Department of Health and Social Care
Central Government
Action Planned
• The issue of monitoring blood plasma levels in people taking clozapine (or other antipsychotics) has been logged for consideration by the NICE guideline surveillance team undertaking the review process of clinical guideline CG178. (AI summary)
View full response
Dear Mr Haigh,
Thank you for your correspondence of 13 November to Matt Hancock about the death of Mr Thomas Jackson. I am replying as Minister with portfolio responsibility for medicines and I am grateful for the additional time in which to do so.
Firstly, I would like to say how sorry I was to read of the circumstances of Mr Jackson’s death. I appreciate his loss, at such a young age, must be extremely distressing for his family and loved ones and I offer my sincerest condolences.
It is essential that we look to make improvements where we can to ensure the safety of healthcare and prevent future deaths and I am grateful to you for bringing these matters to my attention.
My officials have made enquiries with a number of bodies on the matter of concern in your report that there should be routine therapeutic blood monitoring (testing of blood plasma levels) in patients who are prescribed clozapine.
I am advised that there is no national guidance that requires NHS trusts to undertake routine (six monthly or annual) monitoring of clozapine plasma levels. There is NICE guidance, ‘Psychosis and schizophrenia in adults: prevention and management’ (CG178)1, which supports the routine monitoring of the physical health of people prescribed antipsychotic medication (including clozapine).
1 https://www.nice.org.uk/guidance/cg178
I am informed that clinical guideline CG178 is to undergo a surveillance review to check whether it needs to be updated and given the concerns you raise, the issue of monitoring blood plasma levels in people taking clozapine (or other antipsychotics) has been logged for the consideration of the guideline surveillance team undertaking the review process.
As you may be aware, the Medicines and Healthcare products Regulatory Agency (MHRA), is responsible for the safety of medicines and medical devices. The MHRA seeks independent advice from the Commission on Human Medicines (CHM) which advises on whether the overall balance of benefits and risks of medicines is favourable at the time of licensing and remains so thereafter.
One of the ways in which the MHRA monitors the safety of licensed medications is through the Yellow Card scheme which receives information from both healthcare professionals and patients on side effects suspected to be associated with medicines. The concerns you have raised have been added to the MHRA’s adverse drug reaction database under Yellow Card reference number ADR 24386668-001.
Detailed guidance on the monitoring requirements for clozapine is provided in the authorised product information which consists of the Summary of Product Characteristics (SmPC) for prescribers and the Patient Information Leaflet which is supplied with each pack of medicine. The SmPC and PIL for clozapine can be found at mhra.gov.uk/spc-pil.
Currently, patient monitoring requirements for clozapine include the measurement of clinical parameters such as regular full blood counts; blood pressure; electrocardiograms; hepatic enzymes; blood sugar; lipids and weight. Therapeutic drug monitoring of blood plasma levels is not currently required under the terms of the clozapine marketing authorisation.
Individual NHS trusts might monitor clozapine drug levels based on clinical signs and symptoms to check compliance with treatment or as part of investigations into suspected toxicity but they are not required to routinely monitor therapeutic drug levels.
In light of the concerns you have raised, the MHRA has undertaken further investigation of the utility of drug monitoring in supporting safe use of clozapine and in doing so, has sought advice from the Pharmacovigilance Expert Advisory Group, which advises the Commission on Human Medicines. I am advised that further analysis of the available data is underway and further expert advice is being sought. The MHRA is happy to keep you informed on the progress of its assessment and I have asked that they do so with you directly.
Finally, I am informed that the national Medicine Safety Programme (MSP) is also aware of the issues concerning clozapine toxicity. The MSP is due to announce its initial priority areas in April 2019, and is currently in discussions as to whether to prioritise clozapine toxicity as a core component of the programme’s initial work to improve the safety of medication use across England.
I hope this reply is helpful.
NICOLA BLACKWOOD
Thank you for your correspondence of 13 November to Matt Hancock about the death of Mr Thomas Jackson. I am replying as Minister with portfolio responsibility for medicines and I am grateful for the additional time in which to do so.
Firstly, I would like to say how sorry I was to read of the circumstances of Mr Jackson’s death. I appreciate his loss, at such a young age, must be extremely distressing for his family and loved ones and I offer my sincerest condolences.
It is essential that we look to make improvements where we can to ensure the safety of healthcare and prevent future deaths and I am grateful to you for bringing these matters to my attention.
My officials have made enquiries with a number of bodies on the matter of concern in your report that there should be routine therapeutic blood monitoring (testing of blood plasma levels) in patients who are prescribed clozapine.
I am advised that there is no national guidance that requires NHS trusts to undertake routine (six monthly or annual) monitoring of clozapine plasma levels. There is NICE guidance, ‘Psychosis and schizophrenia in adults: prevention and management’ (CG178)1, which supports the routine monitoring of the physical health of people prescribed antipsychotic medication (including clozapine).
1 https://www.nice.org.uk/guidance/cg178
I am informed that clinical guideline CG178 is to undergo a surveillance review to check whether it needs to be updated and given the concerns you raise, the issue of monitoring blood plasma levels in people taking clozapine (or other antipsychotics) has been logged for the consideration of the guideline surveillance team undertaking the review process.
As you may be aware, the Medicines and Healthcare products Regulatory Agency (MHRA), is responsible for the safety of medicines and medical devices. The MHRA seeks independent advice from the Commission on Human Medicines (CHM) which advises on whether the overall balance of benefits and risks of medicines is favourable at the time of licensing and remains so thereafter.
One of the ways in which the MHRA monitors the safety of licensed medications is through the Yellow Card scheme which receives information from both healthcare professionals and patients on side effects suspected to be associated with medicines. The concerns you have raised have been added to the MHRA’s adverse drug reaction database under Yellow Card reference number ADR 24386668-001.
Detailed guidance on the monitoring requirements for clozapine is provided in the authorised product information which consists of the Summary of Product Characteristics (SmPC) for prescribers and the Patient Information Leaflet which is supplied with each pack of medicine. The SmPC and PIL for clozapine can be found at mhra.gov.uk/spc-pil.
Currently, patient monitoring requirements for clozapine include the measurement of clinical parameters such as regular full blood counts; blood pressure; electrocardiograms; hepatic enzymes; blood sugar; lipids and weight. Therapeutic drug monitoring of blood plasma levels is not currently required under the terms of the clozapine marketing authorisation.
Individual NHS trusts might monitor clozapine drug levels based on clinical signs and symptoms to check compliance with treatment or as part of investigations into suspected toxicity but they are not required to routinely monitor therapeutic drug levels.
In light of the concerns you have raised, the MHRA has undertaken further investigation of the utility of drug monitoring in supporting safe use of clozapine and in doing so, has sought advice from the Pharmacovigilance Expert Advisory Group, which advises the Commission on Human Medicines. I am advised that further analysis of the available data is underway and further expert advice is being sought. The MHRA is happy to keep you informed on the progress of its assessment and I have asked that they do so with you directly.
Finally, I am informed that the national Medicine Safety Programme (MSP) is also aware of the issues concerning clozapine toxicity. The MSP is due to announce its initial priority areas in April 2019, and is currently in discussions as to whether to prioritise clozapine toxicity as a core component of the programme’s initial work to improve the safety of medication use across England.
I hope this reply is helpful.
NICOLA BLACKWOOD