GovWire

Pulmonary damage and nitrofurantoin

Nitrofurantoin is a broad-spectrum antibacterial agent, which has been available since the 1950s. It is indicated in adults, children and infants over 3 months old for:

• treatment and prophylaxis of acute or recurrent uncomplicated urinary tract infections (UTIs)
• treatment and prophylaxis of acute or recurrent uncomplicated pyelitis

The NICE guidelines on antimicrobial prescribing for UTIs recommend nitrofurantoin as one of the first choices, particularly if there is a high risk of trimethoprim resistance (for example NICE guideline 109). Treatment courses for infections are indicated to last between 3 and 7 days. However, some patients may be given a daily dose as prophylaxis for recurrent UTIs.

Reports of acute pulmonary damage

The MHRA has received a Coroners report following the death of a patient who experienced acute pulmonary damage and respiratory failure after being treated with nitrofurantoin for a UTI for a 10-day course. The Coroner raised concerns about the known risk of acute pulmonary damage following nitrofurantoin treatment and the need to highlight this to healthcare professionals and patients.

The potential for acute pulmonary damage with nitrofurantoin is well-documented in the product information for nitrofurantoin. The Summary of Product Characteristics (SmPC) states that acute, subacute and chronic pulmonary adverse reactions have been observed in patients treated with nitrofurantoin. Symptoms of acute pulmonary reactions usually include fever, chills, cough, chest pain, dyspnoea, pulmonary infiltration with consolidation or pleural effusion on chest X-ray, and eosinophilia. For subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form.

Information from published studies on the frequency or severity of pulmonary adverse drug reactions in association with acute use of nitrofurantoin is limited. A precise estimate of frequency of these pulmonary adverse drug reactions and the frequency of fatal outcomes cannot be made, but evidence from observational studies ^{[footnote 1] [footnote 2]} suggests that the pulmonary pulmonary adverse drug reactions in association with acute use of nitrofurantoin are infrequent.

If symptoms of pulmonary damage occur, nitrofurantoin should be discontinued immediately. The Patient Information Leaflet (PIL) advises patients that lung adverse reactions may occur and that patients should consult a doctor immediately if they notice symptoms of a lung reaction. Close monitoring of pulmonary conditions is advised for patients receiving long-term therapy (especially elderly people). Patients and carers should be reminded about the symptoms of pulmonary damage and the need to seek prompt medical advice if they experience these symptoms.

Following advice from the Pharmacovigilance Expert Advisory Group of the Commission on Human Medicines, Marketing Authorisation Holders for these medicines have been requested to strengthen the wording in the UK SmPC and PIL. These updates will include the advice that healthcare professionals should be vigilant for respiratory symptoms in patients taking nitrofurantoin, for any duration, and promptly investigate these symptoms, as they may indicate a pulmonary reaction.

Reminder of the risk of hepatic reactions

Following discussions with NHS England, we would like to remind healthcare professionals of the risk of hepatic adverse drug reactions and clarify our advice on the frequency of monitoring.

Nitrofurantoin can rarely cause hepatic reactions, including cholestatic jaundice, chronic active hepatitis, autoimmune hepatitis, and hepatic necrosis. Events with a fatal outcome have been reported. Nitrofurantoin should be discontinued immediately if hepatitis occurs.

The onset of hepatitis may be gradual and may not have obvious symptoms at first. It 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.

When scheduling periodic monitoring, take into account relevant local guidance, as well as any pre-existing conditions that might mask the symptoms of a hepatic reaction and the patients ability to recognise symptoms and seek advice in the event of a hepatic reaction. This periodic monitoring may be an opportunity to remind patients about the possible symptoms of hepatic reactions and to remind them to seek medical advice if they experience these symptoms.

Report any suspected adverse drug reactions

Please continue to report suspected adverse drug reactions to nitrofurantoin via the Yellow Card scheme. Your report will help us safeguard public health.

Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

• the Yellow Card website
• the Yellow Card app; download from the Apple App Store or Google Play Store
• some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)

When reporting, please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 16, issue 9: April 2023: 3.