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An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels
J. de Leon, G. Schoretsanitis, RL. Smith, E. Molden, A. Solismaa, N. Seppälä, M. Kopeček, P. Švancer, I. Olmos, C. Ricciardi, C. Iglesias-Garcia, A. Iglesias-Alonso, E. Spina, CJ. Ruan, CY. Wang, G. Wang, YL. Tang, SK. Lin, HY. Lane, YS. Kim, SH....
Language English Country Germany
Document type Journal Article
PubMed
34911124
DOI
10.1055/a-1625-6388
Knihovny.cz E-resources
- MeSH
- Antipsychotic Agents * adverse effects MeSH
- Asian People MeSH
- C-Reactive Protein MeSH
- Adult MeSH
- Clozapine * adverse effects MeSH
- Valproic Acid adverse effects MeSH
- Humans MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
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.
Addictions Division Centre for Addiction and Mental Health Toronto Canada
Casa de Salidedo Som Jesus Oporto Portugal
Center for Psychopharmacology Diakonhjemmet Hospital Oslo Norway
Charité Universitätsmedizin Berlin Department of Child and Adolescent Psychiatry Berlin Germany
College of Pharmacy QU Health Qatar University Doha Qatar
Department and Institute of Psychiatry and Mental Health Oporto Faculty of Medicine Oporto Portugal
Department and Institute of Psychiatry University of São Paulo Medical School Sao Paulo Brazil
Department for Psychiatry and Psychological Medicine University Hospital Center Zagreb Croatia
Department of Affective Disorders Aarhus University Hospital Psychiatry Aarhus Denmark
Department of Clinical and Experimental Medicine University of Messina Messina Italy
Department of Clinical Medicine Aarhus University Aarhus Denmark
Department of Clinical Pharmacology Astrakhan State Medical University Astrakhan Russian Federation
Department of Neuropsychiatry Keio University School of Medicine Tokyo Japan
Department of Pharmacy Hôpital du Sacré Cœur de Montréal Montreal Canada
Department of Pharmacy Mayo Clinic Rochester MN USA
Department of Pharmacy Practice University of Montana Missoula USA
Department of Physiology Los Andes University Medical School Mérida Venezuela
Department of Psychiatry and Psychotherapy University Medical Center of Mainz Germany
Department of Psychiatry Asahi General Hospital Chiba Japan
Department of Psychiatry Autonomous University of Barcelona Spain
Department of Psychiatry Beijing Anding Hospital Capital Medical University Beijing China
Department of Psychiatry Charles University 3rd Faculty of Medicine Prague Czech Republic
Department of Psychiatry Christian Medical College Vellore India
Department of Psychiatry Hacettepe University Faculty of Medicine Ankara Turkey
Department of Psychiatry Hamad Medical Corporation Doha Qatar
Department of Psychiatry Linkou Chang Gung Memorial Hospital Taoyuan Taiwan
Department of Psychiatry LSK Faculty of Medicine The University of Hong Kong Hong Kong SAR
Department of Psychiatry Massachusetts General Hospital Harvard Medical School Boston MA USA
Department of Psychiatry Medical University of Gdańsk Gdańsk Poland
Department of Psychiatry Okayama Psychiatric Medical Center Okayama Japan
Department of Psychiatry Post Graduate Institute of Medical Education and Research Chandigarh India
Department of Psychiatry Queens University Kingston Canada
Department of Psychiatry Satasairaala Finland
Department of Psychiatry School of Medicine Pontificia Universidad Católica de Chile Santiago Chile
Department of Psychiatry School of Medicine Taipei Medical University Taipei Taiwan
Department of Psychiatry School of Medicine University Hospital Virgen del Rocio IBIS Sevilla Spain
Department of Psychiatry School of Medicine University of Zagreb Zagreb Croatia
Department of Psychiatry Tampere University Hospital Tampere Finland
Department of Psychiatry The University of Melbourne Melbourne Victoria Australia
Department of Psychiatry University Medical Centre Maribor Maribor Slovenia
Department of Psychiatry University of Kentucky Lexington KY USA
Department of Psychiatry University of Toronto Toronto Ontario Canada
Department of Psychiatry Washington University in St Louis St Louis Missouri USA
Department of Psychological Medicine University of Otago Wellington New Zealand
Department of Psychology College of Medical and Health Sciences Asia University Taichung Taiwan
Dutch Clozapine Collaboration Group Castricum The Netherlands
East London NHS Foundation Trust London United Kingdom
Eastern State Hospital Lexington Kentucky USA
Faculdade de Medicina da Universidade do Porto Porto Portugal
Facultad de Química Universidad Nacional Autónoma de México México City México
Faculty of Medicine and Health Technology Tampere University Tampere Finland
Faculty of Medicine University of Montreal Montreal Canada
Faculty of Medicine University of Sfax Sfax Tunisia
Federal Neuropsychiatric Hospital Yaba Lagos Nigeria
Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan
Group of Resistant Schizophrenia Federal University of Sao Paulo SP Brazil
Hazelwood Center Louisville Kentucky USA
Hospital Central de Maputo Maputo Mozambique
Hospital Universitario Central de Asturias Oviedo Spain
Hospital Universitario de Canarias Tenerife Spain
Hospital Valle del Nalón Langreo Spain
Institute of Neuropsychiatry and Addictions Parc de Salut Mar Barcelona Spain
Instituto Nacional de Neurología y Neurocirugía México City México
Instituto Vilapriño Center for Studies Assistance and Research in Neurosciences Mendoza Argentina
Mental Health Centre Glostrup Copenhagen University Hospital Copenhagen Denmark
Mental Health Research Center Eastern State Hospital Lexington KY USA
Mental Health Team Alkmaar Mental Health Services Noord Holland Noord Alkmaar The Netherlands
Metro South Addiction and Mental Health Service Brisbane Australia
National Institute of Mental Health Klecany Czech Republic
National Institute of Mental Health Neurology and Neurosurgery Budapest Hungary
New York Medical College Department of Psychiatry and Behavioral Sciences Valhalla NY USA
NHS Department of Mental Health G Mazzini Hospital Teramo Italy
Programa Trastornos del Ánimo Hospital Universitario San Vicente Fundación Medellín Colombia
Psychiatry A Department Hedi Chaker University Hospital Sfax Tunisia
Psychiatry Department Centro Hospitalar Universitário de S João Porto Portugal
School of Medicine Virginia Commonwealth University Richmond VA USA
School of Pharmaceutical Sciences University of Geneva Switzerland
Semel Institute for Neuroscience at UCLA Los Angeles CA USA
Sigmund Freud University Vienna Austria
Spanish Network for Research in Mental Health Instituto de Salud Carlos 3 Madrid Spain
Spanish Network for Research in Mental Health Sevilla Spain
State Key Laboratory of Brain and Cognitive Sciences The University of Hong Kong Hong Kong SAR
Substance Abuse Treatment Program Atlanta VA Medical Center Decatur Georgia USA
The Zucker Hillside Hospital Psychiatry Research Northwell Health Glen Oaks New York USA
Universidad de Oviedo CIBERSAM INEUROPA ISPA FIMBA Oviedo Spain
University of Kragujevac Faculty of Medical Sciences Department of Psychiatry Kragujevac Serbia
VA Desert Pacific Mental Illness Research Education and Clinical Center Los Angeles CA USA
References provided by Crossref.org
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