An international guideline with six personalised titration schedules for preventing myocarditis and pneumonia associated with clozapine

Jose De Leon, Can Jun Ruan, Georgios Schoretsanitis, Christopher Rohde, Elif Anll Yaǧcloǧlu, Trino Baptista, Oleg O. Kirilochev, Carlos De Las Cuevas, Christoph U. Correll

Research output: Contribution to journalComment/debate

20 Scopus citations

Abstract

White blood cell (WBC) monitoring has reduced clozapine-treated patient deaths associated with agranulocytosis to a rarity. However, clozapine protocols and package inserts worldwide provide no instructions for preventing myocarditis or pneumonia during clozapine titrations. Prescribers worldwide are largely unaware of that. Meanwhile, as they worry about agranulocytosis, their clozapine-treated patients are at risk of dying from pneumonia or myocarditis. Consequently, an international guideline with 104 authors from 50 countries/regions was recently published to provide personalised clozapine titration schedules for adult inpatients. This forum article reviews pneumonia and myocarditis occurring during clozapine titration, as well as the three most innovative aspects of this new guideline: (1) personalised titration, (2) C reactive protein (CRP) measures, and (3) dose predictions based on blood levels. Clozapine metabolism is influenced by 3 levels of complexity: (1) ancestry groups, (2) sex-smoking subgroups, and (3) presence/absence of poor metabolizer status. These 3 groups of variables should determine the maintenance dose and speed of clozapine titration; they are summarised in a table in the full-text. The international clozapine titration guideline recommends measuring CRP levels simultaneously with WBC, at baseline and weekly at least for the first 4 weeks of titration, the highest risk period for clozapine-induced myocarditis.

Original languageEnglish
Article numbere100773
JournalGeneral Psychiatry
Volume35
Issue number3
DOIs
StatePublished - Jun 1 2022

Bibliographical note

Publisher Copyright:
© 2022 BMJ Publishing Group. All rights reserved.

Funding

In the last 3 years, GS has served as a consultant for HLS Therapeutics; EAY has received speaker’s honoraria and consulting fees from Janssen and Abdi İbrahim Otsuka and CUC has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Cardio Diagnostics, Compass, Damitsa, Gedeon Richter, Hikma, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mindpax, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Relmada, Reviva, Rovi, Seqirus, Servier, SK Life Science, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva and Viatris. He provided expert testimony for Janssen and Otsuka. He served on Data Safety Monitoring Boards for Lundbeck, Relmada, Reviva, Rovi, Supernus and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, LB Pharma and Mindpax. In the last 3 years, JdL, C-JR, CR, TB, OOK and CDlC report no conflicts of interest.

FundersFunder number
Janssen and Takeda

    Keywords

    • schizophrenia

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Psychiatry and Mental health

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