Clozapine,mRNA COVID-19 vaccination and drug-induced myocarditis

Clozapine-induced myocarditis (CIM) has been reported to occur in over 8% of initiations in some Australian centres (Dawson et al., 2018). The Australian Technical Advisory Group on Immunisation (ATAGI) and Cardiac Society of Australia and New Zealand (CSANZ) recognise the rare risk of myocarditis or pericarditis after mRNA COVID-19 vaccination but advise in general the benefits of vaccination far outweigh the risks.

We encountered two situations in which patients were hospitalised for clozapine initiation on dates that coincided with scheduled mRNA COVID-19 vaccination. In the first situation, the second COVID-19 vaccination was due and clozapine initiation was delayed by 14 days. In the second situation, the first COVID-19 vaccination was booked for week 3 post clozapine initiation, so it was rescheduled until after the 4-week risk period for CIM. This second patient developed CIM shortly after week 3 post commencement and did not have their mRNA COVID-19 vaccination.

CIM typically presents within 14–28 days of commencement (Ronaldson et al., 2011). During the initial 4 weeks of treatment, patients are advised to monitor for signs and symptoms of myocarditis, as well as weekly monitoring of CRP and troponin. This monitoring practice is suggested to account for the higher reported incidence in Australia (Dawson et al., 2018). In the context of myocarditis post mRNA COVID-19 vaccination, the risk of myocarditis may be greatest in young males under 30 years and appears to be higher following the second dose of an mRNA COVID-19 vaccination. Symptoms typically emerge within 14 days of vaccination, most reported within 1–5 days (ATAGI and CSANZ, 2021).

Our health service decided to initiate clozapine and administer mRNA vaccination at different times to avoid an overlap in risk periods which may result in an unnecessary contraindication of either agent. Our decision as to which should take precedence, clozapine or the vaccination, was based on factors including patient preference, the presence of local community transmission of COVID-19, the mental state of the consumer, whether clozapine initiation could be deferred, and the capacity of the patient to consent to the vaccination. Based on our experience, advice in relation to clozapine initiation and mRNA vaccination was subsequently issued by the SA Health Clozapine Strategic Management Group. An alternative approach would have been to administer a vector COVID-19 vaccination such as Vaxzevria (AstraZeneca) that does not appear to cause myocarditis (ATAGI and CSANZ, 2021).