Chloe Burgess
PFD Report
All Responded
Ref: 2025-0121
All 2 responses received
· Deadline: 28 Apr 2025
Response Status
Responses
2 of 2
56-Day Deadline
28 Apr 2025
All responses received
About PFD responses
Organisations named in PFD reports must respond within 56 days explaining what actions they are taking.
Source: Courts and Tribunals Judiciary
Coroner’s Concerns
During 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. The inquest heard evidence that the potential dangers of the combination of amitriptyline, paroxetine and ivabradine is not widely appreciated and does not trigger an alert on the prescribing software used in primary care or by pharmacists. The potential dangers related to a failure to metabolise amitriptyline which can, incrementally, lead to toxicity. I am also concerned that those prescribing ivabradine should have a full understanding of the potential interaction with amitriptyline and paroxetine.
Responses
NICE acknowledges the concerns regarding drug interactions but states they cannot address them as responsibility for the content of the British National Formulary (BNF), where the relevant information would be held, lies with its publishers, not NICE.
AI summary
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Dear Mr Walker,
I write in response to your regulation 28 report, sent to NICE on 4 March 2025, regarding the very sad death of Chloe Elizabeth Burgess. I would like to offer my sincere condolences to Chloe’s family.
We have reflected on the circumstances surrounding Chloe’s death, and the concerns raised in your report regarding drug interactions. The British National Formulary (BNF) provides key information on the selection, prescribing, dispensing and administration of medicines and we believe that they would be best placed to address your concerns.
The BNF is a joint publication of the 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.
Your sincerely, Chief Executive
I write in response to your regulation 28 report, sent to NICE on 4 March 2025, regarding the very sad death of Chloe Elizabeth Burgess. I would like to offer my sincere condolences to Chloe’s family.
We have reflected on the circumstances surrounding Chloe’s death, and the concerns raised in your report regarding drug interactions. The British National Formulary (BNF) provides key information on the selection, prescribing, dispensing and administration of medicines and we believe that they would be best placed to address your concerns.
The BNF is a joint publication of the 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.
Your sincerely, Chief Executive
The Royal College of Physicians will discuss this case at their next Patient Safety Committee and Joint Medicines Safety Working Group to explore whether further action is needed. They also clarified that the BNF does not list specific interactions for the cited drug combination, and that commercial prescribing software is not currently regulated to flag all theoretical compound effects.
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Dear Mr Walker,
The Royal College of Physicians (RCP) notes with concern the content of the Regulation 28 report for the prevention of future deaths related to the death of Chloe Elizabeth Burgess. We send our sincere condolences to the family of Ms Burgess.
This regulation 28 report is addressed to the RCP, and we have consulted cardiovascular and pharmacology experts, as well as liaising with the Royal Pharmaceutical Society to appropriately respond.
We note the matters of concern raised in this report, particularly that the potential dangers of the combination of amitriptyline, paroxetine and ivabradine are not widely appreciated and do not trigger an alert on the prescribing software used in primary care and/or by pharmacists. We also note that Chloe was known to have an electrical conducting abnormality of the heart, left bundle branch block an intraventricular conduction defect, which is in the BNF, lists as a ‘caution’ with the use of Ivabradine. Ivabradine | Drugs | BNF | NICE.
Our experts noted that whist ivabradine is a pacemaker current (If) inhibitor, used for the symptomatic management of heart-related chest pain and heart failure, it is also used for inappropriate sinus tachycardia.
We note that neither paroxetine or amitriptyline are listed as drugs interacting with ivabradine in the BNF Ivabradine | Interactions | BNF | NICE. The BNF is the recommended
nationally used prescribing aid. This is often used as a reference source for prescribing software and is overseen by the joint formulary committee.
Interactions between drugs which increase the concentration of ivabradine are well recognised and do appear in the BNF. Pharmaceutical colleagues also note that Stockley’s Drug Interactions table, accessed via the Medicines Complete website does not show a “life- threatening or contraindicated combination” between amitriptyline and ivabradine. It does suggest, on a theoretical basis, that “dosage adjustment or close monitoring is needed” as “the risk of QT-interval prolongation with amitriptyline might be exacerbated by bradycardia caused by ivabradine. If concurrent use is unavoidable, monitor cardiac effects (e.g. heart rate) closely.”
We note your concerns regarding the potential dangers related to failure to metabolise amitriptyline which can, incrementally, lead to toxicity, and the need for those prescribing to have full understanding of the potential interactions. The interaction by which paroxetine is predicted to increase the concentration of amitriptyline is also well recognised and included in the BNF Amitriptyline | Interactions | BNF | NICE / Paroxetine | Interactions | BNF | NICE. Pharmacology colleagues consulted noted that ivabradine is metabolised by a different enzyme from amitriptyline and are not aware of it increasing the concentration of amitriptyline. As ivabradine slows the heart, they note that there is a theoretical risk of QT- interval prolongation (changes in the electrical coordination within the heart) with amitriptyline which might be exacerbated by bradycardia caused by ivabradine and may increase the likelihood of arrhythmias in drugs which increase the QT interval on the ECG. This is supported by ongoing research, referenced below1.
The Royal Pharmaceutical Society, as joint publishers of the BNF have advised that pharmacokinetic (drug metabolism) interactions are included within the BNF, but that all theoretical compound effects of combinations of medications through their mode of action cannot be included. Furthermore, prescribing software for primary care and pharmacies is provided by independent commercial organisations, who will choose which reference materials they use to inform alerts. This software and its application is currently not regulated.
It is the role of all prescribers to understand the overarching mechanisms of action of medicines they may prescribe, and where similar actions occur by more than one medicine, or might exacerbate pathology in individual patients, particular caution or monitoring should be instituted. It is important that they do not rely on prescribing software, but use recognised reference materials.
The Royal College of Physicians works closely with the Royal Pharmaceutical Society, the British Pharmacological Society and NHS England Chief Pharmacists. We will discuss this case at our next Patient Safety Committee and Joint Medicines Safety Working Group, to explore whether further action should be taken informed by this case.
1 hERG potassium channel blockade by the HCN channel inhibitor bradycardic agent ivabradine - PubMed hERG potassium channel inhibition by ivabradine requires channel gating - PubMed hERG potassium channel inhibition by ivabradine may contribute to QT prolongation and risk of torsades de pointes - PubMed
The Royal College of Physicians (RCP) notes with concern the content of the Regulation 28 report for the prevention of future deaths related to the death of Chloe Elizabeth Burgess. We send our sincere condolences to the family of Ms Burgess.
This regulation 28 report is addressed to the RCP, and we have consulted cardiovascular and pharmacology experts, as well as liaising with the Royal Pharmaceutical Society to appropriately respond.
We note the matters of concern raised in this report, particularly that the potential dangers of the combination of amitriptyline, paroxetine and ivabradine are not widely appreciated and do not trigger an alert on the prescribing software used in primary care and/or by pharmacists. We also note that Chloe was known to have an electrical conducting abnormality of the heart, left bundle branch block an intraventricular conduction defect, which is in the BNF, lists as a ‘caution’ with the use of Ivabradine. Ivabradine | Drugs | BNF | NICE.
Our experts noted that whist ivabradine is a pacemaker current (If) inhibitor, used for the symptomatic management of heart-related chest pain and heart failure, it is also used for inappropriate sinus tachycardia.
We note that neither paroxetine or amitriptyline are listed as drugs interacting with ivabradine in the BNF Ivabradine | Interactions | BNF | NICE. The BNF is the recommended
nationally used prescribing aid. This is often used as a reference source for prescribing software and is overseen by the joint formulary committee.
Interactions between drugs which increase the concentration of ivabradine are well recognised and do appear in the BNF. Pharmaceutical colleagues also note that Stockley’s Drug Interactions table, accessed via the Medicines Complete website does not show a “life- threatening or contraindicated combination” between amitriptyline and ivabradine. It does suggest, on a theoretical basis, that “dosage adjustment or close monitoring is needed” as “the risk of QT-interval prolongation with amitriptyline might be exacerbated by bradycardia caused by ivabradine. If concurrent use is unavoidable, monitor cardiac effects (e.g. heart rate) closely.”
We note your concerns regarding the potential dangers related to failure to metabolise amitriptyline which can, incrementally, lead to toxicity, and the need for those prescribing to have full understanding of the potential interactions. The interaction by which paroxetine is predicted to increase the concentration of amitriptyline is also well recognised and included in the BNF Amitriptyline | Interactions | BNF | NICE / Paroxetine | Interactions | BNF | NICE. Pharmacology colleagues consulted noted that ivabradine is metabolised by a different enzyme from amitriptyline and are not aware of it increasing the concentration of amitriptyline. As ivabradine slows the heart, they note that there is a theoretical risk of QT- interval prolongation (changes in the electrical coordination within the heart) with amitriptyline which might be exacerbated by bradycardia caused by ivabradine and may increase the likelihood of arrhythmias in drugs which increase the QT interval on the ECG. This is supported by ongoing research, referenced below1.
The Royal Pharmaceutical Society, as joint publishers of the BNF have advised that pharmacokinetic (drug metabolism) interactions are included within the BNF, but that all theoretical compound effects of combinations of medications through their mode of action cannot be included. Furthermore, prescribing software for primary care and pharmacies is provided by independent commercial organisations, who will choose which reference materials they use to inform alerts. This software and its application is currently not regulated.
It is the role of all prescribers to understand the overarching mechanisms of action of medicines they may prescribe, and where similar actions occur by more than one medicine, or might exacerbate pathology in individual patients, particular caution or monitoring should be instituted. It is important that they do not rely on prescribing software, but use recognised reference materials.
The Royal College of Physicians works closely with the Royal Pharmaceutical Society, the British Pharmacological Society and NHS England Chief Pharmacists. We will discuss this case at our next Patient Safety Committee and Joint Medicines Safety Working Group, to explore whether further action should be taken informed by this case.
1 hERG potassium channel blockade by the HCN channel inhibitor bradycardic agent ivabradine - PubMed hERG potassium channel inhibition by ivabradine requires channel gating - PubMed hERG potassium channel inhibition by ivabradine may contribute to QT prolongation and risk of torsades de pointes - PubMed
Report Sections
Investigation and Inquest
On 19th September 2023 an investigation was commenced into the death of Chloe Elizabeth Burgess. The investigation concluded at the end of the inquest on 12th February 2025. The conclusion of the inquest was that the effect of medication in combination contributed to Chloe’s death.
Circumstances of the Death
Chloe Elizabeth Burgess was found deceased at home at Southampton, Hampshire on 8th September 2023. Chloe was prescribed heart medication after a diagnosis of sinus tachycardia and left bundle branch block as well as antidepressant medication. It is likely that the medication interacted with each other to raise the levels of amitriptyline in Chloe’s blood which, combined with her heart medication and an episode of sleep apnoea, induced severe cardiac arrhythmia and sudden cardiac death. She had been using the combination of drugs for four years before she died without concern. The potential dangers of the combination of drugs in Chloe’s case was not well-known or appreciated by those treating her. .
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Data sourced from Courts and Tribunals Judiciary under the Open Government Licence.