UK Parliament
The Medicines and Healthcare products Regulatory Agency (MHRA) is reviewing blood monitoring requirements for patients using clozapine and will seek views on how to improve awareness and management of the risks associated with the antipsychotic medicine, a health minister has said.
In answer to a parliamentary question, asking what assessment has been made of the side effects and long-term health implications of the drug, health minister Karin Smyth acknowledged that “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”.
Smyth continued that the safety of clozapine is “continuously monitored by the MHRA to ensure the product information reflects what is known about the medicine”, adding that “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 indicated for patients with treatment-resistant schizophrenia and patients with schizophrenia 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.
However, clozapine is associated with several potentially serious side effects, such as agranulocytosis and tachycardia, which require regular monitoring to minimise risks, including monitoring of white blood cells, blood pressure, heart function, liver function, body weight, glucose, cholesterol, other medication, falls and signs of infection.
In 2020, the MHRA issued a drug safety alert, advising that monitoring blood concentrations of clozapine for toxicity was “advised in certain clinical situations”, such as when a patient stops smoking or poor clozapine metabolism is suspected.
The alert also stated that if clozapine-level monitoring in the blood is carried out, it should be “in addition to the required blood tests to manage the risk of agranulocytosis”.
However, questions about the monitoring of clozapine patients were raised in 2023 by Louise Hunt, senior coroner for Birmingham and Solihull, following the death of a man with treatment-resistant schizophrenia in 2022 who had been taking clozapine.
Although concluding that the cause of death was “natural causes”, Hunt wrote to the MHRA to express concern that systems were not in place to monitor abnormal levels of clozapine.
In a statement to The Pharmaceutical Journal on the MHRA’s review, the College of Mental Health Pharmacy said it welcomed the review and hoped “that our membership of expert mental health pharmacists will be offered an opportunity to contribute to discussions about best practice standards that may come out of this review”.
“We know that clozapine is the only recommended drug for treatment-resistant schizophrenia, and yet, the need for regular blood tests is a significant barrier to its use. The current system uses up extensive secondary care resource and is arguably preventing psychiatric services from focusing on a wider range of potential side effects. It also introduces the risk that GPs may not be aware of patients who are taking clozapine because most do not prescribe it,” it said.
However, it added: “Blood dyscrasias are not the major side effect of concern for those taking the drug in the longer term. A holistic approach to physical health monitoring is required, and this should be done in close collaboration with primary care, where interventions addressing metabolic disease, constipation and smoking cessation can also be made.”
