Linda McLaughlin

10 South Colonnade 
Canary Wharf 
London 
E14 4PU 
United Kingdom 
gov.uk/mhra 

Ms Alison Mutch  
Senior Coroner for South Manchester 
By Email: 

Reference: 

23 January 2025 

Dear Ms Mutch, 

Regulation 28 Report into the death of Linda McLaughlin 

Thank you for your Regulation 28 Report relating to the death of Linda McLaughlin on 27 
October 2023 which was received on 31 October 2024. I would like to offer my sincere 
condolences to Mrs McLaughlin’s family on their tragic loss. I apologise for a delay in 
responding to you, contact was made with your office by telephone, to explain the situation 
on 5 November 2024. 

As described in your report Mrs McLaughlin was diagnosed with Chronic Myeloid Leukaemia 
(CML) in 2014 and was treated with nilotinib. Following response to treatment she was in 
molecular remission by October 2021. Nilotinib treatment continued at a low dose. Mrs 
McLaughlin subsequently went on to be diagnosed with interstitial lung disease in May 2023 
which was treated with steroids and her nilotinib was stopped. In October 2023 Mrs 
McLaughlin developed bronchopneumonia and sadly died as a result. 

I note the Regulation 28 report was initially sent to NHS England and in their response dated 
5 August 2024, NHS England suggested your concerns should also be sent to the MHRA. 

 Your report identified the following matters of concern relating to nilotinib (Tasigna): 

1.  The inquest heard evidence that the complication Mrs McLaughlin developed is rare 

but recognised internationally. However, it is not widely known about and as a 
consequence of lack of awareness even amongst oncologists/haematologists it may 
not be recognised that a patient has symptoms of interstitial lung disease and as a 
consequence referral and treatment that could slow the disease progression may be 
delayed. 

 
 
 
 
 
 
 
 
 
 
 
 
 2.  The inquest was told that the consenting process for starting a patient on a drug such 

as nilotinib would not ordinarily include mentioning rare complications such as 
interstitial lung disease. The family gave evidence that in this case this is something 
that would have been carefully weighed in the decision to proceed with the treatment. 

3.  ln this case the inquest was told that a decision was taken to continue with nilotinib 
despite being in remission. The inquest was told that there is growing evidence that 
some people do not need to stay on these drugs for life if in remission but there is no 
clear guidance for the approach to take. As a consequence, patients may remain on 
the drug longer than necessary. 

I will address each of these concerns in turn but first provide some background on the 
MHRA.   

The MHRA regulates medicines, medical devices, and blood components for transfusion in 
the United Kingdom to ensure that they meet robust standards of safety, quality and efficacy. 
Unfortunately, no medicine is completely without risk. All medicines have the potential to 
cause side effects, and these are outlined in the product information for each medicine. The 
product information comprises of:  

•  Summary of Product Characteristics: (SmPC) a document describing the properties 
and the officially approved conditions of use of a medicine. SmPC forms the basis of 
information for healthcare professionals on how to use the medicine safely and 
effectively  

•  Patient Information Leaflet (PIL): The leaflet in every pack of medicine that contains 

information for patients on the medicine and its use. 

The benefits and risks of all medicines, including nilotinib, are continually and rigorously 
assessed throughout the lifecycle of the product using a range of different sources of 
information. When necessary, the MHRA will take action to ensure the benefits of a product 
continue to outweigh the risk. This may include changing the product information to include 
warnings of additional side effects or other changes in how the medicine is used.  

When assessing whether a drug may have caused a suspected side effect, it is also 
important to consider a number of other factors such as the full diagnosis, past medical 
history, previous treatments and concomitant medications.    

I will address concerns that there was a lack of awareness of the side effect of interstitial 
lung disease among healthcare professionals and the provision of information to patients. 

Nilotinib has been licenced for marketing in the UK since November 2007. The SmPC and 
the PIL include the known side effects of this cancer medicine. Interstitial lung disease is an 
uncommon side effect of nilotinib and currently there is information provided in the SmPC 
and the PIL.  

2 

 
 
 
 
 
 
 
 
 
 
 
 
 
 The text is provided below: 

•  The SmPC for Tasigna (nilotinib) 
Section 4.8 of the SmPC lists Adverse reactions from clinical studies and post-marketing 
reports (Table 3) - pneumonia is listed as a common side effect (estimated to affect 
between 1 in 100 and 1 in 10 patients). Interstitial lung disease is listed as an uncommon 
side effect (estimated to affect between 1 in 1000 and 1 in 100 patients) 

•  The PIL for nilotinib –  
The PIL includes the following general information:  
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.  
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist… 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible 
side effects not listed in this leaflet…. 

The PIL explains that like all medicines, nilotinib can cause side effects, although not 
everybody gets them. Section 4 of the PIL includes information about “Possible side 
effects”. It also provides information about signs of lung disorders in general and 
interstitial lung disease as follows:  

Some side effects could be serious. 
…………………… 
signs of lung disorders: difficulty breathing or painful breathing, cough, wheezing with 
or without fever, swelling of the feet or legs 
……………………….. 
Some side effects are common (may affect up to 1 in 10 people)  
- pneumonia 
……………………… 
Some side effects are uncommon (may affect up to 1 in 100 people) 
……………………….. 
signs of interstitial lung disease: cough, difficulty breathing, painful breathing... 

The second concern raised relates to continuation of nilotinib therapy following remission.  

The SmPC for Tasigna (nilotinib) includes detailed information about discontinuation of 
treatment with nilotinib in case of sustained deep molecular response in eligible patients, 
monitoring and measurement of molecular response, loss of remission and nilotinib 
reinitiation where appropriate. Health Care Professionals are also reminded in the SmPC 
that Treatment should be continued as long as clinical benefit is observed or until 
unacceptable toxicity occurs….” 

The MHRA recognises that as the medicines’ regulator, it is not within our remit to comment 
on clinical practice issues. It is a healthcare professional’s responsibility to prescribe a drug 
based on the information contained within the SmPC and to obtain appropriate consent after 
counselling the patient on their individual benefits and risks with use. 

3 

 
 
 
 
 
  
 
 Overall, the MHRA considers that the information provided in the SmPC and PIL for nilotinib 
adequately reflects the current scientific evidence available and no updates are required. 
However, we note the concern raised about a lack of awareness of the side effect of 
interstitial lung disease.  

The British National Formulary (BNF) is a valuable source of information for healthcare 
professionals and we have noted that the BNF drug monograph for nilotinib includes the 
term “respiratory disorders” as a side-effect, which covers a range of respiratory side-effects, 
including interstitial lung disease. The publishers of the BNF are a separate organisation to 
the MHRA. We have reached out to the BNF editorial team and have asked them to consider 
including interstitial lung disease as a separate side-effect term in the nilotinib drug 
monograph.  

The BNF have informed us ‘interstitial lung disease’ will appear as a separate term in the 
side-effects sections of relevant BNF and BNF for Children (BNFC) monographs in the 
January 2025 online updates of BNF and BNFC and the BNF + BNFC app. This update will 
be included in the next print edition of BNF which will be published in March 2025. 

The MHRA collects and monitors information about adverse effects of medicines through the 
Yellow Card Scheme. Patients, carers, parents and healthcare professionals in the UK are 
encouraged to report suspected side effects through the Yellow Card scheme using 
https://yellowcard.mhra.gov.uk/ website, the app or through some healthcare professional IT 
clinical systems. There is also guidance on what to report. I am grateful to you for bringing 
this report to our attention and I can confirm that the side effects experienced by Mrs 
Mclaughlin have now been included in the MHRA Yellow Card database (reference number 
is 34193346). 

As with all medicines including nilotinib, the MHRA will continue to monitor the safety of them 
and where necessary, take action to ensure that a medicine continues to be used in a way 
which minimises risk and maximises benefits to the patient.  

Once again, we thank you for bringing these important patient safety issues to our attention 
and should you have any further questions, please do not hesitate to contact me.  

Yours sincerely, 

Chief Executive 
Medicines and Healthcare products Regulatory Agency 
E: 

4

Ms Alison Mutch  
HM Senior Coroner  
Manchester South Coroner’s Court 
1 Mount Tabor Street 
Stockport 
SK1 3AG 

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

05/08/2024 

Dear Coroner, 

Re: Regulation 28 Report to Prevent Future Deaths – Linda McLaughlin who 
died on 27 October 2023  

Thank  you  for  your  Report  to  Prevent  Future  Deaths  (hereafter  “Report”)  dated  13 
June 2024 concerning the death of Linda McLaughlin on 27 October 2023. In advance 
of responding to the specific concerns raised in your Report, I would like to express 
my  deep  condolences  to  Linda’s  family  and  loved  ones.  NHS  England  are  keen  to 
assure the family and the Coroner that the concerns raised about Linda’s care have 
been listened to and reflected upon.   

Your Report raises the concern that it is not widely known by healthcare professionals 
that  interstitial  lung  disease  is a  rare  side effect  of  treatment  with  a  tyrosine  kinase 
inhibitor drug called nilotinib, and that the consenting process for such a drug would 
not usually include mentioning such rare complications.  

Your concerns and the circumstances of Linda’s care have been shared with specialist 
Patient Safety and Cancer colleagues at NHS England. It is noted that interstitial lung 
disease  is  listed  in  the  Summary  of  product  characteristics  for  nilotinib  as  an 
uncommon respiratory side effect (see section 4.8) and the British National Formulary 
(BNF), which provides key information on the selection, prescribing, dispensing and 
administration  of  medicines  for  healthcare  professionals,  also  lists  respiratory 
disorders as an uncommon side effect of the drug. The Patient Information Leaflet also 
makes  mention  of  lung  disorders  as  possible  (uncommon)  side  effects,  including 
“signs of interstitial lung disease: cough, difficulty breathing, painful breathing”, so this 
information should have been available to the prescribers and the patient.   

It is, however, acknowledged that the list of potential side effects is quite long, and it 
is unlikely that an uncommon complication such as this would normally be discussed 
when obtaining a patient’s consent. It is a matter of individual clinical judgement about 
how extensive a discussion of potential but uncommon side effects should be. It would 
be expected that any patient developing respiratory symptoms while taking nilotinib 
would normally undergo rapid investigation and sometimes temporary cessation of the 
nilotinib treatment. 

It should be noted that NHS England does not administer the BNF, and that regulation 
of medication does not sit within our remit. You may wish to revert to the BNF and/or 

                                                                                                                       
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 the Medicines & Healthcare products Regulatory Agency (MHRA), as the regulator of 
medicines used in the UK, who would be more appropriate to respond to your concerns 
on this matter.  

Your Report also raises that there is growing evidence that some people do not need 
to stay on tyrosine kinase inhibitor drugs for life once in remission, but that there is no 
clear guidance on this and that consequently patients may remain on the drug longer 
than necessary. Again, you may wish to direct this concern to the MHRA who would 
be more appropriate to comment. However, specialist cancer colleagues have advised 
that this is an issue that currently remains in evolution. A proportion of patients can 
stop  taking the drugs once  they achieve  a durable molecular remission,  and  this is 
normally discussed with patients after a certain length of time, weighing the potential 
toxicity  of  ongoing  treatment  against  the  risk  of  recurrence.  The  British  Society  for 
Haematology has an extensive guideline addressing this issue.   

I  would  also  like  to  provide  further  assurances  on  the  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 events, such as the sad death of Linda, 
are shared across the NHS at both a national and regional level, and helps us to 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