Clozapine drug monitoring during COVID-19 for stable adult patients

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

Advice on other medicines with drug monitoring schedules during this time is here

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 WCC but does not appear to affect neutrophil levels, whilst clozapine does.  Therefore if neutrophil levels are stable, continue clozapine. See further advice: Clozapine and blood dyscrasias in patients with coronavirus (COVID-19)

This page was developed in conjunction with 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.