Clozapine treatment during Covid-19 outbreak

Covid-19 may result in patients self-isolating and being unable to attend for their full blood counts or being reluctant to travel to clinics for sampling. Similarly there may be staffing issues that mean it becomes very difficult to maintain normal clinic approaches. In both instances a pragmatic approach is required that supports patient safety with regards to clozapine monitoring but also reflects the realities of the Covid-19 outbreak.

• Patients with a fever: IMMEDIATELY test for both agranulocytosis and Covid-19 especially if they are also showing others signs of these conditions e.g. coughing, sore throat, shortness of breath and a runny nose
• For patients self-isolating: use the maximum validity possible between blood samples i.e.
  • Weekly patients 14 days. Mylan apply a 10 day validity to samples but we have 10 years experience of applying 14 days so the increased risk is acceptable. Note treatment from day 10 – 14 with Clozaril would be unlicensed
  • Fortnightly patients 21 days
  • 4 weekly patients 42 days.

Given the current isolation advice this should support on-going dispensing in most instances.

• For patients who can’t or won’t travel to their usual blood sampling location:
  • Strongly urge patients to attend as normal
  • Use the maximum validity possible between blood samples
  • Consider undertaking blood sampling in patients’ homes.
• Services unable to undertake normal blood sampling processes:
  • If it proves impossible for services to undertake normal blood sampling processes consider dispensing off license without blood testing. This will require support from CPMS, DMS & ZTAS and board level governance approval.
• Please record any actions taken on EMIS and inform pharmacy of any delays in blood testing.

Clozapine supplies to patients must be maintained to prevent unnecessary treatment breaks and potential relapse. The following actions are recommended

• Dispense to the maximum blood validity where necessary: most patients should continue to receive their normal supplies however it may necessary and appropriate to dispense to the full blood count validity to support self-isolation or blood sampling difficulties
• Continue to dispense without a valid blood: depending on individual circumstances or service issues it may be necessary to routinely dispense prescriptions without any valid bloods being available. This should be a last resort and would be unlicensed. This will require support from CPMS, DMS & ZTAS and board level governance approval
• Prescription collection: normal prescription collection or delivery processes may be disrupted. Patients should be advised to contact their local mental health services or pharmacy for advice if they are unable to collect their medicines themselves.

Patients will be understandably anxious at this time providing appropriate reassurance may be necessary.

Patients should be advised to follow national guidance about self-isolation and other measures but also to contact mental health services for advice about blood testing.

There is no clear data that suggests that clozapine patients should not continue to take their clozapine if they are confirmed or suspected to have contracted COVID-19. However bacterial or viral infections have been reported to increase clozapine plasma levels by inhibiting metabolism.

The following approach is advised for patients with a confirmed diagnosis of Covid-19:

• For patients with mild symptoms maintain the current dose, take a trough plasma level if possible and monitor closely for signs of clozapine toxicity (CNS depression, tachycardia, seizures and hypersalivation)
• For patients with moderate to severe symptoms or displaying signs of clozapine toxicity half the clozapine dose until the symptoms resolve - this is particularly important in patients who are hospitalised and forced to stop smoking, smoking cessation can cause a further rise in plasma levels of up to 50%.
• If the patient has a fragile mental state with high risk of psychotic relapse, 25% reduction may be appropriate, but this is a clinical decision; always keep monitoring for signs of clozapine toxicity and reduce dose further if these emerge.

Twice weekly blood tests for amber results should be attempted but may be impractical and therefore consideration should be given to maintaining standard routine blood tests for amber results. Consideration of individual patient circumstances i.e. previous blood results history will be necessary.

Daily blood tests following a red result may also be impractical for community based patients. Consideration should be given to admitting all red alert patients to hospital to support the necessary blood testing.

Routine clozapine plasma levels should be temporarily suspended.

Undertaking additional plasma levels may be impractical and therefore clinical management of patients with pragmatic dose reductions is recommended.

Consideration should be given on a case by case basis to the benefits and risks of new starts and especially red re-challenges. Patients may be unwilling to come into hospital to start treatment and there may be a pressure to use beds for higher priorities.

Given the uncertain effects of Covid-19 on white blood cells it may be prudent to avoid exposing previously neutropenic patients to clozapine at this time.