title: Worldwide Differences in Regulations of Clozapine Use.
abstract: Clozapine remains the drug of choice for treatment-resistant 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, e.g. 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 recommended.
authors.affiliation: Department of Psychiatry, Centre for Schizophrenia, Aalborg University Hospital, Brandevej 5, 9220, Aalborg, Denmark. jin@rn.dk.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. jin@rn.dk.
authors.forename: Jimmi
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Pharmacy Department, Waitemata District Health Board, Auckland, New Zealand.
authors.forename: Corina
authors.initials: C
authors.lastname: Young
authors.affiliation: Faculty of Medicine, Transilvania University, Brasov, Romania.
authors.forename: Petru
authors.initials: P
authors.lastname: Ifteni
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Taishiro
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: Yu-Tao
authors.initials: YT
authors.lastname: Xiang
authors.affiliation: Division for Specialised Treatment, Treatment Centre for Bipolar Disorders, Mental Health Service Organisation North Holland North, Alkmaar, The Netherlands.
authors.forename: Peter F J
authors.initials: PF
authors.lastname: Schulte
authors.affiliation: Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York, NY, USA.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: Pharmacy Department, Maudsley Hospital, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Taylor
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood / Q000627:therapeutic use*; D003024:Clozapine / Q000097:blood / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D004351:Drug Resistance; D004335:Drug and Narcotic Control; D016568:Drugs, Generic / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D038622:Internationality; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D016568:Drugs, Generic; D003024:Clozapine