Prevention of Future Deaths reports · 2022

Jane Allison

Regulation 28 report to prevent future deaths, reference 2022-0071, written 7 Mar 2022. A coroner writes one of these when an inquest reveals a risk that could cause further deaths unless something changes.

Date of report7 Mar 2022
Reference2022-0071
DeceasedJane Allison
CoronerCrispin Oliver
Coroner areaCounty Durham and Darlington
CategoryCommunity health care · Alcohol, drug and medication related deaths
Sourcejudiciary.uk record · original PDF
Responses published4

The report

Text recovered by OCR from a scanned PDF. OCR is imperfect: check anything you rely on against the source PDF. Reproduced verbatim, including the scan's own layout.

Regulation 28: REPORT TO PREVENT FUTURE DEATHS
NOTE: This form is to be used after an inquest.
REGULATION 28 REPORT TO PREVENT DEATHS
THIS REPORT IS BEING SENT TO:
And University Medical Group

Chief Executive, Royal Pharmaceutical Society
Chief Executive, National Institute For Heath Care Excellence

Iam Crispin OLIVER, Assistant Coroner for the coroner area of County Durham and

paragraph 7, Schedule 5, of the Coroners and Justice Act 2009
and regulations 28 and 29 of the Coroners (Investigations) Regulations 2013.

INVESTIGATION and INQUEST

On 02 December 2021 I commenced an investigation into the death of Jane Elizabeth
ALLISON aged 84. The investigation concluded at the end of the inquest on 01 March
2022. The conclusion of the inquest was that:

Died at University of North Durham on 20th November 2021. She had been admitted to the
hospital on 11th November. She had been started on the nitrofurantoin for a UTI on 28th
October. This is a conventional medication. She had a total course of 10 days. There were

telephone consultations with her GP on Sth and 10th November. She suffered side effects of
the medication but respiratory problems were not reported or noted. On 11th November
she was discovered to be suffering from catastrophic pulmonary damage.

CIRCUMSTANCES OF THE DEATH
Jane passed away in hospital after being admitted on 11th November 2021 with severe

During the course of the investigation my inquiries 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 MATTERS OF CONCERN are as follows:
(brief summary of matters of concern)

The Cause of Death was 1)3) Acute Pulmona
Hi-fi ha ee ar ag cl patie i a
was 2 narrative one, that she “died from the effects of prescribed medication”. The
following, I acknowledge: that Nitrofurantoin is a well established medication with a long
history of proven efficacy; deaths associated arising from side effects are very rare; the
drug BNF content published by NICE does include in the listed side effects pulmonary and
respiratory issues; likewise the BNF content does say that that in relation to monitoring of
therapy ..monitor for pulmonary symptoms, especially
i g function)”. All this said, Jane was aged

28 — After Inquest
Document Template Updated 30/07/2021

84. She was he was fit and active for her age, but this has the effect of
heightening my concerns, as that fact that she had no relevant co-morbidities. Also
the course of treatment of the drug in this instance was not long, being 10 days in total,
after which she died as a consequence of catastrophic pulmonary failure. Her GP, while
reporting that Jane never informed her of any breathing difficulties when she consulted with
her, also said that she had simply been following BNF content advice on this medication. In
effect, my concern is that the BNF content had not advised to be alert to the danger of
sudden pulmonary deterioration in an elderly patient, and certainly not one who was fit and
active, and not in the context of the duration of a prescribing, dispensing and
administration period of only 10 days. Effectively, the BNF content did not cover the
eventuality of this case in that it was deficient in providing advice as to monitoring and
being alert for pulmonary failure. For the avoidance of doubt, I am including the GP medical
centre as a recipient of my concerns as clinicians there may concur with them, albeit the
extent of their reaction to this death has been limited to peer group review and advice
limited to within that medical practice.

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.

YOUR RESPONSE

You are under a duty to respond to this report within 56 days of the date of this report,
namely by May 02, 2022. 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. Other action i: ed. "s
‘COPIES and PUBLICATION

I have sent 2 copy of my report to the Chief Coroner and to the following Interested
Persons

T have also sent it to
0} EE ciaypath and university Medical Group
who may find it useful or of interest.

Tam also under a duty to send a copy of your response to the Chief Coroner and all
interested persons who in my opinion should receive it.

I may also send a copy of your response to any person who I believe may find it useful or
of interest.

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.

Responses

4 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 Claypath and University Medical Group (PDF)
MM/JS/54992)

2 April

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Madam
Mirs Jane Allison DOR g7. 024
ting in response to your Regulation 28 Report

ler discussion with practice partners and colleagues we have come up with the following
lan

An email has been sent to all prescribing clinicians alerting them to the rare but significant
and potential life threatening side effects of nitrofurantoin causing acute breathlessness and
the need to advise patients to promptly report such symptoms,

We will discuss this further in our next Significant Event Analysis Meeting

We are also looking into our information technalogy to help us give written information to
te patients about the side effects of this medication

One of our partners has agreed to write to the Local Medicine Management Team

highlighting this life threatening side effect and expecting possible changes to the local
guidelines

'f you do need any further information please don’t hesitate to contact us.

Many th

anks

Yours sincerely

Dr
Response from Mhra (PDF)
Mr. Crispin Oliver 
Assistant Coroner for County Durham and Darlington  
H.M. Coroners Office  
P.O. Box 282 
Bishop Auckland 
Co. Durham 
DL14 4FY 

MHRA 
10 South Colonnade 
Canary Wharf 
London 
E14 4PU 

www.gov.uk/mhra 

18 July 2022 

Dear Mr Oliver, 

Regulation 28 Report concerning Jane Elizabeth Allison (nitrofurantoin) 

Thank you for your email dated 14th April 2022, in which you asked the Medicines and Healthcare 
products Regulatory Agency (MHRA) to provide a response to the Regulation 28 Report to Prevent 
Future Deaths following the inquest into the sad death of Ms Jane Elizabeth Allison.  

Your report identified a number of matters of concern, including the following points relating to 
information available for healthcare professionals about the potential pulmonary side effects of 
nitrofurantoin: 

1.  The patient died of acute pulmonary damage following the administration of 

nitrofurantoin for a urinary tract infection (course of treatment 10 days), however the BNF 
does not advise healthcare professionals to be alert to the danger of sudden pulmonary 
deterioration in elderly patients.   

2.  The BNF is deficient in providing advice as to monitoring and being alert for acute 

pulmonary damage. If the patient or her GP had been aware of this possible side effect, 
they might have been able to intervene earlier to avoid her death. 

3.  The information sent out with nitrofurantoin should be reviewed. 

The MHRA is the 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). 

As you have noted, the product information for nitrofurantoin does list pulmonary and respiratory 
issues as possible side effects. We have conducted a review of the available evidence concerning 
nitrofurantoin and pulmonary adverse drug reactions and sought expert advice from the 
Pharmacovigilance Expert Advisory Group (PEAG) of the Commission on Human Medicines on the 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 strength of the evidence and whether the nitrofurantoin product information should be further 
amended. 

As you will be aware, nitrofurantoin has been widely used in the UK since the 1950s for the 
treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections 
or pyelitis either spontaneous or following surgical procedures. Aside from Ms Allison’s case, as of 
10th May 2022, we have received a small number of other fatal Yellow Card reports of nitrofurantoin 
and respiratory failure, with other durations of use. Some of these cases offer possible alternative 
explanations for the events, either due to the patient’s previous medical history or concomitant 
medications that are themselves associated with respiratory reactions.   

The PEAG agreed that pulmonary adverse reactions in patients taking nitrofurantoin are generally 
well known and that the frequency of these events appears low. Furthermore, there are no 
significant new data on the risk considering the cumulative exposure to this drug in the UK which is 
likely to be in the order of millions of people. It was agreed that awareness amongst healthcare 
professionals and patients should be improved so they are alert for any new breathing symptoms 
when taking nitrofurantoin.  

Action being taken by the MHRA 

In summary, we have considered the available evidence on nitrofurantoin and acute pulmonary 
reactions and, based on expert advice from the PEAG, will request that Marketing Authorisation 
Holders (MAHs) strengthen the wording in the UK Summary of Product Information (SmPC) and 
Patient Information Leaflet (PIL).  

We are aware that the BNF, which is not the responsibility of the MHRA, has recently updated the 
nitrofurantoin monograph. These updates, adding additional information on acute pulmonary 
reactions, are in line with the current UK SmPC and PIL. The MHRA will communicate any SmPC 
and PIL updates, to the BNF, so that they can further revise their monograph as needed.  

Companies marketing nitrofurantoin will be requested to emphasise to healthcare professionals and 
patients/carers in the nitrofurantoin product information the need to be vigilant for respiratory 
symptoms including during use to treat acute urinary tract infections, and to ensure that these 
warnings are sufficiently prominent.  

The PEAG also agreed that it would be appropriate to communicate to UK healthcare professionals 
to inform them of these updates and remind them of the potential for pulmonary and chronic 
adverse drug reactions in association with nitrofurantoin, and that any such symptoms should be 
investigated and reported promptly. The PEAG considered that an article in the MHRA’s monthly 
‘Drug Safety Update’ bulletin may be an appropriate method to communicate these messages, and 
we will be taking this forward. 

We will continue to keep the issue of nitrofurantoin and acute pulmonary reactions under close 
review, and we will let you know when the product information updates are complete and the Drug 
Safety Update Bulletin has been issued. 

 
 
 
 
 
 
 
 
 
 Yours sincerely 

Chief Executive 
Medicines and Healthcare products Regulatory Agency
Response from Nice (PDF)
2nd Floor 
2 Redmond Place 
London 
E20 1JQ 
United Kingdom 

22 March 2022 

Mr Crispin Oliver 
Assistant Coroner for County Durham and Darlington 
H.M. Coroners Office 
P.O. Box 282 
Bishop Auckland 
Co. Durham 
DL14 4FY 

Dear Mr Oliver, 

I write in response to your correspondence, sent to NICE on 7 March 2022, regarding the 
very sad death of Jane Allison. I would like to offer my sincere condolences to Jane’s family. 

We have reflected on the circumstances surrounding Ms Allison’s death, and the concerns 
raised in your report regarding the British National Formulary (BNF) entry for nitrofurantoin. 

The BNF is a joint publication of BMJ Group and Pharmaceutical Press, the publishing 
division of the Royal Pharmaceutical Society. While we make the BNF available on the NICE 
website, responsibility for the content remains with the publishers and therefore NICE cannot 
comment on the concerns you have raised.  

I am aware that your report has also been sent to the chief executive of the Royal 
Pharmaceutical Society who will be better placed to respond to your concerns. 

You may also wish to contact the Medicines and Healthcare products Regulator Authority 
(MHRA) with respect to the summary of product characteristics for nitrofurantoin. 

Yours sincerely, 

Dr 
Chief executive
Response from Royal Pharmaceutical Society (PDF)
BNF Publications 
bnf.org 
________________________________________________________________________________ 

Mr Crispin Oliver 
H.M. Coroners Office 
PO Box 282 
Bishop Auckland 
Co Durham 
DL14 4FY 

23rd March 2022 

Dear Mr Oliver, 

We write in response to your Regulation 28 report dated 7th March 2021 which was forwarded to us 
as the Publisher of the British National Formulary. We are sorry to hear the sad circumstances 
surrounding this case. 

We have reviewed the BNF content for nitrofurantoin in response to your report and can confirm that 
we will add additional information regarding acute pulmonary reactions to the nitrofurantoin 
monograph in the BNF. To increase awareness of this side-effect, we will highlight it specifically in an 
additional section of the side-effects information. We will also add information on the importance of 
counselling patients on the possible symptoms of acute pulmonary reactions and the necessity of 
promptly reporting such symptoms. This will mean that the risk of acute pulmonary reactions will be 
highlighted in the nitrofurantoin monograph in future. 

We trust that this addresses this important issue. 

Yours sincerely, 

Associate Content Director (BNF Publications) 

________________________________________________________________________________ 

Royal Pharmaceutical Society  
66-68 East Smithfield, London E1W 1AW

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