Clozapine drug monitoring during COVID-19 for stable adult patients

Sheena Vithlani, Regional Medicines Information Manager, London Medicines Information ServicePublished Last updated See all updates

During COVID-19, extended monitoring intervals may be possible for some patients, and particular actions are necessary for patients with COVID-19 symptoms.

Although many hospital and out of hospital services are operating normally, 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.

Normal practice

A number of actions maintain clozapine safety in normal practice

Physical health

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.

Blood monitoring

You should:

  • Establish leucocyte and neutrophil levels via one of the central clozapine monitoring systems before making any new supply
  • Determine a patient’s frequency of testing through their individual risk of clozapine-induced neutropenia and agranulocytosis; testing intervals are every week, every 2 weeks, or every 4 weeks

Testing intervals

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)

Recommendations during COVID-19 pandemic

Maintain normal monitoring wherever possible

Wherever possible, follow the licensed dispensing and testing interval extensions; however, normal monitoring of WCC for clozapine-treated patients may be unavoidably disrupted during the pandemic.

Risk stratify patients

Where further extensions are required, these may fall outside the licence. Patients should be risk stratified and monitored as below:

Patients in first 18 weeks

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 above.

Patients in weeks 19 to 52

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).

Patients after 1 year

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.

Inform manufacturer

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®

Patients with COVID-19 symptoms

For patients with COVID-19 symptoms, recommendations are as follows.

No symptoms of Clozapine adverse event

For these patients, continue clozapine but take a blood sample immediately to determine:

  • WCC
  • absolute neutrophil count (ANC)
  • clozapine plasma concentration

Symptoms of Clozapine adverse event

If the patient is suspected of having a serious clozapine-related ADE then stop clozapine and investigate appropriately.

Apply caution in symptom attribution

Symptoms of COVID-19 can mimic clozapine related ADEs, notably myocarditis and neutropenic sepsis. Consider that:

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.

Further guidance

Clozapine

South London and Maudsley Hospital has also produced guidance for use during the COVID-19 pandemic.

Other mental health guidance

For general guidance on the management of medicines to treat mental health conditions during COVID-19 use the Royal College of Psychiatrists advice.

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
  • Peter Pratt, Specialist Mental Health Pharmacy Advisor at NHSEI

We are hugely grateful for their input.

Change history

  1. Page re-done to add headings and improve clarity of messages.
  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
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