Global InformationClozapine information
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| Trade names | Clozaril, Leponex, Versacloz, others[1] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a691001 |
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| Routes of administration | By mouth, intramuscular injection |
| Drug class | Atypical antipsychotic |
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| Pharmacokinetic data | |
| Bioavailability | 60 to 70% |
| Metabolism | Liver, by several CYP isozymes |
| Elimination half-life | 4 to 26 hours (mean value 14.2 hours in steady state conditions) |
| Excretion | 80% in metabolized state: 30% biliary and 50% kidney |
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| ECHA InfoCard | 100.024.831 |
| Chemical and physical data | |
| Formula | C18H19ClN4 |
| Molar mass | 326.83 g·mol−1 |
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| Melting point | 183 °C (361 °F) |
| Solubility in water | 0.1889[5] |
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Clozapine is a psychiatric medication and is 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. It is also used for the treatment of psychosis in Parkinson's disease.[7][8]
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[9]) other antipsychotic has not had a satisfactory effect.[10][11][12][13][14][15][16] Long term follow-up studies from Finland show significant improvements in terms of overall mortality including from suicide and all causes.[17] Clozapine is on the World Health Organization's List of Essential Medicines.[18] It is available as a generic medication and so it is not usually promoted by pharmaceutical companies.[19] Common adverse effects include drowsiness, constipation, hypersalivation (increased saliva production), tachycardia, low blood pressure, blurred vision, weight gain, and dizziness.[19] 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.[20] Potential adverse effects include agranulocytosis, seizures, myocarditis (inflammation of the heart), hyperglycemia (high blood glucose levels), and constipation. The use of this drug can rarely result in clozapine-induced gastric hypomotility syndrome which may lead to bowel obstruction and death, and in older people with psychosis, as a result of dementia it may lead to an increased risk of death.[21][22] The mechanism of action is not entirely clear in the current medical literature.[19]
- ^ Cite error: The named reference
brandswas invoked but never defined (see the help page). - ^ "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.
- ^ 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.
- ^ "Clozaril- clozapine tablet". DailyMed. Retrieved 17 August 2021.
- ^ 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.
- ^ Stahl SM (16 May 2019). The clozapine handbook. Cambridge University Press. ISBN 978-1-108-44746-1. OCLC 1222779588.
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medicines.org.ukwas invoked but never defined (see the help page). - ^ Cite error: The named reference
National Institute for Health and Care Excellence (Great Britain)was invoked but never defined (see the help page). - ^ Cite error: The named reference
Kahn_2018was invoked but never defined (see the help page). - ^ Cite error: The named reference
Hasan_2012was invoked but never defined (see the help page). - ^ Cite error: The named reference
Buchanan_2010was invoked but never defined (see the help page). - ^ Cite error: The named reference
Gaebel_2005was invoked but never defined (see the help page). - ^ Cite error: The named reference
Kuipers_2014was invoked but never defined (see the help page). - ^ Cite error: The named reference
Howes_2017was invoked but never defined (see the help page). - ^ Cite error: The named reference
Galletly_2016was invoked but never defined (see the help page). - ^ 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.
- ^ Cite error: The named reference
Taipale_2020was invoked but never defined (see the help page). - ^ 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.
- ^ a b c Cite error: The named reference
AHFS2015was invoked but never defined (see the help page). - ^ 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.
- ^ 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.
- ^ "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.