PFD report

Sean Benjamin CRAWFORD · Prevention of Future Deaths report

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Issued 15 Feb 2024•County Durham and Darlington

Report record

Published report and response evidence

This page connects the concerns raised in this report with statements found in recipients’ published responses. A link shows a clear evidence connection; it does not assign responsibility.

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Concerns
2

Raised in this report

Recipients
3

Named on the report

Responses found
3

Of 3 recipients

Stated actions
9

Described in responses

Recipients and published responses

Source document

Full report text

This is the full text from the original published report.

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Concerns and recipient responses

Select any concern, action or position to view the source wording.

Concerns raised2

  1. Failure of clozapine packaging and leaflets to warn that combined use with alcohol may cause death
    Part of recurring concern: Inadequate controls for combined sedative medication toxicityPart of recurring concern: Inadequate safety warnings on medication packagingPart of recurring concern: Unreliable safety monitoring and guidance for clozapine treatment
  2. Lack of guidance on the risk of death from combined clozapine and alcohol use
    Part of recurring concern: Inadequate controls for combined sedative medication toxicityPart of recurring concern: Unreliable safety monitoring and guidance for clozapine treatment
Responses linked to these concerns

Each statement is shown once, even when linked to more than one concern.

Actions described in response An action is something a recipient says it has done, is doing, or plans to do in response to a concern raised.5

  1. Action

    Work with the British National Formulary as the clozapine assessment progresses.

    Stated by Medicines and Healthcare products Regulatory AgencyStated plannedThe respondent said that this action was planned when they made their response on 22 February 2024.
  2. Action

    Conduct a further assessment of clozapine product information on drug-drug interactions and consider improvements for healthcare professionals, patients, families and carers.

    Stated by Medicines and Healthcare products Regulatory AgencyStated plannedThe respondent said that this action was planned when they made their response on 22 February 2024.
  3. Action

    Add pharmacodynamic interaction tables to online BNF and BNFC versions.

    Stated by BNF PublicationsStated completedThe respondent said that this action was complete when they made their response on 22 February 2024.

Respondent positions A position is what a recipient says about a concern when it does not describe a specific action.2

  1. Position

    NICE is responsible for considering whether the report’s findings should affect published guidance on clozapine and alcohol risks.

    Stated by Department of Health and Social CareRedirects responsibilityThe respondent said that another organisation was responsible for deciding or taking action.

Source evidence

How this individual concern was interpreted

PFD Monitor created a concise, searchable interpretation from the report wording shown below. Response links show a clear evidence connection; they do not assign responsibility.

PFD Monitor interpretation

Failure of clozapine packaging and leaflets to warn that combined use with alcohol may cause death

Wider context from the report

“The circumstances in which Sean came by his death, the combined effects of clozapine with alcohol, seems to be, statistically, very rare. None of the professionals who gave evidence in this case could cite a death with the same cause of death as that suffered by Sean. This said, clozapine is a well-established medication whose side effects are well known. It was originally developed in the 1960s. It is well-known that it requires careful management and monitoring. The side effects are recognised ones and widely known. None of the professional witnesses expressed any lack of familiarity with it or its side effects. One of these side effects is sedation. Likewise, obviously, alcohol is a recognised central nervous system depressant. This is a death from Central Nervous System Depression, consequent to a comparatively high level of clozapine and a comparatively high level of ethanol in the blood – neither individually fatal. It is evident that there is no guidance in any academic literature, British National Formulary, or NICE or MHRA advices on the dangers of death in this scenario. It is noticeable that the leaflet that comes with the Clozaril (clozapine) packages clearly states that it must not be taken with alcohol, and the evidence to me was that the medication comes with a further label, in a similar vein, on the packaging. Neither, however, advises of death being a possibility. All the literature advises that sedation is a potentially dangerous side effect of clozapine. Death from Central Nervous System Depression, over-sedation, is not uncommon. It is often associated with alcohol, and other substance, use. ”

Is this part of a recurring concern?

Yes — Inadequate controls for combined sedative medication toxicity; Inadequate safety warnings on medication packaging; Unreliable safety monitoring and guidance for clozapine treatment.

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Source evidence

How this individual concern was interpreted

PFD Monitor created a concise, searchable interpretation from the report wording shown below. Response links show a clear evidence connection; they do not assign responsibility.

PFD Monitor interpretation

Lack of guidance on the risk of death from combined clozapine and alcohol use

Wider context from the report

“The circumstances in which Sean came by his death, the combined effects of clozapine with alcohol, seems to be, statistically, very rare. None of the professionals who gave evidence in this case could cite a death with the same cause of death as that suffered by Sean. This said, clozapine is a well-established medication whose side effects are well known. It was originally developed in the 1960s. It is well-known that it requires careful management and monitoring. The side effects are recognised ones and widely known. None of the professional witnesses expressed any lack of familiarity with it or its side effects. One of these side effects is sedation. Likewise, obviously, alcohol is a recognised central nervous system depressant. This is a death from Central Nervous System Depression, consequent to a comparatively high level of clozapine and a comparatively high level of ethanol in the blood – neither individually fatal. It is evident that there is no guidance in any academic literature, British National Formulary, or NICE or MHRA advices on the dangers of death in this scenario. It is noticeable that the leaflet that comes with the Clozaril (clozapine) packages clearly states that it must not be taken with alcohol, and the evidence to me was that the medication comes with a further label, in a similar vein, on the packaging. Neither, however, advises of death being a possibility. All the literature advises that sedation is a potentially dangerous side effect of clozapine. Death from Central Nervous System Depression, over-sedation, is not uncommon. It is often associated with alcohol, and other substance, use. ”

Is this part of a recurring concern?

Yes — Inadequate controls for combined sedative medication toxicity; Unreliable safety monitoring and guidance for clozapine treatment.

Open source report

Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Work with the British National Formulary as the clozapine assessment progresses.

Verbatim wording from the response

“We are aware that you have also written to the BNF, and we will work with them as our assessment progresses. In the meantime, we will continue to closely monitor the safety of clozapine, including cases of drug-drug interactions. Should any updates to the product information be required we will issue an article in our bulletin to healthcare professionals “Drug Safety Update” accordingly.”

Source location

Response from Medicine and Healthcare products Regulatory Agency
Page 2 · response
Published 22 February 2024

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Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Conduct a further assessment of clozapine product information on drug-drug interactions and consider improvements for healthcare professionals, patients, families and carers.

Verbatim wording from the response

“We have considered the evidence provided and the circumstances leading to Mr Crawford’s death. We have also recently met with a member of Mr Crawford’s immediate family to discuss their concerns. Some of these relate to clinical discussions between a patient and their prescriber which we are not able to address, as it is not within our remit to comment on the clinical care in specific cases. However, because of the nature of some of the concerns raised, we intend to conduct a further assessment of the information provided within the clozapine product information regarding drug-drug interactions. As part of this assessment, we will be giving careful consideration to the information which is provided to healthcare professionals, patients and their families and carers, and whether this can be improved.”

Source location

Response from Medicine and Healthcare products Regulatory Agency
Page 2 · response
Published 22 February 2024

Open published response

Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Add pharmacodynamic interaction tables to online BNF and BNFC versions.

Verbatim wording from the response

“The BNF includes information on pharmacodynamic interactions, that is interactions between drugs which have similar or antagonistic pharmacological effects or side-effects. This information is present within interaction messages of relevant drug monographs in online versions of the BNF and the BNF app. The same information is presented in tables in print editions of the BNF, but at the time of this death, these tables were not present in online versions of the BNF or in the BNF + BNFC app.”

Source location

Response from BNF
Page 1 · response
Published 22 February 2024

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Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Review and revise pharmacodynamic interaction wording on sedative and CNS-depressant risks in BNF messages and tables.

Verbatim wording from the response

“To address the concerns raised in your report, we plan to review the wording around the use of drugs that cause sedation (including clozapine and alcohol) and drugs with CNS depressant effects (including alcohol) within the pharmacodynamic interaction messages and in the tables. This will further highlight that concurrent use of two or more drugs that can cause sedation and / or CNS depression might increase the risk of CNS depressant effects, such as sedation, unconsciousness, coma, respiratory depression, and cardiovascular depression, and / or enhance the effects of drugs with CNS depressant effects. In addition, the pharmacodynamic interaction tables have now been added to the online versions of the BNF and BNFC ensuring this content is more accessible to users.”

Source location

Response from BNF
Page 1 · response
Published 22 February 2024

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Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Share the coroner’s report with NICE for consideration of its findings in published guidance.

Verbatim wording from the response

“should not be taken due to the potential harm to the patient. Departmental officials, however, have shared your report with NICE, so it can consider the impact of your findings on its published guidance.”

Source location

Response from Department of Health and Social Care
Page 2 · response
Published 22 February 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

NICE is responsible for considering whether the report’s findings should affect published guidance on clozapine and alcohol risks.

Verbatim wording from the response

“In preparing this response, Departmental officials have made enquiries with National Institute for Health and Care Excellence (NICE). The National Institute for Health and Care Excellence (NICE) is the independent body responsible for developing authoritative, evidence-based guidance on best practice for the health and care system. NICE guidelines are developed by experts based on a thorough assessment of the available evidence and through extensive engagement with stakeholders. Healthcare professionals are expected to take them into full account in their decision making, although it is important to note that NICE guidelines are not mandatory and do not override a clinician’s responsibility to make decisions appropriate to individual patients.”

Source location

Response from Department of Health and Social Care
Page 1 · response
Published 22 February 2024

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Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

MHRA is responsible for assessing and potentially improving clozapine product information about drug interactions and associated safety risks.

Verbatim wording from the response

“I am aware that the Medicines & Healthcare products Regulatory Agency (MHRA) has provided a response in respect of the key concern you raise in the report. As you will be aware, MHRA is an 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 reported to occur with use of a medicine are appropriately described in the authorised product information. However, MHRA has recognised in the response that none of the authorised product information specifically mention any risk of death because of the interaction with alcohol.”

Source location

Response from Department of Health and Social Care
Page 2 · response
Published 22 February 2024

Open published response

Other statements in published responses

These actions and other statements could not be clearly connected to one concern in this report.

Recipient-stated actions An action is something a recipient says it has done, is doing, or plans to do in response to a concern raised.4

  1. 1

    Continue closely monitoring clozapine safety, including drug-drug interaction cases.

    Stated by Medicines and Healthcare products Regulatory AgencyStated completedThe respondent said that this action was complete when they made their response on 22 February 2024.
  2. 2

    Engage relevant stakeholders during the clozapine product-information assessment to address their concerns.

    Stated by Medicines and Healthcare products Regulatory AgencyStated plannedThe respondent said that this action was planned when they made their response on 22 February 2024.
  3. 3

    Complete a wider review of clozapine incorporating the product-information assessment.

    Stated by Medicines and Healthcare products Regulatory AgencyStated plannedThe respondent said that this action was planned when they made their response on 22 February 2024.
  4. 4

    Work with the MHRA to reflect relevant future MHRA updates in the BNF.

    Stated by BNF PublicationsStated in progressThe respondent said that this action was in progress when they made their response on 22 February 2024.

Recipient positions A position is what a recipient says about a concern when they do not describe a specific action.1

  1. 1

    Commenting on clinical care in specific cases is outside the remit, so those concerns cannot be addressed.

    Stated by Medicines and Healthcare products Regulatory AgencyOutside remitThe respondent said that this matter was outside its role or authority.

Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Continue closely monitoring clozapine safety, including drug-drug interaction cases.

Verbatim wording from the response

“We are aware that you have also written to the BNF, and we will work with them as our assessment progresses. In the meantime, we will continue to closely monitor the safety of clozapine, including cases of drug-drug interactions. Should any updates to the product information be required we will issue an article in our bulletin to healthcare professionals “Drug Safety Update” accordingly.”

Source location

Response from Medicine and Healthcare products Regulatory Agency
Page 2 · response
Published 22 February 2024

Open published response

Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Engage relevant stakeholders during the clozapine product-information assessment to address their concerns.

Verbatim wording from the response

“We intend to engage with relevant stakeholders during this process to ensure that their concerns are addressed. This assessment will be considered as part of a wider review of clozapine which will be completed this year.”

Source location

Response from Medicine and Healthcare products Regulatory Agency
Page 2 · response
Published 22 February 2024

Open published response

Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Complete a wider review of clozapine incorporating the product-information assessment.

Verbatim wording from the response

“We intend to engage with relevant stakeholders during this process to ensure that their concerns are addressed. This assessment will be considered as part of a wider review of clozapine which will be completed this year.”

Source location

Response from Medicine and Healthcare products Regulatory Agency
Page 2 · response
Published 22 February 2024

Open published response

Source evidence

How this respondent action was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Work with the MHRA to reflect relevant future MHRA updates in the BNF.

Verbatim wording from the response

“We are aware that your report has also been sent to the MHRA. We have been in touch with the MHRA, and will work together to ensure that any updates from the MHRA are reflected in the BNF where appropriate.”

Source location

Response from BNF
Page 2 · response
Published 22 February 2024

Open published response

Source evidence

How this respondent position was interpreted

PFD Monitor created a concise, searchable interpretation from the published response wording shown below.

PFD Monitor interpretation

Commenting on clinical care in specific cases is outside the remit, so those concerns cannot be addressed.

Verbatim wording from the response

“We have considered the evidence provided and the circumstances leading to Mr Crawford’s death. We have also recently met with a member of Mr Crawford’s immediate family to discuss their concerns. Some of these relate to clinical discussions between a patient and their prescriber which we are not able to address, as it is not within our remit to comment on the clinical care in specific cases. However, because of the nature of some of the concerns raised, we intend to conduct a further assessment of the information provided within the clozapine product information regarding drug-drug interactions. As part of this assessment, we will be giving careful consideration to the information which is provided to healthcare professionals, patients and their families and carers, and whether this can be improved.”

Source location

Response from Medicine and Healthcare products Regulatory Agency
Page 2 · response
Published 22 February 2024

Open published response
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Information checked against the published report and official responses · Data reviewed 7 Sep 2026 · About data quality and limitations

Data last updated 7 September 2026