Prevention of Future Deaths reports · 2016

Raymond Woodward

Regulation 28 report to prevent future deaths, reference 2016 – 0308, written 26 Aug 2016. A coroner writes one of these when an inquest reveals a risk that could cause further deaths unless something changes.

Date of report26 Aug 2016
Reference2016 – 0308
DeceasedRaymond Woodward
CoronerEmma Brown
Coroner areaBirmingham and Solihull
CategoryAlcohol, drug and medication related deaths
Sourcejudiciary.uk record · original PDF
Responses published2

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

THIS REPORT IS BEING SENT TO:
1, Medicines & Healthcare products Regulatory Agency.

CORONER

lam Emma Brown Area Coroner for Birmingham and Solihull

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.

INVESTIGATION and INQUEST

On 31/05/2016 | commenced an investigation into the death of Raymond Charles Woodward. The
investigation concluded at the end of the inquest on the 18th August 2016. The conclusion of the inquest
was:

“Death during a routine medical investigation as a result of a reaction to medication given in conjunction
with previously undiagnosed coronary artery disease.”

CIRCUMSTANCES OF THE DEATH

The Deceased passed away in the accident and emergency department of the Queen Elizabeth Hospital,
Birmingham on the 19th February 2016 having suffered a cardiac arrest whilst undergoing a colonoscopy
for the investigation of abdominal pain, dyspepsia and constipation at the Edgbaston BMI Hospital. The
colonoscopy had been proceeding normally when the Deceased suddenly deteriorated after the
administration of Buscopan to reduce spasm. Despite comprehensive cardio-pulmonary resuscitation he
did not regain circulation. He was transferred to the Queen Elizabeth Hospital to maximise treatment if
resuscitation were achieved but was declared deceased at 18.10.

Following a post mortem examination and toxicological analysis the Cause of Death was determined as:
1(a) CARDIORESPIRATORY ARREST
1(b) CORONARY ARTERY DISEASE AND A REACTION TO ADMINISTERED BUSCOPAN

Evidence was provided to me there have been 5 reported instances of adverse reactions to Buscopan in
the presence of coronary artery disease resulting in death. it is reasonable to suppose that there could be
more unreported instances.

CORONER’S CONCERNS

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

The MATTERS OF CONCERN are as follows. —

(1) The risk of an adverse reaction to Buscopan in the presence of coronary artery disease is not
widely known despite the wide use of Buscopan.

{2} The SPC relating to the use of intravenous Buscopan references the following in relation to the
cardiovascular system — ‘Buscopan Ampoules should be used with caution in conditions
characterised by tachycardia such as thyrotoxicosis, cardiac insufficiency or failure and in cacdiac__

surgery where it may further accelerate the heart rate’.

(3) The term ‘cardiac insufficiency’ is unwieldy and does not immediately relate to a specific
diagnosis, lacks specificity and does not necessarily encompass those patients with ischaemic
heart disease.

(4) ERR the Deceased’s Consultant Physician and Gastroenterologist, gave firm
evidence, having extensively researched the issue, that the wider medical community needs to
be alerted to potential cardiovascular problems in using lV Buscopan and this could be achieved
by incorporating into the SPC ‘additional caution should be exercised in administering IV
Buscopan to patients with ischaemic heart disease’.

ACTION SHOULD BE TAKEN

{n my opinion action should be taken to prevent future deaths and | believe you have the power to take
such action.

This opinion was fully supported by EB anc also aaa Consultant Cardiac Anaesthetist
who lead Mr. Woodward’s resuscitation.

YOUR RESPONSE

You are under a duty to respond to this report within 56 days of the date of this report, namely by 14”
October 2016. 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.

COPIES and PUBLICATION

| have sent a copy of my report to the Chief Coroner and to the following Interested Persons: Mr.
Woodward’s family, the BMI Edgbaston Priory and

1am 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.

26/08/2016

Signature
Emma Brown Area Coroner Birmingham and Solihull

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 Medicines and Healthcare Products Regulatory Agency (PDF)
Medicines and Healthcare
| Products Regulatory Agency
eee

151 Buckingham Palace Road
Victoria

London SW1W 9SZ

United Kingdom

Emma Brown

Area Coroner
Birmingham and Solihull
50 Newton Street
Birmingham B4 6NE

7 December 2016
Dear Ms Brown
RE: RAYMOND CHARLES WOODWARD, DECEASED, date of death 19/02/16 (Ref: 113062)

Thank you for your report dated 26" August 2016 regarding the investigation and inquest into the death of
Raymond Charles Woodward (Regulation 28 Report to Prevent Future Deaths).

The MHRA as a regulatory agency has a responsibility to ensure that medicines are efficacious and
acceptably safe and that guidance on the use of a medicine, including warnings and precautions for
prescribers and patients, is appropriately described in the authorised product information, the Summary of
Product Characteristics (SmPC) and Patient Information Leaflet.

A post-mortem of Mr Woodward showed that he died from cardiorespiratory arrest due to coronary artery disease
and a reaction to intravenous Buscopan Ampoules, which had been administered as part of a barium enema
investigation. Buscopan Ampoules, administered intramuscularly or intravenously, are licensed to reduce bowel
spasm in diagnostic procedures, such as barium enema. Your report highlights a concern that the risk of life-
threatening adverse reactions to Buscopan Ampoules in patients with coronary heart disease is not adequately
addressed in the SmPC. Specifically, you refer to the following warning in section 4.4 of the SmPC for Buscopan
Ampoules:

“Buscopan Ampoules should be used with caution in conditions characterised by tachycardia such as
thyrotoxicosis, cardiac insufficiency or failure and in cardiac surgery where it may further accelerate the heart
rate.”

You note that the term “cardiac insufficiency” does not relate to a specific diagnosis and does not necessarily
encompass patients with coronary heart disease. In your report you state that the Deceased’s Consultant
Physician a has suggested that this point can be addressed by including the following statement
in section 4.4 of the SmPC for Buscopan Ampoules:

“Additional caution should be exercised in administering IV Buscopan to patients with ischaemic heart disease.”

To determine what regulatory action, if any, is required with respect to Buscopan Ampoules we have analysed all
the reported deaths in the UK that were suspected as being caused by Buscopan Ampoules and reviewed the
current product information.

From our safety database we have identified eight reported fatal cases in the UK (including the death of Mr
Woodward) where a causal relationship between Buscopan Ampoules and a fatal outcome is likely. In two of
these eight fatal cases, there were pre-existing cardiac conditions. In three of the remaining six fatal cases
medical history was not reported and in the other three cases there was no mention of cardiac disease in the
medical history, although the cases were not well described.

#8 CPRD £4 NIBSC

Te eo?

Section 4.8 of the SmPC of Buscopan Ampoules lists several side effects which could be more serious in patients
with coronary heart disease. These include tachycardia, blood pressure reduced and serious allergic reactions
(anaphylaxis), which can cause a severe drop in blood (shock) and in more serious cases can result in cardio-
respiratory arrest. Several publications have noted that anaphylaxis is more likely to be fatal in patients with
underlying coronary heart disease.'?

Given that the risk of serious cardiac side effects due to Buscopan Ampoules is more likely in patients with
cardiac conditions, such as coronary heart disease, we agree that the product information should be updated to
more clearly communicate and minimise this risk in these patients. We have therefore written to the Company
who hold the licence for Buscopan Ampoules and requested that they update the product information accordingly.
The Company has agreed to revise the warning in section 4.4 of the SmPC which you highlighted as not
adequately describing the risk in patients with coronary heart disease. The warning will recommend caution when
using Buscopan Ampoules in patients with cardiac disease, including coronary heart disease, because of the risk
of tachycardia, hypotension and anaphylaxis. In addition, the revised warning will recommend monitoring of these
patients and that emergency equipment and personnel trained in its use must be readily available. The wording
will be finalised once the Company submits an application to vary the product information, but is expected to be in
line with the following:

"Buscopan Ampoules can cause tachycardia, hypotension and anaphylaxis, therefore use with caution in patients
with cardiac conditions, such as cardiac failure, coronary heart disease, cardiac arrhythmia or hypertension, and
in cardiac surgery. Monitoring of these patients is advised. Emergency equipment and personnel trained in its use
must be readily available."

At the time that the product information is updated we also propose to communicate these new recommendations
through an article in our MHRA newsletter, Drug Safety Update, which will be circulated to relevant healthcare
professionals.

| will write to you again once the product information has been updated and the DSU article is published.
Thank you for drawing our attention to this important issue.

Yours sincerely
es,
Ag
AN

Dr lan Hudson,

Chief Executive Officer

Medicines and Healthcare products Regulatory Agency
151 Buckingham Palace Road, London, SW1W 9SZ

1. Mueller UR. Cardiovascular disease and anaphylaxis. Curr Opin Allergy Clin Immunol
2007;7:337-41.

2. Triggiani M, Patella V, Staiano RI, et al. Allergy and the cardiovascular system. Clin Exp
Immunol 2008;153:7-11.
Response from Medicines and Healthcare Products Regulatory Agency2 (PDF)
Emma Brown 
Area Coroner 
Birmingham and Solihull 
50 Newton Street 
Birmingham B4 6NE 

1 March 2017 

Dear Miss Brown 

151 Buckingham Palace Road 
Victoria 
London SW1W 9SZ 
United Kingdom 

RE: RAYMOND CHARLES WOODWARD, DECEASED, date of death 19/02/16 (Ref: 113062) 

Further to my letter dated 7 December 2016 regarding the inquest into the death of Raymond Charles 
Woodward, I can confirm that the Summary of Product Characteristics (SmPC) for Buscopan Ampoules 
has been updated to more clearly communicate and minimise this risk of serious adverse reactions in 
patients with underlying cardiac disease. Section 4.4 of the SmPC has been revised with the following 
warning:  

Buscopan Ampoules can cause tachycardia, hypotension and anaphylaxis, therefore use with caution 
in patients with cardiac conditions such as cardiac failure, coronary heart disease, cardiac arrhythmia or 
hypertension, and in cardiac surgery. Monitoring of these patients is advised. Emergency equipment 
and personnel trained in its use must be readily available. 

We have also communicated these new recommendations to healthcare professionals through an 
article in our MHRA newsletter, Drug Safety Update, which is available at https://www.gov.uk/drug-
safety-update  

Yours sincerely 

Dr Ian Hudson, 
Chief Executive Officer 
Medicines and Healthcare products Regulatory Agency 
151 Buckingham Palace Road, London, SW1W 9SZ 
www.mhra.gov.uk

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