An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels
Pharmacopsychiatry DOI: 10.1055/a-1625-6388This 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
...
Source: Pharmacopsychiatry - Category: Psychiatry Authors: de Leon, Jose Schoretsanitis, Georgios Smith, Robert L. Molden, Espen Solismaa, Anssi Sepp älä, Niko Kope ček, Miloslav Švancer, Patrik Olmos, Ismael Ricciardi, Carina Iglesias-Garcia, Celso Iglesias-Alonso, Ana Spina, Edoardo Ruan, Can-Jun Wang, Chua Tags: Review Source Type: research
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