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Objectives: To compare the prevalence, regulations, and pharmacovigilance practices of clozapine use in Eastern European countries (except Russia)., Methods: Questionnaires and data from administrative databases (2016 and 2021), package inserts and national guidelines were collected from 21 co-authors from 21 countries. Reports of clozapine adverse drug reactions (ADRs) sent to the global pharmacovigilance database (VigiBase™) were analyzed from introduction to December 31, 2022., Results: Clozapine prescription among antipsychotics in 2021 varied six-fold across countries, from 2.8 % in the Czech Republic to 15.8 % in Montenegro. The utilization of antipsychotics in both 2016 and 2021 was highest in Croatia, and lowest in Serbia in 2016, and Montenegro in 2021, which had half the defined daily dose (DDD)/1000/day compared to the Croatian data. From 2016 to 2021, the prevalence of antipsychotic use increased in almost all countries; the proportion of clozapine use mainly remained unchanged. Differences were detected in hematological monitoring requirements and clozapine approved indications. Only a few national schizophrenia guidelines mention clozapine-induced myocarditis or individual titration schemes. The VigiBase search indicated major underreporting regarding clozapine and its fatal outcomes. By comparison, the United Kingdom had less than half the population of these Eastern European countries but reported to VigiBase more clozapine ADRs by 89-fold and clozapine fatal outcomes by almost 300-fold., Conclusion: Clozapine is under-utilized in Eastern European countries. Introducing individualized clozapine treatment schedules may help to maximize clozapine benefits and safety. Major improvement is needed in reporting clozapine ADRs and fatal outcomes in Eastern European countries., Competing Interests: Declaration of competing interest In the last 3 years, MS participated in lectures for the following companies: Alkaloid, Angelini, Belupo, Gedeon Richter, Jadran Galenski Laboratorij, Johnson & Johnson, Lundbeck, Pliva, Stada and Viatris; participated in clinical trials for Krka and Boeringer Ingelheim; and is a member of the advisory board of Lundbeck. AW has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen-Cilag, Lundbeck, Polpharma, Sanofi and Valeant, and Termedia. MT participated in lectures for the following companies: Gedeon Richter, Johnson & Johnson, Lundbeck, Medochemie, Olainfarm, Grindex, and is a member of the advisory board of Biogen. MK participated in lectures for the following companies: Angeliny, Gedeon Richter, Johnson & Johnson, Lundbeck and is a member of the advisory board of Angeliny and Lundbeck. UP participated in lectures for the following companies: Krka, Lundbeck, Nobel, Sandoz, and Sun Pharmaceuticals. RM is a member of the advisory board of Johnson & Johnson, and gave lectures for Lundbeck and Gedeon Richter. AC participated in lectures for the following companies: Teva, Krka, Gedeon Richter, Bonifar, Lundbeck, and Janssen; and participated in a clinical trial for Krka. DIR developed lectures and presented clozapine lectures with the support of Viatris, Galenika and Remedica; she received speaker ́s honoraria from Teva Serbia, Krka, Alkaloid and Gooodwill. DB participated in lectures for the following companies: Angelini, Gedeon Richter, Johnson & Johnson, Krka, Lundbeck, Schwabe; participated in clinical trials for IQVIA, Johnson & Johnson, Otsuka Pharmaceuticals.In the last 3 years, the other authors report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)