Jose de Leon
An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels
de Leon, Jose; Schoretsanitis, Georgios; Smith, Robert L.; Molden, Espen; Solismaa, Anssi; Seppälä, Niko; Kopeček, Miloslav; Švancer, Patrik; Olmos, Ismael; Ricciardi, Carina; Iglesias-Garcia, Celso; Iglesias-Alonso, Ana; Spina, Edoardo; Ruan, Can-Jun; Wang, Chuan-Yue; Wang, Gang; Tang, Yi-Lang; Lin, Shih-Ku; Lane, Hsien-Yuan; Kim, Yong Sik; Kim, Se Hyun; Rajkumar, Anto P.; González-Esquivel, Dinora F.; Jung-Cook, Helgi; Baptista, Trino; Rohde, Christopher; Nielsen, Jimmi; Verdoux, Hélène; Quiles, Clelia; Sanz, Emilio J.; De Las Cuevas, Carlos; Cohen, Dan; Schulte, Peter F.J.; Ertuğrul, Aygün; Anıl Yağcıoğlu, A. Elif; Chopra, Nitin; McCollum, Betsy; Shelton, Charles; Cotes, Robert O.; Kaithi, Arun R.; Kane, John M.; Farooq, Saeed; Ng, Chee H.; Bilbily, John; Hiemke, Christoph; López-Jaramillo, Carlos; McGrane, Ian; Lana, Fernando; Eap, Chin B.; Arrojo-Romero, Manuel; Rădulescu, Flavian Ş.; Seifritz, Erich; Every-Palmer, Susanna; Bousman, Chad A.; Bebawi, Emmanuel; Bhattacharya, Rahul;...
Authors
Georgios Schoretsanitis
Robert L. Smith
Espen Molden
Anssi Solismaa
Niko Seppälä
Miloslav Kopeček
Patrik Švancer
Ismael Olmos
Carina Ricciardi
Celso Iglesias-Garcia
Ana Iglesias-Alonso
Edoardo Spina
Can-Jun Ruan
Chuan-Yue Wang
Gang Wang
Yi-Lang Tang
Shih-Ku Lin
Hsien-Yuan Lane
Yong Sik Kim
Se Hyun Kim
Anto P. Rajkumar
Dinora F. González-Esquivel
Helgi Jung-Cook
Trino Baptista
Christopher Rohde
Jimmi Nielsen
Hélène Verdoux
Clelia Quiles
Emilio J. Sanz
Carlos De Las Cuevas
Dan Cohen
Peter F.J. Schulte
Aygün Ertuğrul
A. Elif Anıl Yağcıoğlu
Nitin Chopra
Betsy McCollum
Charles Shelton
Robert O. Cotes
Arun R. Kaithi
John M. Kane
Saeed Farooq s.farooq@keele.ac.uk
Chee H. Ng
John Bilbily
Christoph Hiemke
Carlos López-Jaramillo
Ian McGrane
Fernando Lana
Chin B. Eap
Manuel Arrojo-Romero
Flavian Ş. Rădulescu
Erich Seifritz
Susanna Every-Palmer
Chad A. Bousman
Emmanuel Bebawi
Rahul Bhattacharya
Deanna L. Kelly
Yuji Otsuka
Judit Lazary
Rafael Torres
Agustin Yecora
Mariano Motuca
Sherry K.W. Chan
Monica Zolezzi
Sami Ouanes
Domenico De Berardis
Sandeep Grover
Ric M. Procyshyn
Richard A. Adebayo
Oleg O. Kirilochev
Andrey Soloviev
Konstantinos N. Fountoulakis
Alina Wilkowska
Wiesław J. Cubała
Muhammad Ayub
Alzira Silva
Raphael M. Bonelli
José M. Villagrán-Moreno
Benedicto Crespo-Facorro
Henk Temmingh
Eric Decloedt
Maria R. Pedro
Hiroyoshi Takeuchi
Masaru Tsukahara
Gerhard Gründer
Marina Sagud
Andreja Celofiga
Dragana Ignjatovic Ristic
Bruno B. Ortiz
Helio Elkis
António J. Pacheco Palha
Adrián LLerena
Emilio Fernandez-Egea
Dan Siskind
Abraham Weizman
Rim Masmoudi
Shamin Mohd Saffian
Jonathan G. Leung
Peter F. Buckley
Stephen R. Marder
Abstract
This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600?ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350?ng/mL. In the US, daily doses of 300-600?mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150?mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300?mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200?mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400?mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300?mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600?mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
Citation
de Leon, J., Schoretsanitis, G., Smith, R. L., Molden, E., Solismaa, A., Seppälä, N., …Marder, S. R. (2021). An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels. Pharmacopsychiatry, 55(02), 73-86. https://doi.org/10.1055/a-1625-6388
Journal Article Type | Review |
---|---|
Acceptance Date | Aug 23, 2021 |
Online Publication Date | Dec 15, 2021 |
Publication Date | Dec 15, 2021 |
Journal | Pharmacopsychiatry |
Print ISSN | 0176-3679 |
Publisher | Thieme Gruppe |
Volume | 55 |
Issue | 02 |
Pages | 73-86 |
DOI | https://doi.org/10.1055/a-1625-6388 |
Keywords | Pharmacology (medical), Psychiatry and Mental health, General Medicine |
Public URL | https://keele-repository.worktribe.com/output/421939 |
Publisher URL | https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1625-6388 |
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