Worldwide Differences in Regulations of Clozapine

Authors: Jimmi Nielsen Corina Young Petru Ifteni Taishiro Kishimoto YuTao Xiang Peter F J Schulte Christoph U Correll David Taylor

Publish Date: 2016/02/16

Volume: 30, Issue: 2, Pages: 149-161

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Abstract

Clozapine remains the drug of choice for treatmentresistant schizophrenia As a consequence of its long history and complex pharmacology we suspected wide variation in the regulations of clozapine use across different countries The summaries of product characteristics SPCs from clozapine manufacturers as well as local and national guidelines in the following selected countries were reviewed China Denmark Ireland Japan The Netherlands New Zealand Romania the UK and the US Clozapine is available as tablets in all countries as an oral suspension in all included countries with the exception of Japan and Romania as orally disintegrating tablets in the US and China and as an injectable in The Netherlands General practitioner prescribing is only available in The Netherlands New Zealand the UK and the US although with some restrictions in some of the countries In Ireland and China clozapine is only dispensed through hospital pharmacies Hematological monitoring is mandatory in all countries but varies substantially in frequency eg in Denmark hematologic monitoring is mandatory weekly for 18 weeks followed by monthly monitoring compared with Japan where blood work is required weekly for 26 weeks followed by biweekly hematologic monitoring thereafter In most included countries with the exception of Denmark Romania and The Netherlands the manufacturer provides a mandatory hematological monitoring database and dispensing of clozapine is not permissible without acceptable white blood count and absolute neutrophil count results Local guidelines in New Zealand recommend echocardiography and routine troponin during the initial phases of treatment with clozapine Regulations of clozapine vary widely with regard to rules of prescribing and monitoring A worldwide update and harmonization of these regulations is recommendedDr Nielsen has received speaker honoraria from Hemocue Lundbeck and Bristol Myers Squibb and research grants from H Lundbeck and Pfizer Dr Correll has been a consultant and/or advisor to or has received honoraria from AbbVie Alkermes BristolMyers Squibb Eli Lilly Genentech GersonLehrman Group IntraCellular Therapies Janssen/JJ Lundbeck MedAvante Medscape Otsuka Pfizer ProPhase Roche Sunovion Supernus and Takeda He has also received grant support from the American Academy of Child and Adolescent Psychiatry BMS Janssen/JJ National Institute of Mental Health NIMH Novo Nordisk A/S Otsuka Takeda and the Thrasher Foundation Corina Young Petru Ifteni Taishiro Kishimoto YuTao Xiang Peter F J Schulte and David Taylor report no conflicts of interest

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