Long-term nitrofurantoin: an analysis of complication awareness, monitoring, and pulmonary injury cases

Abstract

BackgroundLong-term nitrofurantoin (NF) treatment can result in pulmonary and hepatic injury. Current guidelines do not outline the type or frequency of monitoring required for detection of these injuries.AimsTo assess (1) awareness of NF complications among prescribers, (2) monitoring practice and (3) to describe the pulmonary sequelae of NF-related complications.Methods(1) Electronic questionnaire to prescribers, interrogating prescribing/monitoring practices and awareness of complications; (2) Case-note review (June-July 2020) of NF monitoring among general practitioners (GPs) in our local clinical commissioning group; (3) Case review of patients diagnosed with nitrofurantoin-induced interstitial lung disease (NFILD) at our interstitial lung disease (ILD) centre (2014-2020).Results125 prescribers of long-term NF responded to the questionnaire (82% GPs; 12% urologists). Many were unaware of the potential for liver (42%) and lung (28%) complications. 41% and 53% never monitored for these, respectively. Only 53% of urologists believed themselves responsible for arranging monitoring, whilst nearly all GPs believed this to be the prescriber’s responsibility (94%). One third of all respondents considered current British National Formulary (BNF) guidelines “not at all sufficient/clear”, with mean clarity scoring of 2.2/5. Amongst NFILD patients (n=46), NF had been prescribed most often (70%) for treatment of recurrent UTI and 59% (n=27) were prescribed for >6 months. Upon withdrawal of the medication 61% displayed resolution (completely/minimal fibrosis), whilst 16% of patients had progressive lung fibrosis.ConclusionNF can cause marked or irreversible lung complications and there is currently a shortfall in awareness and monitoring. Existing monitoring guidelines should be augmented.

Pulmonary adverse reaction caused by furazolidone: A report of two cases and literature review

“…Because of the similar energy required for reduction, all nitrofurantoins can be reduced to type I or type II nitrofurantoins, wherein reactive and carcinogenic hydroxylamine is produced; the reactive oxygen species produced by the redox cycle during type II nitro reduction has pharmacological effects. One study reported reduced lung tissue damage when nitrofurantoin and antioxidants were used together, compared to when nitrofurantoin was used alone [10]. The study suggests that oxidation is responsible for pulmonary toxicity.…”

Awareness of long-term nitrofurantoin adverse effects

“…This study evaluated clinicians’ awareness of the long-term complications of nitrofurantoin and their approach to monitoring for nitrofurantoin’s adverse effects 1. A questionnaire assessing prescribing and monitoring practices and awareness of potential complications with nitrofurantoin, including use of guidelines was sent to 675 general practitioners (GPs) and 130 urologists.…”

“…Many prescribers were unaware of the potential for hepatotoxicity (42%) or lung toxicity (28%) and more than half (53%) did not measure baseline lung or liver function 1. The most common baseline test was liver function (33%) and baseline respiratory symptoms were recorded by 21%.…”

“…The analysis of monitoring practices found that baseline monitoring was absent in 74% of the 265 patients who received long-term nitrofurantoin (54% aged >60 years; 82% women) within the previous 2 years 1. Baseline monitoring of liver function occurred in 12%, baseline monitoring of lung function occurred in 10% and baseline monitoring of both liver and lung functions occurred in 5%.…”

“…A study of long-term nitrofurantoin prescribing practices found that many prescribers did not routinely monitor for liver or pulmonary adverse events 1…”