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AuthorDe Leon, Jose
AuthorSchoretsanitis, Georgios
AuthorSmith, Robert L.
AuthorMolden, Espen
AuthorSolismaa, Anssi
AuthorSeppälä, Niko
AuthorKopeček, Miloslav
AuthorŠvancer, Patrik
AuthorOlmos, Ismael
AuthorRicciardi, Carina
AuthorIglesias-Garcia, Celso
AuthorIglesias-Alonso, Ana
AuthorSpina, Edoardo
AuthorRuan, Can Jun
AuthorWang, Chuan Yue
AuthorWang, Gang
AuthorTang, Yi Lang
AuthorLin, Shih Ku
AuthorLane, Hsien Yuan
AuthorKim, Yong Sik
AuthorKim, Se Hyun
AuthorRajkumar, Anto P.
AuthorGonzález-Esquivel, Dinora F.
AuthorJung-Cook, Helgi
AuthorBaptista, Trino
AuthorRohde, Christopher
AuthorNielsen, Jimmi
AuthorVerdoux, Hélène
AuthorQuiles, Clelia
AuthorSanz, Emilio J.
AuthorDe Las Cuevas, Carlos
AuthorCohen, Dan
AuthorSchulte, Peter F.J.
AuthorErtuǧrul, Aygün
AuthorAnll Yaǧcloǧlu, A. Elif
AuthorChopra, Nitin
AuthorMcCollum, Betsy
AuthorShelton, Charles
AuthorCotes, Robert O.
AuthorKaithi, Arun R.
AuthorKane, John M.
AuthorFarooq, Saeed
AuthorNg, Chee H.
AuthorBilbily, John
AuthorHiemke, Christoph
AuthorLópez-Jaramillo, Carlos
AuthorMcGrane, Ian
AuthorLana, Fernando
AuthorEap, Chin B.
AuthorArrojo-Romero, Manuel
AuthorRǎdulescu, Flavian
AuthorSeifritz, Erich
AuthorEvery-Palmer, Susanna
AuthorBousman, Chad A.
AuthorBebawi, Emmanuel
AuthorBhattacharya, Rahul
AuthorKelly, Deanna L.
AuthorOtsuka, Yuji
AuthorLazary, Judit
AuthorTorres, Rafael
AuthorYecora, Agustin
AuthorMotuca, Mariano
AuthorChan, Sherry K.W.
AuthorZolezzi, Monica
AuthorOuanes, Sami
AuthorDe Berardis, Domenico
AuthorGrover, Sandeep
AuthorProcyshyn, Ric M.
AuthorAdebayo, Richard A.
AuthorKirilochev, Oleg O.
AuthorSoloviev, Andrey
AuthorFountoulakis, Konstantinos N.
AuthorWilkowska, Alina
AuthorCubała, Wiesław J.
AuthorAyub, Muhammad
AuthorSilva, Alzira
AuthorBonelli, Raphael M.
AuthorVillagrán-Moreno, José M.
AuthorCrespo-Facorro, Benedicto
AuthorTemmingh, Henk
AuthorDecloedt, Eric
AuthorPedro, Maria R.
AuthorTakeuchi, Hiroyoshi
AuthorTsukahara, Masaru
AuthorGründer, Gerhard
AuthorSagud, Marina
AuthorCelofiga, Andreja
AuthorIgnjatovic Ristic, Dragana
AuthorOrtiz, Bruno B.
AuthorElkis, Helio
AuthorPacheco Palha, António J.
AuthorLlerena, Adrián
AuthorFernandez-Egea, Emilio
AuthorSiskind, Dan
AuthorWeizman, Abraham
AuthorMasmoudi, Rim
AuthorMohd Saffian, Shamin
AuthorLeung, Jonathan G.
AuthorBuckley, Peter F.
AuthorMarder, Stephen R.
Available date2023-07-24T10:42:46Z
Publication Date2022-03-01
Publication NamePharmacopsychiatry
Identifierhttp://dx.doi.org/10.1055/a-1625-6388
CitationDe Leon, J., Schoretsanitis, G., Smith, R. L., Molden, E., Solismaa, A., Seppälä, N., ... & Müller, D. J. (2022). 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.
ISSN0176-3679
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85122150966&origin=inward
URIhttp://hdl.handle.net/10576/46238
AbstractThis 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.
Languageen
PublisherThieme
SubjectAmerican continental ancestry group
Asian continental ancestry group
clozapine/adverse effects
clozapine/blood
clozapine/metabolism
clozapine/therapeutic use
clozapine/toxicity
CYP1A2
drug labeling
European continental ancestry group
infection
inflammation
mortality/drug effects
Native
sex
smoking.
TitleAn International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels
TypeArticle
Pagination73-86
Issue Number2
Volume Number55
ESSN1439-0795
dc.accessType Open Access


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