Prevention of Future Deaths reports · 2014

Akua Anokye-Boateng

Regulation 28 report to prevent future deaths, reference 2014-0211, written 9 May 2014. A coroner writes one of these when an inquest reveals a risk that could cause further deaths unless something changes.

Date of report9 May 2014
Reference2014-0211
DeceasedAkua Anokye-Boateng
CoronerAndrew Harris
Coroner areaLondon Inner (South)
CategoryAlcohol, drug and medication related deaths
Sourcejudiciary.uk record · original PDF
Responses published1

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) Dr lan Hudson, Chief Executive Medicines and Healthcare Products Regulatory
Agency (MHRA), 151 Buckingham Palace Road, London SW1W 9SZ

: CORONER

| am Dr Andrew Harris, Senior Coroner, London Inner South

| CORONER’S LEGAL POWERS

| 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.

INQUEST

On 23rd January 2013, | opened an inquest into the death of:
Miss Akua Anokye-Boateng, aged 7 years, died 16th January 2013,
Case Ref: 00154-13.

It was concluded on 26th March 2014.

The court found that the medical cause of death was:

1a Acute Peritonitis and Shock

1b Perforated Duodenum

1¢ Non steroidal anti-inflammatory (NSAID) ingestion and Helicobacter associated
chronic ulceration of duodenum in sickle cell disease

CIRCUMSTANCES OF THE DEATH

The following narrative was recorded:

Akua had weil managed and well controlled sickle cell disease. She suffered a 3 day
ifiness, consulting her GP but collapsing suddenly, unresponsive to prompt resuscitation
and dying at 19.16 at KCH on 16.01.13. She had ingested a non steroidal anti-
inflammatory drug in May 2012 and suffered a GI upset in August. Her death was
unrelated to sickle disease and was caused by unexpected duodenal perforation,
although chronic and multi-factorial.

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 will occur unless action is taken. in the
circumstances it is my statutory duty to report to you.

The MATTER OF CONCERN is as follows. —

Expert evidence was heard from an experienced academic pathologist that one dose of
NSAID was sufficient to damage the G! mucosa in children, which, coupled with a
presumed Helicobacter infection, led in this case to the perforation. The consultant
paediatrician with responsibility for haemoglobinopathies was unaware of the risk of a
single dose in the past and gave evidence that Ibuprofen was an important drug in the
management of sickle cell patients, having less side effects than opiates. He reported
that it is not current practice to routinely give gastro-intestinal protection when NSAIDs
are used briefly in children with sickle disease. Thus it is unclear what is best practice or
whether the scientific evidence suggests that guidance is needed for clinicians about
further precautions or prevention such as Proton pump inhibitors being routinely used
alongside NSAIDs in children, to minimize the risk of similar deaths.

6 | ACTION SHOULD BE TAKEN

In my opinion action should be taken to prevent future deaths and | believe that the
general practitioner and medical director 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 Friday 4h July 2014. |, 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.

If you require any further informati i the case, please contact the

8 | COPIES and PUBLICATION

| have sent a copy of my report to the Chief Coroner and to the followi cd
Persons: a: °( nt it il
consultant haematologist and le ant pathologist, who
may find it useful or of interest.

| 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.

[SIGNED BY COR@GNE

Responses

1 response 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 Medicine Healthcare Products Regulatory Agency (PDF)
Medicines and Healthcare
Products Regulatory Agency
Se0

Dr Andrew Harris 151 Buckingham Paiace Road
Senior Coroner for Inner London South District London SW1W 9SZ

Inner London South Coroner’s Court United Kingdom

1 Tennis Street

Southwark mhra.gov.uk

London

SE11YD

Your ref: 154/2013
18 July 2014
Re: Miss Akua Anokye-Boateng (Regulation 28 Report to Prevent Future Deaths)

Dear Dr Harris

Thank you for your letter dated 9" May 2014 and bringing to my attention the circumstances of the
death of Miss Akua Anokye-Boateng (Regulation 28 Report to Prevent Future Deaths).

On reading your Prevent Future Deaths (PFD) report | identified two distinct points for MHRA to
address. These are:

a) the apparent lack of awareness amongst healthcare professionals that there is the potential for
serious gastrointestinal toxicity to occur with short-term use of NSAIDs; and

b) whether gastrointestinal protective agents should be routinely used alongside NSAIDs in
children.

The MHRA has sought the advice of its Pharmacovigilance Expert Advisory Group of the Commission
on Human Medicines regarding any necessary actions to address these concerns.

| set out below the actions.

a) Healthcare professional awareness of the potential for serious gastrointestinal toxicity to
occur with short-term use of NSAIDs.

Following a number of national and Europe-wide reviews of the gastrointestinal safety of NSAIDs, a set
of key elements was agreed for inclusion in the Summary of Product Characteristics (SPC) for all non-
selective NSAIDs available as prescription only medicines (POM). These key elements include
contraindications to use and extensive warnings in relation to the gastrointestinal side effects.

MHRA also formulated a set of key elements for inclusion in the SPC for ibuprofen-containing products
available in the UK without prescription as Pharmacy (P) or General Sales List (GSL) medicines.

| attach a copy of the key elements for POM non-selective NSAIDs and also for P and GSL ibuprofen.

These were implemented for all relevant products (including products authorised for use in children) in
the UK in 2008. ;

2 CPRD 4: NIBSC

Medicines and Healthcare .
Products Regulatory Agency
eee

The SPCs for POM, P and GSL NSAIDs including ibuprofen state the following in section 4.4 (Special
warnings and precautions for use):

‘GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any
time during treatment, with or without warning symptoms or a previous history of serious GI events.’

The MHRA and its independent experts consider that this statement in the SPC is sufficient to alert
readers to the possibility of serious gastrointestinal side effects occurring early in NSAID treatment.
However, we acknowledge that healthcare professionals do not always read the SPC before
prescribing, particularly when prescribing commonly used medicines, and your report highlights that
there are some healthcare professionals who are unaware of this fact. Therefore we propose to inform
and remind healthcare professionals about this through an article in the September 2014 issue of our
monthly bulletin ‘Drug Safety Update’.

b) Should gastroprotective agents be routinely given alongside NSAIDs in children?

The SPCs for all POM non-selective NSAIDs include a recommendation to use gastro-protective
agents (proton pump inhibitors or misoprostol) when prescribing NSAIDs to those at high risk of
gastrointestinal side-effects, as follows:

‘The risk of G! bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with
a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in
the elderly. These patients should commence treatment on the lowest dose available. Combination
therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for
these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to
increase gastrointestinal risk (see below and 4.5).’ .
This recommendation is also included in the SPCs for POM non-selective NSAIDs authorised for use in
children.

For non-prescription use of ibuprofen in adults and children, a recommendation for the concurrent use
of PPIs is not included in the SPC. For those NSAIDs available over-the-counter, the authorised doses
are lower than prescription-only products, and the indications only cover short term self-limiting
conditions which do not require diagnosis & supervision by a medical practitioner. Patients (or parents
of patients) at high risk of gastrointestinal side effects who purchase ibuprofen as an over-the-counter
product are advised in the package leaflet to discuss taking these products with their doctor so that
they can be properly advised about the need for gastro-protective medicines to be taken at the same
time.

After careful consideration of the details of the case presented in your PFD report, the MHRA and its
independent experts do not consider that this case changes the overall benefit-risk balance of ibuprofen
in children or warrants a change to the current warnings about the need for gastro-protective agents for
prescription only medicines. However, for all NSAIDs we will be strengthening the information for
patients/parents provided in the package leaflet on the risk and recognition of gastrointestinal side
effects and the action they should take.

In summary, in response to your report under Regulation 28 to Prevent Future Deaths, concerning the

death of Miss Akua Anokye-Boateng, MHRA will take the following action to help minimise risk from the
gastrointestinal side-effects of NSAIDs:

#8 CPRD ig NIBSC

edicines and Healthcare

Products Regulatory Agency

Proposed action

Purpose of proposed action

Timeline for action

Drug Safety Update (DSU)
article

(www. mhra.gov.uk/drugsafet
yupdate)

To remind healthcare professionals of information

already included in the SPCs for NSAIDs, that:

« the GI side-effects of NSAIDs can be serious and
life-threatening. Fatalities have been reported.

e serious Gl side-effects can occur with short-term
use of NSAIDs

e serious Gl side-effects can occur in people who

may be considered to be at low risk, including in
children

Publication in the
September 2014 issue
of DSU

Strengthen the Patient
Information for all NSAIDs
with regards to GI risk.

e To strengthen the NSAID product information
provided to patients/parents on the risk.

e To aid patient/parent recognition of gastrointestinal
side-effects and provide information on the action
they should take if symptoms arise

Review and implement
changes within 12
months.

| hope that this response addresses your concerns

Yours sincerely

Dr lan Hudson
Chief Executive, MHRA

Telephone: +44 wee 3080 6100
Email:

#8 CPRD

“## NIBSC

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