There are over 3,500 patients in Scotland prescribed the second generation antipsychotic; clozapine. Continuing an unbroken supply of clozapine is essential to maintaining their mental health and well being and preventing relapse. Clozapine supplies are linked to mandatory full blood count monitoring at weekly, fortnightly or 4 weekly intervals. The COVID-19 outbreak presents a unique challenge to the continuous and safe maintenance of clozapine treatment. This document provides a potential approach to the management of clozapine patients during this national emergency.
Main issues to consider:
- Managing patients who are symptomatic
- Maintaining routine full blood counts (FBC)
- Maintaining prescription supplies
- Providing appropriate patient advice
- Dose management
1. Managing patients who are symptomatic
Where a patient has symptoms that may be suggestive of COVID-19 eg fever, cough, flu-like symptoms, which may also be indicative of neutropenia, this should be discussed with the patient’s psychiatrist as a matter of urgency and an urgent FBC should be taken to rule out potential clozapine-induced neutropenia. Any red or amber result should be acted upon accordingly. FBCs from patients with suspected COVID-19 symptoms should be done within the patient’s home. Standard personal protective equipment (PPE) advice should be followed and samples handled according to local laboratory specimen sampling advice. The patient should not be asked to attend high risk areas such as the local hospital for bloods.
2. Maintaining routine full blood counts
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.
- For patients self-isolating without symptoms: 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 to 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.
Note: flu-like symptoms and a high temperature may suggest neutropenia so it is important to undertake a full blood count as soon as possible.
- 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 following current PPE advice.
- 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 approval from a consultant psychiatrist on a case-by-case basis.
3. Maintaining clozapine supplies
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 be 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 dispense prescriptions without any valid bloods being available. This should be a last resort and would be unlicensed. This will require approval from a consultant psychiatrist on a case-by-case basis. Any supplies of clozapine in excess of sample validity should be for the shortest period possible and bloods should be obtained as soon as practically possible.
Where a patient is subject to compulsory treatment under the Mental Health (Care and Treatment Scotland) Act 2004, off-licence use of clozapine would be in breach of the specification of the T3 and the patient’s RMO will need to seek DMP approval for a change in the treatment plan.
- Prescription collection: normal prescription collection or delivery processes may be disrupted. Patients should be advised to contact their local Community Mental Health Team or New Craigs pharmacy for advice if they are unable to collect their medicines themselves.
4. Providing appropriate patient advice
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 New Craigs pharmacy for advice about blood testing.
5. Dose management
There is no clear evidence regarding the impact of COVID-19 on clozapine plasma levels. A pragmatic approach is advised.
- For patients with mild respiratory symptoms, maintain the current dose and consider taking a trough clozapine plasma level (10 to 14 hours post dose). Respiratory infections can cause an increase in clozapine plasma levels with associated increased side effects. A temporary decrease in clozapine dose may be required.
- For patients with severe respiratory symptoms suspend clozapine treatment until the symptoms resolve. If clozapine has been withheld for more than 48 hours, restarting clozapine requires gradual re-titration. Contact the patient’s consultant psychiatrist or specialist pharmacist for advice.
- For smokers who are unable to continue smoking due to illness consider a dose reduction.
Other issues to consider
Amber & red alert protocols
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.
Clozapine new starts and red re-challenges
Consideration should be given on a case by case basis to the benefits and risks of new starts and especially red re-challenges. 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.