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Worldwide Differences in Regulations of Clozapine Use

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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.

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Authors and Affiliations

  1. Department of Psychiatry, Centre for Schizophrenia, Aalborg University Hospital, Brandevej 5, 9220, Aalborg, Denmark

    Jimmi Nielsen

  2. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Jimmi Nielsen

  3. Pharmacy Department, Waitemata District Health Board, Auckland, New Zealand

    Corina Young

  4. Faculty of Medicine, Transilvania University, Brasov, Romania

    Petru Ifteni

  5. Keio University School of Medicine, Tokyo, Japan

    Taishiro Kishimoto

  6. Faculty of Health Sciences, University of Macau, Macau SAR, China

    Yu-Tao Xiang

  7. Division for Specialised Treatment, Treatment Centre for Bipolar Disorders, Mental Health Service Organisation North Holland North, Alkmaar, The Netherlands

    Peter F. J. Schulte

  8. Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York, NY, USA

    Christoph U. Correll

  9. Pharmacy Department, Maudsley Hospital, London, UK

    David Taylor

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  1. Jimmi Nielsen
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  2. Corina Young
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  8. David Taylor
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Correspondence to Jimmi Nielsen.

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Conflicts of interest

Dr. 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, Bristol-Myers Squibb, Eli Lilly, Genentech, GersonLehrman Group, IntraCellular Therapies, Janssen/J&J, 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/J&J, National Institute of Mental Health (NIMH), Novo Nordisk A/S, Otsuka, Takeda, and the Thrasher Foundation. Corina Young, Petru Ifteni, Taishiro Kishimoto, Yu-Tao Xiang, Peter F. J. Schulte, and David Taylor report no conflicts of interest.

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Nielsen, J., Young, C., Ifteni, P. et al. Worldwide Differences in Regulations of Clozapine Use. CNS Drugs 30, 149–161 (2016). https://doi.org/10.1007/s40263-016-0311-1

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