The Medicines and Healthcare products Regulatory Agency (MHRA) confirms that in June 2026, the Neurology, Pain and Psychiatry Expert Advisory Group (NPPEAG) considered an assessment of clozapine drug level monitoring. The NPPEAG provided advice about the requirements for this type of monitoring. At present, clozapine drug-level monitoring is required only in specific clinical situations, partly because of the high level of variability between patients. The MHRA is taking forward the NPPEAG’s recommendations and will communicate to healthcare professionals once the regulatory position is finalised.

The review of clozapine drug-level monitoring focused on clinical and scientific data to establish the value of this type of monitoring in clinical practice. It took into account a range of information, including overall reporting patterns and themes in reports received through the Yellow Card scheme, but did not include clinical review of individual Yellow Card reports. MHRA safety assessments may also consider the views of patients and other stakeholders.

The MHRA will be launching a survey in the summer to gather information on awareness of key risks associated with clozapine, and to assess whether additional measures would be helpful for patients, their families, and carers, as well as healthcare professionals involved in the care of patients receiving clozapine.

The Medicines and Healthcare products Regulatory Agency (MHRA) confirms that in June 2026, the Neurology, Pain and Psychiatry Expert Advisory Group (NPPEAG) considered an assessment of clozapine drug level monitoring. The NPPEAG provided advice about the requirements for this type of monitoring. At present, clozapine drug-level monitoring is required only in specific clinical situations, partly because of the high level of variability between patients. The MHRA is taking forward the NPPEAG’s recommendations and will communicate to healthcare professionals once the regulatory position is finalised.

The review of clozapine drug-level monitoring focused on clinical and scientific data to establish the value of this type of monitoring in clinical practice. It took into account a range of information, including overall reporting patterns and themes in reports received through the Yellow Card scheme, but did not include clinical review of individual Yellow Card reports. MHRA safety assessments may also consider the views of patients and other stakeholders.

The MHRA will be launching a survey in the summer to gather information on awareness of key risks associated with clozapine, and to assess whether additional measures would be helpful for patients, their families, and carers, as well as healthcare professionals involved in the care of patients receiving clozapine.

Decisions about whether to prescribe clozapine, including when it should be considered in a patient’s treatment pathway, are matters for the clinician responsible for a patient’s care. Prescribers are expected to take full account of individual clinical circumstances and to use their professional judgement in determining the most appropriate treatment.

Clinicians are supported by national guidance, including from the National Institute for Health and Care Excellence (NICE), on using clozapine for treatment-resistant schizophrenia. NICE keeps this guidance under review so it stays up to date. Anyone taking clozapine must have regular blood tests, including checks on white blood cells, neutrophils and platelets. This is because, in rare cases, clozapine can cause serious and potentially fatal blood problems.

Training, education, and awareness for clinicians are led locally by National Health Service organisations and informed by national clinical guidance. The Royal College of Psychiatrists has also produced training on the Wim’s Protocol, which was created to support improvement in clinician training and awareness around clozapine use. Further information on the Wim’s Protocol is available at the following link:

https://elearninghub.rcpsych.ac.uk/products/Wims_protocol

Patients are central to decisions about their care. Clinicians should work with patients and, where appropriate, their carers and families to support shared decision-making, including discussing the benefits and risks of treatment options and tailoring care to individual needs and preferences.

NHS England is finalising guidance for mental health services to strengthen the involvement of families, carers, and support networks in planning and delivering care for people with severe mental health problems. The Mental Health Personalised Care Framework will help services deliver effective personalised care.

No specific assessment has been made of the reliability of current systems for transporting and processing serum Clozapine blood samples across National Health Service providers. Operational responsibility for the collection, transport, and processing of clozapine blood samples lies with individual NHS providers and their commissioned pathology and courier services. Further information on sample type and transport stability is available via individual NHS trust laboratory webpages.

Testing for clozapine levels is carried out within the same accredited pathology framework used for other biochemical assays, with defined requirements for sample collection, labelling, storage and transport to maintain sample integrity. Laboratories providing clozapine assays hold UKAS ISO 15189 accreditation and are required to undertake internal quality control and participate in national External Quality Assessment schemes to ensure accuracy and reproducibility of results.

Samples are transported through contracted courier services operating temperature controlled logistics, chain of custody processes and turnaround time requirements. These arrangements form part of routine clinical governance, incident reporting and performance management across NHS pathology services to prevent sample loss and provide assurance on the reliability of testing. Detailed operational arrangements are managed locally by individual pathology providers.

No specific assessment has been made of the reliability of current systems for transporting and processing serum Clozapine blood samples across National Health Service providers. Operational responsibility for the collection, transport, and processing of clozapine blood samples lies with individual NHS providers and their commissioned pathology and courier services. Further information on sample type and transport stability is available via individual NHS trust laboratory webpages.

Testing for clozapine levels is carried out within the same accredited pathology framework used for other biochemical assays, with defined requirements for sample collection, labelling, storage and transport to maintain sample integrity. Laboratories providing clozapine assays hold UKAS ISO 15189 accreditation and are required to undertake internal quality control and participate in national External Quality Assessment schemes to ensure accuracy and reproducibility of results.

Samples are transported through contracted courier services operating temperature controlled logistics, chain of custody processes and turnaround time requirements. These arrangements form part of routine clinical governance, incident reporting and performance management across NHS pathology services to prevent sample loss and provide assurance on the reliability of testing. Detailed operational arrangements are managed locally by individual pathology providers.

NHS England’s National Patient Safety Team collect records of all patient safety incidents recorded by National Health Service trusts via the Learn From Patient Safety Events service. These records are used to identify new and under-recognised risks to patient safety and to understand themes and trends. The insight generated informs work to improve patient safety across the NHS. Further information is available at the following link:

https://www.england.nhs.uk/patient-safety/patient-safety-insight/learning-from-patient-safety-events/using-patient-safety-events-data-to-keep-patients-safe/#

The safety of clozapine is kept under continual review by the Medicines and Healthcare products Regulatory Agency (MHRA) using a number of data sources, including reports of suspected side effects through the Yellow Card Scheme, data from marketing authorisation holders, and research published in the scientific literature.

Each clozapine marketing authorisation holder operates a Patient Monitoring Scheme which focuses on the blood monitoring requirements for clozapine. However, regular contact with healthcare professionals caring for patients receiving clozapine has resulted in a high proportion of suspected side effects being reported through the Yellow Card scheme. These reports are published by the MHRA in the interactive drug analysis profile for clozapine, with further information available at the following link:

https://yellowcard.mhra.gov.uk/idaps/CLOZAPINE

The Summary of Product Characteristics for clozapine outlines the monitoring requirements needed to minimise the risks of possible side effects for healthcare professionals. However, the MHRA does not regulate clinical practice or audit NHS record-keeping systems.

Clozapine is used to treat people with schizophrenia in whom other medicines have not worked. It is also used to treat severe disturbances in the thoughts, emotions, and behaviour of people with Parkinson’s disease in whom other medicines have not worked.

The known side effects of clozapine are outlined in the product information, the Summary of Product Characteristics (SPC) for healthcare professionals, and the Patient Information Leaflet which is provided in each pack of the medicine. The SPC states that clozapine should be stopped in a number of clinical situations including after developing a low white blood cell count, fever above 38^oC, high blood glucose, also known as hyperglycaemia, as well as jaundice or clinically relevant increases in liver enzymes. If clozapine is restarted it must be carefully titrated and monitoring requirements followed.

Inadvertent withdrawal of clozapine is an issue that is included in the National Health Service’s Time Critical Medicines Safety Improvement Programme, with further information available at the following link:

https://www.sps.nhs.uk/articles/safer-use-of-time-critical-medicines-programme/

The programme is supporting over 50 NHS hospitals to improve the reliability of administration of Time Critical Medicines such as clozapine.

In July 2024 a thematic review of clozapine safety conducted in the North West of England was shared with the NHS England National Medication Safety Officer Network. This included a range of clozapine safety resources published online, such as:

- Managing the risks associated with patients prescribed clozapine, which is available at the following link:
https://www.sps.nhs.uk/articles/managing-the-risks-associated-with-patients-prescribed-clozapine/;

- Clinical considerations for patients prescribed clozapine, which is available at the following link:
https://www.sps.nhs.uk/articles/clinical-considerations-for-patients-prescribed-clozapine/;

- Managing constipation in people taking clozapine, which is available at the following link:
https://www.sps.nhs.uk/articles/managing-constipation-in-people-taking-clozapine/;

- Clozapine use in adults with swallowing difficulties, which is available at the following link:
https://www.sps.nhs.uk/articles/clozapine-use-in-adults-with-swallowing-difficulties/;

- Managing specific interactions with smoking, which is available at the following link:
https://www.sps.nhs.uk/articles/managing-specific-interactions-with-smoking/; and

- Managing complexities of medication use across care boundaries, which includes a podcast on clozapine safety and which is available at the following link:
https://www.sps.nhs.uk/articles/managing-complexities-of-medication-use-across-care-boundaries/.

As with all medicines, the safety of clozapine is kept under continual review by the Medicines and Healthcare products Regulatory Agency (MHRA) using a number of data sources. The MHRA is currently reviewing the blood monitoring requirements associated with clozapine.

Clozapine is used to treat people with schizophrenia in whom other medicines have not worked and it is also used to treat severe disturbances in the thoughts, emotions, and behaviour of people with Parkinson’s disease in whom other medicines have not worked.

Clozapine is associated with potentially life threatening side effects including the risk of agranulocytosis. Patients must have regular blood tests to ensure their white blood cell count doesn’t drop too low which is classified as a red result. Clozapine may only be taken if the patient has a normal blood count.

As with all medicines, the safety of clozapine is kept under continual review by the Medicines and Healthcare products Regulatory Agency (MHRA) using a number of data sources including reports of suspected side effects through the Yellow Card Scheme, data from marketing authorisation holders, and research published in the scientific literature.

The MHRA is currently reviewing the blood monitoring requirements associated with clozapine, to ensure these continue to minimise the risk of agranulocytosis whilst allowing patients to access clozapine when needed. Currently, the product information for clozapine, including the summary of product characteristics states that patients must stop clozapine if a red result is obtained and that they should not be re-exposed to clozapine.

The Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines and medicinal products and ensures that the product information for each medicines reflects what is known about the medicine and provides information to support safe use and minimise risks. The product information consists of the Summary of Product Characteristics for healthcare professionals and the patient information leaflet supplied in each pack of medicine.

Clozapine was first authorised in 1989 and is now indicated for treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics. Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for adequate duration.

Clozapine is also authorised to treat psychotic disorders occurring in patients with Parkinson's disease, in cases where standard treatment has failed. Clozapine is associated with several potentially serious side effects which are outlined in the product information, that require monitoring of various aspects of patient’s health to minimise risks including monitoring: white blood cells, blood pressure, heart function, liver function, body weight, glucose, cholesterol, other medication, falls and for signs of infection.

As clozapine is used when other treatments have failed to manage a patient’s condition, careful monitoring is required to minimise the risks to ensure patients are able to receive effective treatment with clozapine.

The safety of clozapine is continuously monitored by the MHRA to ensure the product information reflects what is known about the medicine. The MHRA is in the process of reviewing the blood monitoring requirements and will be seeking views in the summer from patients, patients’ families and healthcare professionals on methods to improve awareness of the risks associated with clozapine and how to manage them.

Clozapine is licenced by the Medicines and Healthcare products Regulatory Agency (MHRA). Products are licenced by the MHRA where the benefit-risk assessment has been found to be positive in relation to quality, safety, and efficacy. Clozapine is marketed in different strengths and formulations, for the following indications.

Firstly, Clozapine is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics. Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for an adequate duration. Secondly, Clozapine is indicated in psychotic disorders occurring during the course of Parkinson's disease, in cases where standard treatment has failed. Further information is available on the MHRA’s website, which is available at the following link:

https://products.mhra.gov.uk/

The Department is not aware of any supply issues regarding the provision of this medicine. Furthermore, decisions about what medicines to prescribe are made by the doctor or healthcare professional responsible for that part of the patient’s care. Prescribers are accountable for their prescribing decisions.

It is for the responsible clinician to work with their patient and decide on the best course of treatment, with the provision of the most clinically appropriate care for the patient always being the primary consideration. Prescribers must always satisfy themselves that the medicines they consider appropriate for their patients can be safely prescribed and that they take account of appropriate national guidance on clinical effectiveness, as well as the local commissioning decisions of their respective integrated care boards (ICBs). The National Institute for Health and Care Excellence (NICE) has developed a Quality Standard on psychosis and schizophrenia in adults. NICE quality standards are concise sets of statements designed to drive quality improvements within a particular area of care and cover the NHS, public health, and social care. The Quality Standard recommends that adults with schizophrenia that have not responded adequately to treatment with at least two antipsychotic drugs are offered Clozapine, and provides quality measures to be used by service providers, commissioners, and healthcare professionals to assess the quality of care or service provision.

No specific guidance has been issued.

The product information for clozapine for healthcare professionals and patients advises against drinking alcohol during treatment with that drug. The Medicines and Healthcare products Regulatory Agency provided a Drug Safety Update which recommends that blood concentration of clozapine should be monitored for toxicity in clinical situations, such as during smoking cessation or if a patient transfers to e-cigarettes. The British National Formulary advises that dose adjustment may be necessary if a patient’s smoking habits change during treatment with clozapine.