Prevention of Future Deaths reports · 2023

Frederick Le Grice

Regulation 28 report to prevent future deaths, reference 2023-0358, written 29 Sep 2023. A coroner writes one of these when an inquest reveals a risk that could cause further deaths unless something changes.

Date of report29 Sep 2023
Reference2023-0358
DeceasedFrederick Le Grice
CoronerStephen Simblet
Coroner areaEssex
CategoryHospital Death (Clinical Procedures and medical management) related deaths
Sourcejudiciary.uk record · original PDF
Responses published2

The report

Text extracted from the PDF text layer. Reproduced verbatim, including the scan's own layout.

REGULATION 28:  REPORT TO PREVENT FUTURE DEATHS 

REGULATION 28 REPORT TO PREVENT FUTURE DEATHS 

THIS REPORT IS  BEING SENT TO: 

1.  Department for Health and Social Care 
Ministerial Correspondence and  Public 
Enquiries Unit 
Department of Health and  Social Care 
39 Victoria Street 
London 
SW1H 0EU 

1 

CORONER 

I am Stephen Simblet KC,  assistant coroner, for the coroner area of Essex 

2 

CORONER'S LEGAL POWERS 

I make this report under paragraph 7,  Schedule 5,  of the Coroners and Justice Act 
2009 and  Regulations 28 and 29 of the Coroners (Investigations) Regulations 2013 . 

3 

INVESTIGATION and INQUEST 

On 29th  September 2022 I commenced an  investigation into the death of Frederick 
William LE GRICE, aged  80.  The investigation concluded at the end of the inquest 
on 29th  September 2023. The conclusion of the inquest was natural causes,  and that 
the medical causes of death were 1a) Pneumonia 1b) Interstitial Lung Disease 1c) 
Nitrofurantoin Toxicity II  Left Ventricular Systolic Dysfunction 

4 

CIRCUMSTANCES OF THE DEATH 

Frederick Le Grice suffered with  prostate problems, which as is the case,  and did in 
this case,  lead to urinary tract infections. There are two particular antibiotics used to 
treat such  infections,  Nitrofurantoin and Trimethoprim,  along with  urology support in 
hospital.  The deceased had still continued to get UTls when on trimethoprim,  so his 
general practitioner prescribed  nitrofurantoin.  That drug carries with  it a known,  but 
rare,  risk of lung damage. After using  Nitrofurantoin for a number of years,  the 
deceased began to suffer with coughing and breathlessness.  He was referred for 
specialist respiratory advice and some time later,  the respiratory consultant advised 
that he had interstitial lung disease,  and the likely cause of the problems was the 
Nitrofurantoin, and that this should  be discontinued, which it was.  The deceased died 
two years later from pneumonia, with the interstitial lung disease and the 
nitrofurantoin toxicity contributing. 

5 

CORONER'S CONCERNS 

During the course of the inquest the evidence revealed  matters giving rise to concern. 
In  my opinion there is a risk that future deaths could occur unless action  is taken.  In 
the circumstances it is my statutory duty to report to you. 

The MATIERS OF CONCERN are as follows .  -

[BRIEF SUMMARY OF MATTERS OF CONCERN] 

1 

 (1) There is a known,  albeit rare side effect of Nitrofurantoin , of it causing lung 
damage. Nevertheless,  neither the deceased himself,  nor the clinicians involved in the 
deceased's urinary care,  who due to its specialism also have a prescribing function, 
were aware of the risk of lung damage from Nitrofurantoin. 
(2) It is not very clear in the guidance to general practitioners or patients generally, 
that the patient and the treating clinicians should be particularly alert to any signs of 
coughing or breathlessness, and that if they are present, it may well suggest that 
Nitrofurantoin is causing damage to the patient's lungs. Such damage is likely to be 
irreversible. 
(3) I am concerned as to the effectiveness of the guidance and  information available: 
(i) to general practitioners and prescribers treating those using  urinary catheters and/ 
or suffering from urinary tract infections; 
(ii) clinical staff in  urology care; 
(iii)  patients themselves 
Of the danger that Nitrofurantoin might cause lung damage, and  (a) the need for all to 
be particularly vigilant as to symptoms and signs such  as coughing or difficulty in 
breathing,  and the desirability of their breathing and respiratory abilities being 
regularly  monitored when a patient is using Nitrofurantoin (b)  produces leaflets/ 
information resources to that effect. 

6 

ACTION SHOULD BE TAKEN 

In  my opinion action should  be taken to prevent future deaths and  I believe you 
[AND/OR your organisation] have the power to take such action. 

7 

YOUR RESPONSE 

You are under a duty to respond to this report within  56 days of the date of this report, 
namely by []27th  November 2023.  I,  the coroner, may extend the period. 

Your response must contain details of action taken or proposed to  be taken,  setting 
out the timetable for action . Otherwise you must explain why no action  is proposed. 

8 

COPIES and  PUBLICATION 

I have sent a copy of my report to the Chief Coroner and to the following  Interested 
Persons 
deceased was under 18)]. I have also sent it to 
useful or of interest. 

 [and to the LOCAL SAFEGUARDING BOARD (where the 

 who may find  it 

I am also under a duty to send the Chief Coroner a copy of your response. 

The Chief Coroner may  publish either or both in a complete or redacted or summary 
form . He may send a copy of this report to any person who he believes may find  it 
useful or of interest. You  may make representations to me, the coroner,  at the time of 
your response, about the release or the publication of your response by the Chief 
Coroner. 

9 

29th  September 2023 

2

Responses

2 responses published against this report on judiciary.uk. A response is a body's written reply to the coroner's concerns; publication is at the discretion of the Chief Coroner's office, so an absent response does not mean nobody replied.

Response from Department of Health and Social Care (PDF)
The Rt Hon Dame Andrea Leadsom DBE MP 
  Parliamentary Under Secretary of State for Public Health, Start for Life and Primary Care 
39 Victoria Street 
  London 
  SW1H 0EU 

Mr Stephen Simblet KC  
Assistant Coroner for the Area of Essex  
A Block 
Chelmsford County Hall 
Victoria Road  
Chelmsford  
CM1 1QH 

13 May 2024 

Dear Mr Simblet KC,  

Thank you for the Regulation 28 report to prevent future deaths of  29 September 2023 
about  the  death  of  Mr  Frederick  William  Le  Grice.  I  am  replying  as  Minister  with 
responsibility for prescribing.       

Firstly, I would like to say how saddened I was to read of the circumstances of Mr Le 
Grice’s death and I offer my sincere condolences to  his family and loved ones. The 
circumstances  your  report  describes  are  concerning  and  I  am  grateful  to  you  for 
bringing  these matters  to  my  attention.  Please  accept my  sincere apologies  for the 
significant delay  

The report raises the following concerns: 

•  There is a known, albeit rare side effect of Nitrofurantoin, of it causing lung 
damage. Nevertheless, neither the deceased himself, nor the clinicians 
involved in the deceased's urinary care, who due to its specialism also have a 
prescribing function, were aware of the risk of lung damage from 
Nitrofurantoin: 
It is not very clear in the guidance to general practitioners or patients 
generally, that the patient and the treating clinicians should be particularly 
alert to any signs of coughing or breathlessness, and that if they are present, 
it may well suggest that Nitrofurantoin is causing damage to the patient's 
lungs. Such damage is likely to be irreversible.  

• 

•  Concerns as to the effectiveness of the guidance and information available: (i) 
to general practitioners and prescribers treating those using urinary catheters 

 
 
 
 
 
 
 
 
 
 
 
  
  
 and/ or suffering from urinary tract infections; (ii) clinical staff in urology care; 
(iii) patients themselves Of the danger that Nitrofurantoin might cause lung 
damage, and (a) the need for all to be particularly vigilant as to symptoms and 
signs such as coughing or difficulty in breathing, and the desirability of their 
breathing and respiratory abilities being regularly monitored when a patient is 
using Nitrofurantoin (b) produces leaflets/ information resources to that effect. 

In preparing this response, Departmental officials have made enquiries with Medicines 
and Healthcare products Regulatory Agency (MHRA). I am also aware that you have 
received  a  full  and  comprehensive  response  from  NHS  England  who  have  worked 
closely with the MHRA on some of the key concerns. 

The  MHRA  is  an  Executive  Agency  of  the  Department  of  Health  and  Social  Care 
(DHSC)  with  responsibility  for  the  regulation  of  medicinal  products  in  the  UK.  The 
MHRA  ensures  that  medicines  are  efficacious  and  acceptably  safe,  and  that  any 
possible side effects which have been recognised to occur with use of a medicine are 
appropriately  described  in  the  authorised  product  information.  This  comprises  the 
Summary of Product Characteristics (SmPC, intended for healthcare professionals), 
labelling, and Patient Information Leaflet (PIL, provided to patients in each medicine 
pack).  The  MHRA  does  not  regulate  any  additional  sources  of  advice  healthcare 
professionals may use when prescribing medicines, such as NICE (National Institute 
for Health and Care Excellence) guidelines or any local guidance. 

As  you  have  said,  you  undertook  Mr Le  Grice’s  inquest  in  2022;  in  early  2023,  the 
MHRA  conducted  a  review  of  the  available  evidence  concerning  nitrofurantoin  and 
pulmonary adverse drug reactions. The review considered the known safety profile of 
nitrofurantoin and the information on pulmonary adverse reactions already reflected in 
the  product  information.  This  followed  a  Regulation  28  Report  to  Prevent  Future 
Deaths 
(https://www.judiciary.uk/wp-content/uploads/2022/03/Jane-Allison-
Prevention-of-future-deaths-report-2022-0071_Published.pdf). 

The  conclusion  of  this  review  was  that  the  potential  for  pulmonary  Adverse  Drug 
Reactions (ADRs) in patients taking nitrofurantoin is well established by the available 
data,  including  published  scientific  literature  and  a  small  number  of  reports  of 
nitrofurantoin and  fatal  respiratory failure  received  by  the  MHRA.  Information  about 
these  ADRs  was present  in  the  product  information  for nitrofurantoin  for healthcare 
professionals and patients prior to this MHRA review. However, the review concluded 
that the product information should be further updated, to strengthen information on 
the need to be vigilant for respiratory symptoms, and to ensure that these warnings 
are sufficiently prominent. 

As  part  of  the  review  the  MHRA  received  independent  expert  advice  from  the 
Commission  on  Human  Medicine’s  Pharmacovigilance  Expert  Advisory  Group 
(PEAG),  who  supported  the  recommendation  that  safety  information  should  be 
updated  to  raise  awareness  amongst  healthcare  professionals  and  patients  of  the 
need to be vigilant for any new breathing symptoms when taking nitrofurantoin. 

 
 
 
 Marketing  Authorisation  Holders  (MAHs)  of  nitrofurantoin  were  informed  of  the 
outcome of the review and were asked to make changes to the existing warnings in 
the product information:   

For healthcare professionals (SmPC): 

• 

• 

• 

to  add  details  about  the  signs  of  pulmonary  damage  (as  part  of  the  existing 
warning that nitrofurantoin should be discontinued if these reactions occur); 
to  highlight  that  these  ADRs  may  occur  with  either  short-term  or  long-term 
treatment; 
to  advise  that  healthcare  professionals  should  be  vigilant  for  respiratory 
symptoms  in  patients  who  have  just  started  treatment  with  nitrofurantoin 
(alongside existing advice that patients receiving long-term treatment should be 
closely monitored). 

For patients (PIL): 

• 

• 

• 

to  expand  the  existing  warnings  about  pulmonary  ADRs,  making  these  more 
prominent; 
to  highlight  that  these  ADRs  may  occur  with  either  short-term  or  long-term 
treatment; 
to advise patients to talk to their doctor if they experience symptoms that may be 
caused by pulmonary ADRs. 

To raise further awareness amongst healthcare professionals to be alert to the risks 
of  pulmonary  ADRs,  and  to  advise  healthcare  professionals  that  they  should  tell 
patients and caregivers to be vigilant for new or worsening respiratory symptoms while 
taking nitrofurantoin, the MHRA published a Drug Safety Update (DSU) bulletin in April 
2023:  https://www.gov.uk/drug-safety-update/nitrofurantoin-reminder-of-the-risks-of-
pulmonary-and-hepatic-adverse-drug-reactions.  DSU is a  monthly publication  which 
MHRA uses to communicate important medicines safety information to UK healthcare 
professionals.  

The MHRA will continue to keep the issue of nitrofurantoin and pulmonary ADRs under 
close review.  

I hope this response is helpful. Thank you for bringing these concerns to my attention.   

Best wishes, 

THE RT HON DAME ANDREA LEADSOM DBE MP
Response from NHS England (PDF)
Stephen Simplet KC 
Essex Coroner’s Service 
Essex County Council 
County Hall 
Chelmsford 
CM1 1QH 

Dear Coroner, 

National Medical Director  
NHS England  
Wellington House 
133-155 Waterloo Road  
London 
SE1 8UG 

2nd February 2024 

Re: Regulation 28 Report to Prevent Future Deaths – Frederick William Le 
Grice who died on 23 September 2022.  

Thank  you  for  your  Report  to  Prevent  Future  Deaths  (hereafter  “Report”)  dated  13 
December 2023 concerning the death of Frederick William Le Grice on 23 September 
2022. In advance of responding to the specific concerns raised in your Report, I would 
like  to  express  my  deep  condolences  to  Frederick’s  family  and  loved  ones.  NHS 
England are keen to assure the family and the coroner that the concerns raised about 
Frederick’s care have been listened to and reflected upon.  

In  your  Report  you  raised the  concerns that  there  was  a  lack  of awareness  among 
health  professionals  and  patients  as  to  the  possible  respiratory  side  effects  of 
Nitrofurantoin and of the need to be alert to signs of coughing and breathlessness in 
patients taking the drug.  

NHS England has recently undertaken considerable work to raise awareness of the 
possible  respiratory  symptoms  of  Nitrofurantoin  and  the  need  for  vigilance  of  any 
emerging symptoms, following another case where a patient developed lung disease 
following long term treatment of nitrofurantoin.  

The  National  Patient  Safety  and  Antimicrobial  Resistance  Teams  at  NHS  England 
worked closely on this issue with the Medicines and Healthcare products Regulatory 
Agency (MHRA). This has culminated in the wording in both the Summary of Product 
Characteristics  (SmPC)  and  the  Patient  Information  Leaflet  (PIL)  for  Nitrofurantoin 
being  updated  and  strengthened  to  emphasise  the  need  for  vigilance  of  emerging 
respiratory  symptoms  during  treatment  and  to  ensure  that  these  warnings  are 
prominent.  The  SmPC  is  used  by  healthcare  professionals  such  as  GPs  and 
pharmacists for guidance on how to use and prescribe a medicine and a PIL must be 
given to all patients with information on their medications when they receive them.  

Subsequently, the updates were also communicated to healthcare professionals via a 
MHRA Drug Safety Update on 26 April 2023. This work is also highlighted in an NHS 
England Patient Safety Case Study in August 2023.  

In consideration of the concerns raised in your Report, my regional colleagues in the 
East of England have been engaging with the relevant Trust to learn what actions have 

                                                                                                                       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 been  taken  in  response  to  the  concerns  raised.  The  Trust  have  advised  that  their 
Urology and Respiratory Leadership Teams have agreed to send a Patient Safety Alert 
to  the  Urology  Teams  to  advise  of  the  possible  respiratory  side  effects  of 
Nitrofurantoin.  They  will  also  be  raising  further  awareness  of  the  case  at  the  next 
Urology Divisional Audit Session.  

I would also like to provide further assurances on national NHS England work taking 
place around the Reports to Prevent Future Deaths. All reports received are discussed 
by  the  Regulation  28  Working  Group,  comprising  Regional  Medical  Directors,  and 
other clinical and quality colleagues from across the regions. This ensures that key 
learnings and insights around preventable deaths are shared across the NHS at both 
a national and regional level and helps us pay close attention to any emerging trends 
that may require further review and action.  

Thank you for bringing these important patient safety issues to my attention and please 
do not hesitate to contact me should you need any further information. 

Yours sincerely, 

National Medical Director

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