This page provides advice on the monitoring and prescribing of clozapine during the COVID-19 pandemic

Although many hospital and out of hospital services have begun to resume following a period of lockdown, some patients may still require an extension to their clozapine monitoring schedules. The advice below provides recommendations to maintain the safe management of clozapine when monitoring is affected by the COVID-19 pandemic.

General guidance for medicines management of mental health patients during COVID-19 is available from the Royal College of Psychiatrists

This page gives advice on drug monitoring during COVID-19 for clozapine.

Usual care and monitoring can be summarised as: 

  • An important part of clozapine safety is maintenance of good physical health and awareness of clozapine-related adverse drug events (such as constipation or fever); patients must report potentially serious ADEs urgently to a clinician
  • Establish leucocyte and neutrophil levels via one of the central clozapine monitoring systems before making any new supply
  • A patient’s individual risk of clozapine-induced neutropenia and agranulocytosis determines the frequency of testing; testing intervals are every week, every 2 weeks, or every 4 weeks
  • Flexibility exists in testing intervals and quantities that can be dispensed to patients for individual clozapine brands as shown in the tables below

Table 1: Shows maximum clozapine cover period for Clozaril® and Denzapine®

Monitoring Frequency Sample Due Day Maximum Cover Period
Weekly Every 7 Days 10 Days (additional 3 days supply)
Fortnightly Every 14 Days 21 Days (additional 7 days supply)
Four Weekly Every 28 Days 42 Days (additional 14 days supply)

Table 2: Shows maximum clozapine cover period for Zaponex®

Monitoring Frequency Sample Due Day Maximum Cover Period
Weekly Every 7 Days 14 Days (additional 7 days supply)
Fortnightly Every 14 Days 21 Days (additional 7 days supply)
Four Weekly Every 28 Days 42 Days (additional 14 days supply)

During the COVID-19 pandemic, recommendations are:

  • Normal monitoring of WCC for clozapine-treated patients may be unavoidably disrupted during the pandemic
  • Where possible, follow the licensed dispensing and testing interval extensions tabulated above
  • Where further extensions are required, these may fall outside the licence. Patients should be risk stratified and monitored as below:
    1. Patients in the first 18 weeks of clozapine use are at the highest risk of neutropenia and agranulocytosis and should continue weekly monitoring within limits tabulated above
    2. Patients in weeks 19 to 52 without a history of low white cell count related to clozapine should be reviewed on an individual basis. Some extension beyond manufactures’ limits may be appropriate. Seek advice from the relevant clozapine manufacturer as well as local medical and ethical bodies (which should already exist).
    3. Patients with more than 1 year of use and without a history of low white cell count related to clozapine: consider temporary extension of blood tests from every 4 weeks to up to every 12 weeks.
  • Where any extension to clozapine blood testing is made, the relevant manufacturer must be made aware; they will note that clozapine is dispensed off licence and may require off licence forms to be completed
  • Further advice on the management of clozapine during COVID-19 is available from each manufacturer of clozapine: Clozaril®Zaponex®, and Denzapine®
  • South London and Maudsley Hospital have also produced guidance for use during the COVID-19 pandemic.

For patients with COVID-19 symptoms, recommendations are: 

  • Continue clozapine but take a blood sample immediately to determine WCC; absolute neutrophil count (ANC); and clozapine plasma concentration
  • If the patient is suspected of having a serious clozapine-related ADE then stop clozapine and investigate appropriately
  • Symptoms of COVID-19 can mimic clozapine related ADEs: notably, myocarditis and neutropenic sepsis; specific considerations include:
    • Myocarditis: clozapine related myocarditis is more likely to occur within the first 6 weeks of treatment.  Therefore after the initial period, the likelihood of any myocarditis being clozapine related reduces.
    • White cell count: COVID-19 can cause a reduction in lymphocytes and therefore total white cell count. In some patients taking clozapine, it may also cause a mild and transient reduction in neutrophils. This reduction in neutrophils is small (mean around 1 x 109/L) and recovers quickly (within 2 weeks). Clinicians should act to rule out COVID-19 infection in patients presenting with a fall in neutrophil counts. Clozapine can usually be continued in patients who are COVID-19 positive, have been taking clozapine for more than 6 months, have not had neutropaenia previously, and where the neutrophil count stays above 1.0 x 109/L.. See further advice: Covid-19 and Clozapine – SLAM Guidance

Acknowledgements

This page was developed in conjunction with Dr Siobhan Gee, Principal Pharmacist at the Maudsley Hospital, Professor David Taylor, Director of Pharmacy at the Maudsley Hospital; and Peter Pratt, Specialist Mental Health Pharmacy Advisor at NHSEI. We are hugely grateful for their input.

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Change history

  1. Information about impact of COVID-19 on neutrophil count updated in line with specialist opinion and emerging published evidence.
  1. Summary added and additional context provided for the recommendations of increasing monitoring intervals. Formatting
  1. Published