Known brand names include Clozaril.
An atypical (second-generation) antipsychotic taken by mouth as tablets. It is reserved for severe schizophrenia that has not responded to standard antipsychotics, and it also lowers the risk of repeated suicidal behavior in schizophrenia or schizoaffective disorder. Its boxed warnings include severe neutropenia, which requires regular blood counts, along with low blood pressure and fainting, seizures, and heart inflammation.
Exactly how clozapine works is unknown. It is thought to ease schizophrenia by blocking two brain receptors, dopamine D2 and serotonin 5-HT2A, which receive chemical messages passed between nerve cells. It also blocks receptors for histamine, adrenaline-type messengers, and acetylcholine, and it binds histamine and alpha-1 adrenaline receptors far more tightly than dopamine D2 receptors. It causes little or no rise in the hormone prolactin.
After a dose, blood levels peak in about 2.5 hours, and with steady use the body clears half of it in about 12 hours, almost entirely by breaking it down in the liver. Its blocking of adrenaline-type receptors likely adds to the drops in blood pressure, slow heart rate, and fainting that are most likely while the dose is first being raised. Its strong blocking of acetylcholine slows the gut, so constipation is common and can progress to a dangerous bowel blockage. Tobacco smoke speeds its breakdown, so quitting smoking can raise its level in the blood.
Clozapine is an antipsychotic for schizophrenia, a mental illness that disturbs a person's thinking, feelings, and behavior. It is used for severe schizophrenia that has not improved enough with standard antipsychotic medicines. It is also used to lower the chance of repeated suicidal behavior in people with schizophrenia or schizoaffective disorder, a related illness that combines psychotic symptoms with episodes of depression or mania, when they remain at ongoing risk. It helps control these illnesses but does not cure them.
It is taken by mouth as tablets, starting with a small amount that is raised slowly to limit dizziness and fainting. Because it can cause a severe drop in the white blood cells that fight infection, people taking it have their blood counts checked regularly. Its safety and effectiveness in children have not been established. It is not approved for older adults with psychosis caused by dementia, who face a higher risk of death on antipsychotics.
Sleepiness, heavy drooling, a fast heartbeat, dizziness, constipation, and weight gain are among the most common effects, and a passing fever can occur in the first 3 weeks. The boxed warnings cover severe neutropenia, a sharp drop in infection-fighting white blood cells, along with low blood pressure, slow heart rate, and fainting, seizures, inflammation or weakening of the heart muscle, and a higher risk of death in older adults with dementia. The label also warns about severe bowel slowing, liver injury, high blood sugar and cholesterol, heart rhythm changes, neuroleptic malignant syndrome, and blood clots in the lungs.
A clinician may order these while someone is taking it.
This is the boxed warning, the warning the FDA label prints first.
Severe neutropenia with a risk of serious, potentially fatal infection: get a baseline ANC and do not start if it is below 1500/μL (below 1000/μL with benign ethnic neutropenia). Orthostatic hypotension, bradycardia, syncope, and cardiac arrest, highest during initial titration and after interruptions; start at 12.5 mg once or twice daily and titrate slowly in divided doses. Dose-related seizures. Fatal myocarditis, pericarditis, and cardiomyopathy. Higher mortality in older adults with dementia-related psychosis.
Sources: [1]