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: A supply will be issued to cover self-isolation period and to allow time for a blood sample to be taken and will be agreed on an individual patient basis.

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

• 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.

The Department of Health and Social Care have identified patient cohorts who are at the highest risk from covid-19 and who are prioritised for neutralising monoclonal antibody or antiviral treatment in the community (a list can be found here). Patients in the community on clozapine may fall within these categories. The antiviral, Paxlovid (nirmatrelvir/ritonavir), is contraindicated in combination with clozapine due to the potential to increase clozapine plasma levels. As clozapine is a hospital only medication it does not always appear on GP patient records and Paxlovid may inadvertently be prescribed in this group. If a patient inadvertently receives treatment with Paxlovid they should be assess urgently for signs of clozapine toxicity and pharmacy contacted for advice.

MH Pharmacy should be contacted to determine the appropriate treatment for those prescribed clozapine.

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.