Recurring concern

Unreliable methotrexate safety information and guidance

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First reported 16 Nov 2022•Latest report 20 Feb 2026

Definition

What this concern includes

Includes failures in the dedicated methotrexate safety-information and guidance process, including review of patient literature after adverse effects, current dosing guidance, toxicity warnings, treatment-continuation or cessation advice, and clear responsibilities and referral routes among clinicians and pharmacists.

Not included

Excludes generic medication-guidance, patient-information or adverse-event-reporting deficiencies where methotrexate is not the material safety concern.
Excludes failures in administering, dispensing or monitoring methotrexate after current and clear safety guidance has been provided.
Excludes unrelated clinical conditions, medicines and treatment pathways without a direct methotrexate safety-information or guidance connection.

Reports: 2
Individual concerns: 4
Date range: 2022–2026
Stated actions: 3

Reports over time

Reports about this concern issued each year.

* 2026 is projected from reports observed to 7 Sep 2026.

Most frequent recipients

Reports about this concern sent to each recipient.

Greater Manchester Medicines Management Group1

NHS England1

Concerns and responses across reports

Only concerns grouped under this recurring concern are included. Select any concern, action or position to view the source wording.

20 Feb2026
Cheshire
Concerns raised2
1. Failure of the methotrexate guideline to provide a current therapeutic initial dose
2. Failure of the methotrexate guideline to define current responsibilities and direct patients to the appropriate healthcare professional
Responses linked to these concerns
Each statement is shown once, even when linked to more than one concern.
Actions described in response 3
1. Action
  Continue making urgent safety amendments to shared care protocols through clinical governance processes.
  Stated by NHS Greater Manchester Integrated Care BoardStated in progress
2. Action
  Review monitoring requirements and dosing wording in the shared care protocol against contemporary rheumatology guidance.
  Stated by NHS Greater Manchester Integrated Care BoardStated planned
3. Action
  Consider clarifying in the guideline who patients should contact when they develop concerning symptoms.
  Stated by NHS Greater Manchester Integrated Care BoardStated planned
Respondent positions 3
1. Position
  The methotrexate protocol’s dose range reflects current product information and guidance, with lower initial dosing supporting safety and specialist adjustment.
  Stated by NHS Greater Manchester Integrated Care BoardDisputes the concern
1. Position
  Patients with possible methotrexate toxicity should be assessed by their GP or specialist team, not community pharmacists.
  Stated by NHS Greater Manchester Integrated Care BoardRedirects responsibility
2. Position
  The patient was ineligible for Pharmacy First, so the service should not have managed the patient in this case.
  Stated by NHS Greater Manchester Integrated Care BoardDisputes the concern
AI-generated summary

Alan CRABTREE · Prevention of Future Deaths report

This summary was generated using AI from the published report. Please read the original report for the complete account.

Report summary

Alan Crabtree was prescribed methotrexate on 3 February 2025, developed rapid-onset pancytopenia, was admitted to hospital on 18 February, and died of pneumonia on 1 March 2025. The report identified concerns that the methotrexate dosing guidance was outdated and that its advice about which healthcare professional patients should contact for signs of toxicity was ambiguous, potentially delaying appropriate treatment.

Read the report on judiciary.uk
Source evidence
How this individual concern was interpreted
PFD Monitor created a concise, searchable interpretation from the report wording shown below.
PFD Monitor interpretation
Failure of the methotrexate guideline to provide a current therapeutic initial dose
Wider context from the report
“1. The dose regime referred to in the “Shared Care Guideline for Oral Methotrexate in Rheumatological Conditions in Adults” does not reflect current practice and the initial dose recommended is a sub-therapeutic dose. ”
Source location
Alan CRABTREE · Prevention of Future Deaths report
Page 2 · concerns
Open source report
Source evidence
How this individual concern was interpreted
PFD Monitor created a concise, searchable interpretation from the report wording shown below.
PFD Monitor interpretation
Failure of the methotrexate guideline to define current responsibilities and direct patients to the appropriate healthcare professional
Wider context from the report
“2. The “Shared Care Guideline for Oral Methotrexate in Rheumatological Conditions in Adults” was produced in September 2017. Since then, the “Pharmacy First” scheme has come into effect. The guidance therefore does not reflect the changes in the relevant responsibilities between secondary care, GPs and community pharmacists leading to ambiguity as to what type of healthcare professional a patient should consult and potentially fatal delay in ceasing methotrexate or commencing treatment for toxicity for the same. ”
Source location
Alan CRABTREE · Prevention of Future Deaths report
Page 2 · concerns
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
Continue making urgent safety amendments to shared care protocols through clinical governance processes.

Verbatim wording from the response
“• Continue to make urgent safety-related amendments through existing clinical governance processes where required.”

Source location
2026-0103 - Response from Greater Manchester Integrated Care
Page 2 · response
Published 24 February 2026
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
Review monitoring requirements and dosing wording in the shared care protocol against contemporary rheumatology guidance.

Verbatim wording from the response
“There has been a recent update to specialist guidance to methotrexate monitoring, following publication of the British Society for Rheumatology guideline in 2025. National medicines information resources, including guidance published by the Specialist Pharmacy Service, have not yet fully updated their publicly available monitoring guidance to reflect these newer recommendations. In response to these developments, a review of the monitoring requirements within the Shared Care Protocol has already been scheduled, and the dosing wording will also be reviewed as part of the next update of the protocol to ensure alignment with contemporary rheumatology practice and national guidance.”

Source location
2026-0103 - Response from Greater Manchester Integrated Care
Page 2 · response
Published 24 February 2026
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
Consider clarifying in the guideline who patients should contact when they develop concerning symptoms.

Verbatim wording from the response
“As part of the planned review, NHS Greater Manchester will consider whether the guidelines could be clearer for patients about who to contact if they develop concerning symptoms.”

Source location
2026-0103 - Response from Greater Manchester Integrated Care
Page 3 · response
Published 24 February 2026
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
The methotrexate protocol’s dose range reflects current product information and guidance, with lower initial dosing supporting safety and specialist adjustment.

Verbatim wording from the response
“The Shared Care Protocol (SCP) includes a section that explains how methotrexate doses should be managed once a hospital specialist has started treatment. It sets out a range of doses that may be used, starting at a lower dose and increasing gradually over time. The protocol states that methotrexate should be prescribed at 7.5–25 mg once weekly according to hospital instructions, with an initial dose of 5–15 mg once weekly, titrated upwards by 2.5–5 mg every 2–6 weeks according to response, with a typical maintenance dose up to 20 mg per week, and in some circumstances up to 25 mg per week. The protocol also specifies that only 2.5 mg tablets should be prescribed, which is a recognised national safety measure intended to minimise the risk of dosing errors with methotrexate.”

Source location
2026-0103 - Response from Greater Manchester Integrated Care
Page 1 · response
Published 24 February 2026
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
Patients with possible methotrexate toxicity should be assessed by their GP or specialist team, not community pharmacists.

Verbatim wording from the response
“The SCP clearly advises patients taking methotrexate to seek medical advice if they develop symptoms such as sore throat or mouth ulcers, as these can be signs of serious side effects. Patients are directed to contact their GP or specialist team, who are responsible for their ongoing care and monitoring.”

Source location
2026-0103 - Response from Greater Manchester Integrated Care
Page 3 · response
Published 24 February 2026
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
The patient was ineligible for Pharmacy First, so the service should not have managed the patient in this case.

Verbatim wording from the response
“We believe there is a clear need to provide feedback to NHS England, as the commissioner of the Pharmacy First Service, to highlight the wider challenges associated with the delivery of the service. The PDF report review has identified that the patient should not have been managed through the Pharmacy First Service, as they did not meet the eligibility criteria for this service. This highlights the need for strengthened pathway exclusions and clearer safeguards to ensure that patients with complex clinical needs or specialist oversight requirements are appropriately identified and excluded from Pharmacy First pathways.”

Source location
2026-0103 - Response from Greater Manchester Integrated Care
Page 4 · response
Published 24 February 2026
Open published response
16 Nov2022
Liverpool and the Wirral
Concerns raised2
1. Unclear criteria for reviewing patient literature after reports of methotrexate phototoxicity
2. Failure to include methotrexate phototoxicity in literature given to patients
Responses linked to these concerns
Each statement is shown once, even when linked to more than one concern.

No linked response statements
No respondent-stated action or position is linked to these concerns in the published data.
AI-generated summary

Susan Elizabeth SKILLEN · Prevention of Future Deaths report

This summary was generated using AI from the published report. Please read the original report for the complete account.

Report summary

Susan Elizabeth Skillen, aged 61, was admitted to hospital on 26 May 2022 after being found at home with reduced consciousness, low blood pressure, hypoglycaemia and severe neutropenia, and died later that day. The inquest concluded that she died from neutropenic sepsis, with skin loss associated with phototoxicity considered the most likely source of infection and the combined effects of sun exposure and rheumatoid arthritis medication contributing. The substantive concern was that phototoxicity is an extremely rare side effect of methotrexate but did not appear in the literature provided to patients, and it was unclear whether the patient literature required review.

Read the report on judiciary.uk
Source evidence
How this individual concern was interpreted
PFD Monitor created a concise, searchable interpretation from the report wording shown below.
PFD Monitor interpretation
Unclear criteria for reviewing patient literature after reports of methotrexate phototoxicity
Wider context from the report
“Phototoxicity is an extremely rare side effect of methotrexate but does not appear in literature given to patients. The hospital were requested to complete the Yellow Card system but it was unclear if the literature for patients needed to be reviewed depending upon how many other patients had suffered this side effect. ”
Source location
Susan Elizabeth SKILLEN · Prevention of Future Deaths report
Page 2 · concerns
Open source report
Source evidence
How this individual concern was interpreted
PFD Monitor created a concise, searchable interpretation from the report wording shown below.
PFD Monitor interpretation
Failure to include methotrexate phototoxicity in literature given to patients
Wider context from the report
“Phototoxicity is an extremely rare side effect of methotrexate but does not appear in literature given to patients. The hospital were requested to complete the Yellow Card system but it was unclear if the literature for patients needed to be reviewed depending upon how many other patients had suffered this side effect. ”
Source location
Susan Elizabeth SKILLEN · Prevention of Future Deaths report
Page 2 · concerns
Open source report

Data last updated 7 September 2026

What this concern includes

Not included

Reports over time

Concerns raised2

Failure of the methotrexate guideline to provide a current therapeutic initial dose

Failure of the methotrexate guideline to define current responsibilities and direct patients to the appropriate healthcare professional

Actions described in response An action is something a respondent says it has done, is doing, or plans to do in response to the concern raised.3

Respondent positions A position is what a respondent says about the concern when they do not describe a specific action.3

Concerns raised2

Unclear criteria for reviewing patient literature after reports of methotrexate phototoxicity

Failure to include methotrexate phototoxicity in literature given to patients

Actions described in response 3

Respondent positions 3