Clozapine

Clozapine
Clinical data
Trade namesClozaril, others
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 mainly via CYP2D6
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
Chemical and physical data
FormulaC18H19ClN4
Molar mass326.83 g·mol−1
3D model (JSmol)
Melting point183 °C (361 °F)
Solubility in water0.1889
  • 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 Y
  • Key:QZUDBNBUXVUHMW-UHFFFAOYSA-N Y
  (verify)

Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily 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, clozapine is also approved for use in people with recurrent suicidal behavior in people with schizophrenia or schizoaffective disorder. It is also used for the treatment of psychosis in Parkinson's disease.

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) other antipsychotic has not had a satisfactory effect. Long term follow-up studies from Finland show significant improvements in terms of overall mortality including from suicide and all causes. Clozapine is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. Common adverse effects include drowsiness, constipation, hypersalivation (increased saliva production), tachycardia, low blood pressure, blurred vision, significant weight gain, and dizziness. 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. Serious adverse effects include agranulocytosis, seizures, myocarditis (inflammation of the heart), and hyperglycemia (high blood glucose levels). The use of clozapine may result rarely in clozapine-induced, gastric hypomotility syndrome, which may lead to bowel obstruction and death. The mechanism of action is not clear.