Clozapine

Not to be confused with clonazepam or clonidine.

Clozapine
Skeletal formula of clozapine
Stick-and-ball model of the clozapine molecule
Clinical data
Trade namesClozaril, Leponex, Versacloz, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa691001
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, intramuscular
Drug classAtypical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60–70%
MetabolismLiver, by several CYP isozymes
Elimination half-life4–26 hours (mean value 14.2 hours in steady state conditions)
Excretion80% in metabolized state: 30% biliary and 50% kidney
Identifiers
  • 8-Chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.024.831 Edit this at Wikidata
Chemical and physical data
FormulaC18H19ClN4
Molar mass326.83 g·mol−1
3D model (JSmol)
Melting point183 °C (361 °F)
Solubility in water0.1889[5]
  • CN1CCN(CC1)C2=Nc3cc(ccc3Nc4c2cccc4)Cl
  • InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3 checkY
  • Key:QZUDBNBUXVUHMW-UHFFFAOYSA-N checkY
  (verify)

Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic (also called second-generation antipsychotic) to be discovered.[6] It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics, or who have been unable to tolerate other drugs due to extrapyramidal side effects. In the US the FDA authorisation also includes use for people with recurrent suicidal behaviour in people with schizophrenia or schizoaffective disorder.[7] It is also used for the treatment of psychosis in Parkinson's disease.[8][9]

Clozapine is recommended by multiple international treatment guidelines, after resistance to two other antipsychotic medications, and is the only treatment likely to result in improvement if two (or one[10]) other antipsychotic has not had a satisfactory effect.[11][12][13][14][15][16][17] Long term follow-up studies from Finland show significant improvements in terms of overall mortality including from suicide and all causes.[18] Clozapine is on the World Health Organization's List of Essential Medicines.[19] It is available as a generic medication and so it is not usually promoted by pharmaceutical companies.[20] Common adverse effects include drowsiness, constipation, hypersalivation (increased saliva production), tachycardia, low blood pressure, blurred vision, weight gain, and dizziness.[20] Clozapine is not normally associated with tardive dyskinesia (TD) and is recommended as the drug of choice when this is present, although some case reports describe clozapine-induced TD.[21] Serious adverse effects include agranulocytosis, seizures, myocarditis (inflammation of the heart), and hyperglycemia (high blood glucose levels). The use of this drug can rarely result in clozapine-induced gastric hypomotility syndrome which may lead to bowel obstruction and death.[22][23] The mechanism of action is not entirely clear in the current medical literature.[20]

  1. ^ Cite error: The named reference brands was invoked but never defined (see the help page).
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  4. ^ "Clozaril- clozapine tablet". DailyMed. Retrieved 17 August 2021.
  5. ^ Hopfinger AJ, Esposito EX, Llinàs A, Glen RC, Goodman JM (January 2009). "Findings of the challenge to predict aqueous solubility". Journal of Chemical Information and Modeling. 49 (1): 1–5. doi:10.1021/ci800436c. PMID 19117422.
  6. ^ Stahl SM, Meyer JM (16 May 2019). The Clozapine Handbook. Cambridge University Press. doi:10.1017/9781108553575. ISBN 978-1-108-44746-1. OCLC 1222779588.
  7. ^ "Information on Clozapine". Center for Drug Evaluation and Research (CDER). U.S. Food and Drug Administration. 9 August 2024.
  8. ^ Cite error: The named reference medicines.org.uk was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference National Institute for Health and Care Excellence (Great Britain) was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference Kahn_2018 was invoked but never defined (see the help page).
  11. ^ Cite error: The named reference Hasan_2012 was invoked but never defined (see the help page).
  12. ^ Cite error: The named reference Buchanan_2010 was invoked but never defined (see the help page).
  13. ^ Cite error: The named reference Gaebel_2005 was invoked but never defined (see the help page).
  14. ^ Cite error: The named reference Kuipers_2014 was invoked but never defined (see the help page).
  15. ^ Cite error: The named reference Howes_2017 was invoked but never defined (see the help page).
  16. ^ Cite error: The named reference Galletly_2016 was invoked but never defined (see the help page).
  17. ^ Remington G, Addington D, Honer W, Ismail Z, Raedler T, Teehan M (September 2017). "Guidelines for the Pharmacotherapy of Schizophrenia in Adults". Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 62 (9): 604–616. doi:10.1177/0706743717720448. PMC 5593252. PMID 28703015.
  18. ^ Cite error: The named reference Taipale_2020 was invoked but never defined (see the help page).
  19. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  20. ^ a b c Cite error: The named reference AHFS2015 was invoked but never defined (see the help page).
  21. ^ Pardis P, Remington G, Panda R, Lemez M, Agid O (October 2019). "Clozapine and tardive dyskinesia in patients with schizophrenia: A systematic review". Journal of Psychopharmacology. 33 (10): 1187–1198. doi:10.1177/0269881119862535. PMID 31347436. S2CID 198912192.
  22. ^ Hartling L, Abou-Setta AM, Dursun S, Mousavi SS, Pasichnyk D, Newton AS (October 2012). "Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis". Annals of Internal Medicine. 157 (7): 498–511. doi:10.7326/0003-4819-157-7-201210020-00525. PMID 22893011.
  23. ^ "Clozaril, Fazaclo ODT, Versacloz (clozapine): Drug Safety Communication - FDA Strengthens Warning That Untreated Constipation Can Lead to Serious Bowel Problems". FDA. 28 January 2020. Retrieved 30 January 2020.