoin-induced 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.3 Information 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.3 However, given the risks of adverse effects, the MHRA suggests that nitrofurantoin should be used with caution in patients with known pulmonary or hepatic dysfunction.
What to tell patients on long-term nitrofurantoin
The MHRA suggests that patients should be advised to read the patient information leaflet and seek medical advice if they experience any pulmonary or hepatic reactions.
Typical presenting symptoms of pulmonary fibrosis include dry cough and exertional dyspnoea. The presentation can be insidious and mistaken for other conditions such as heart failure in an older population. Patients should be counselled and given information about specific signs and symptoms to report to their healthcare professional, such as shortness of breath, chronic cough, haemoptysis, pleuritic chest pain, or signs of jaundice.
Suspected adverse effects should be reported using the Yellow Card Scheme, a process that is simplified now that these reporting systems are integrated into most electronic record systems.
Routine monitoring
There is a lack of guidelines towards optimal monitoring, but medicolegal experts suggest that patients receiving repeat prescribing of nitrofurantoin should be monitored for hepatic complications alongside a review of respiratory symptoms on a 6-monthly basis. The MHRA suggests that patients on long-term nitrofurantoin should be ‘periodically’ monitored for changes in hepatic function and for clinical signs of liver abnormality. There are no specific monitoring guidelines around pulmonary complications of nitrofurantoin. While lung function tests may demonstrate a restrictive pattern and reduced diffusion capacity, routine lung function monitoring is likely difficult to implement in general practice given the challenge in accessing lung function testing. The Specialist Pharmacy Service recommends periodic liver function tests (LFTs) and an estimated glomerular filtration rate (eGFR) once a dose of nitrofurantoin has been established, as nitrofurantoin is contraindicated in patients with an eGFR <45 mL/min (although short courses of a few days may be used cautiously in certain patient groups) due to increased risk of toxicity as it is renally eliminated.6 Responsibility for monitoring, especially among patients with long-term prophylaxis initiated in secondary care, should be clarified if prescribing responsibilities are transferred to general practice.
In general, NICE recommends that all oral antibiotics for UTI prophylaxis are reviewed at least 6 monthly.7 Practices should consider setting up a register or regular searches to determine which patients should have regular recalls for a review assessment and monitoring. Alongside a review of the pulmonary and hepatic risks and symptoms, a review assessment for long-term nitrofurantoin treatment, which can be conducted by practice clinical pharmacists or pharmacy technicians, should aim to review how well it is acting as a prophylactic agent and consideration of which patients may benefit from alternative strategies for UTI prophylaxis. This review appointment also presents an opportunity to discuss antimicrobial resistance and general adverse effects of long-term antibiotic use such as disruption to gut flora with patients.
Alternatives to long-term antibiotic prophylaxis
Patients should be provided with education on self-help measures to reduce UTI frequency. This includes:
ensuring high fluid intake (>1.5 L/day);
in women, reviewing bladder hygiene practice, for example, wiping with toilet tissue from front to back;
in women, not disrupting the normal protective bacterial flora in the vagina by avoiding detergents in bathwater, ‘intimate’ soaps, and vaginal douching; and
in women, voiding before and after sexual intercourse.
Patients can also be counselled on trialling alternative treatments including vaginal probiotic lactobacillus alone or in combination with oral probiotics, oral D-mannose, or cranberry supplements as these are generally well tolerated with minimal side effects. NICE suggests that vaginal probiotics, D-mannose, and cranberry supplements can be considered; however, the evidence base for these treatments is weak and reports on efficacy are conflicting.7 Alternative medication options for rUTI include:
Post-coital single-dose prophylaxis if UTIs are triggered by sexual activity.
Self-start antibiotics: patients are provided with a short course of empirical antibiotics according to local policy or previous cultures. This approach involves counselling patients to initiate antibiotic course at onset of UTI symptoms immediately after producing a mid-stream urine sample. This sample can be kept in the home refrigerator until it is delivered to the primary care provider for next working day for culture and sensitivities.
Topical vaginal oestrogen in peri-and post-menopausal women, which promotes proliferation of protective vaginal commensal flora that keep pathogens at bay. This benefit is not observed with systemic oestrogen therapy.
Methenamine hippurate (Hiprex) 1 g twice daily. Hiprex is converted to formaldehyde in the acidic environment of the urinary tract, which is bactericidal. A randomised controlled trial including 240 women with rUTI showed that it was non-inferior to antibiotic prophylaxis8
Alternative prophylactic antibiotic agents include fosfomycin 3 g/week, trimethoprim 100 mg OD, or cephalexin 125 mg OD.
The NICE guideline on rUTIs includes a useful flowchart to help guide clinicians considering options for UTI prevention.9
When should patients be referred to secondary care?
All patients with rUTI should be referred to urology if they have recurrent lower UTI of unknown cause or recurrent upper UTI, or have symptoms of suspected urinary tract malignancy. Patients previously investigated for rUTI by specialist services in whom symptoms are poorly controlled or treatment is poorly tolerated should also be referred for advice or management.
Conclusions
Nitrofurantoin is a common cause of drug-induced pulmonary disease and hepatotoxicity, which can lead to severe morbidity. Awareness of these potential side effects is crucial for early detection and prompt discontinuation of the medication. Alternatives to nitrofurantoin should be considered, especially in patients with existing pulmonary or hepatic disorders.
Footnotes
Provenance Freely submitted; internally reviewed.
Competing interests Nada Khan is an Associate Editor of the BJGP. She also works as the Clinical Advisor for the Clinical Practice Research Datalink, which is part of the Medicines and Healthcare products Regulatory Agency. The other authors have declared no competing interests.
- © British Journal of General Practice 2025
References
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(2025) OpenPrescribing Search GP prescribing data, . accessed 9 Jun 2025.
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