Editing Clozapine (section)

==== International Variation and Cost effectiveness of Monitoring ====
There is very significant international variation in the frequency of full blood count (for neutrophil counts) monitoring including both the thresholds for increased monitoring and for clozapine withdrawal as well as the duration and frequency of blood testing. The most extreme variation is between Iceland, where clozapine is given without full blood monitoring, and with no demonstrable increase in risk and Japan, where the thresholds and frequency is highest. Likewise there are differences between the US thresholds and those in the UK. The US and UK thresholds for clozapine monitoring were identical until 2015, at which point the US Food and Drug Administration (FDA) approved a reduction of 0.5 × 10<sup>−9</sup>/L for each ANC range and removed the requirement for white blood cell, eosinophil and platelet monitoring completely. The frequency used in many parts of mainland Europe and the reduced US thresholds and alternate, extended intervals in monitoring used in the Netherlands have had no demonstrable increase in risk.<ref>{{cite journal | vauthors = Oloyede E, Blackman G, Whiskey E, Bachmann C, Dzahini O, Shergill S, Taylor D, McGuire P, MacCabe J | title = Clozapine haematological monitoring for neutropenia: a global perspective | journal = Epidemiology and Psychiatric Sciences | volume = 31 | pages = e83 | date = November 2022 | pmid = 36426600 | doi = 10.1017/s204579602200066x | pmc = 9714212 }}</ref><ref>{{cite journal | vauthors = Ingimarsson O, MacCabe JH, Haraldsson M, Jónsdóttir H, Sigurdsson E | title = Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland | journal = BMC Psychiatry | volume = 16 | issue = 1 | pages = 441 | date = December 2016 | pmid = 27955666 | doi = 10.1186/s12888-016-1167-0 | doi-access = free | pmc = 5153901 }}</ref><ref name="Understanding clozapine-related blo"/> The rationale for monitoring after the first 18 weeks of treatment is questionable, given that monthly blood sampling is highly unlikely to detect the sudden and profound falls in ANC that accompany agranulocytosis<ref name="Distinctive pattern of neutrophil c"/> and the economic analysis of the cost effectiveness of the current clozapine monitoring schedules shows that these are of highly questionable utility.<ref>{{cite journal | vauthors = Girardin FR, Poncet A, Blondon M, Rollason V, Vernaz N, Chalandon Y, Dayer P, Combescure C | title = Monitoring white blood cell count in adult patients with schizophrenia who are taking clozapine: a cost-effectiveness analysis | journal = The Lancet. Psychiatry | volume = 1 | issue = 1 | pages = 55–62 | date = June 2014 | pmid = 26360402 | doi = 10.1016/s2215-0366(14)70245-7 }}</ref> Similarly several other drugs, for example carbimazole, which is   commonly used in medical practice and with very similar risks of agranulocytosis is  used without mandatory FBC monitoring.<ref name="Non-chemotherapy drug-induced neutr"/><ref>{{cite journal | vauthors = Vicente N, Cardoso L, Barros L, Carrilho F | title = Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management | journal = Drugs in R&D | volume = 17 | issue = 1 | pages = 91–96 | date = March 2017 | pmid = 28105610 | doi = 10.1007/s40268-017-0172-1 | pmc = 5318340 }}</ref>