|Clupeine||Cnicin||Coal Tar||Cobaltic Acetate||Cobaltic Fluoride|
|Systematic (IUPAC) name|
|Pregnancy cat.||C (AU) B (US)|
|Legal status||Prescription Only (S4) (AU) ℞-only (US)|
|Bioavailability||60 to 70%|
|Metabolism||Hepatic, by several CYP isozymes|
|Half-life||6 to 26 hours (mean value 14.2 hours in steady state conditions)|
|Excretion||80% in metabolized state: 30% biliary and 50% renal|
|Mol. mass||326.823 g/mol|
|Melt. point||183 °C (361 °F)|
|Solubility in water||0.1889 mg/mL (20 °C)|
|(what is this?)|
Clozapine is an atypical antipsychotic medication used in the treatment of schizophrenia, and is also sometimes used off-label for the treatment of bipolar disorder. The first of the atypical antipsychotics to be developed, it was first introduced in Europe in 1971, but was voluntarily withdrawn by the manufacturer in 1975 after it was shown to cause agranulocytosis, a condition involving a dangerous decrease in the number of white blood cells, that led to death in some patients. In 1989 after studies demonstrated that it was effective in treating treatment-resistant schizophrenia the United States Food and Drug Administration (FDA) approved the use of clozapine solely for that use, requiring regular white blood cell and absolute neutrophil counts. The FDA also requires clozapine to carry five black box warnings for agranulocytosis, seizures, myocarditis, for "other adverse cardiovascular and respiratory effects", and for "increased mortality in elderly patients with dementia-related psychosis." In 2002 the FDA approved clozapine for reducing the risk of suicidal behavior for patients with schizophrenia.
Clozapine is usually used only in patients that have not responded to other anti-psychotic treatments due to its danger of causing agranulocytosis as well as the costs of having to have blood tests continually during treatment. It is, however, one of the very effective anti-psychotic treatment choices. Patients are monitored weekly for the first six months. If there are no low counts the patient can be monitored every two weeks for an additional six months. Afterwards, the patient may qualify for every four-week monitoring. Clozapine has numerous severe side effects including agranulocytosis, bowel infarction, and seizures, and has been associated with myocarditis and diabetes though those relationships have not been confirmed. Additionally, it also often causes less serious side effects such as hypersalivation and weight gain.