GENERIC NAME: clozapine BRAND NAME: Clozaril, Fazacio ODT DRUG CLASS AND MECHANISM: Clozapine is an anti-psychotic medication

that works by blocking receptors in the brain for several neurotransmitters (chemicals that nerves use to communicate with each other) including dopamine type 4 receptors, serotonin type 2 receptors, norepinephrine receptors, acetylcholine receptors, and histamine receptors. Unlike traditional anti-psychotic agents, such as chlorpromazine (Thorazine) and haloperidol (Haldol) as well as the newer anti-psychotics, risperidone (Risperdal) and olanzapine (Zyprexa), clozapine only weakly blocks dopamine type 2 receptors. INDICATION: CLOZARIL (clozapine) is indicated for the management of severely ill schizophrenic patients who fail to respond adequately to standard drug treatment for schizophrenia. Because of the significant risk of agranulocytosis and seizure associated with its use, CLOZARIL should be used only in patients who have failed to respond adequately to treatment with appropriate courses of standard drug treatments for schizophrenia, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. DOSING: Clozapine is given once, twice, or three times daily. The dose often is increased slowly until the optimal dose is found. The full effects of clozapine may not be seen until several weeks after treatment is begun. Adverse effects The use of clozapine is associated with side effects, many of which are minor, though some are serious and potentially fatal: the more common include extreme constipation, night-time drooling, muscle stiffness, sedation, tremors, orthostasis, hyperglycemia, and weight gain. The risks of extrapyramidal symptoms such as tardive dyskinesia are much less with clozapine when compared to the typical antipsychotics; this may be due to clozapine's anticholinergic effects. Extrapyramidal symptoms may subside somewhat after a person switches from another antipsychotic to clozapine. Clozapine also carries eleven black box warnings for agranulocytosis, CNS depression, leukopenia, neutropenia, seizure disorder, bone marrow suppression, dementia, hypotension, myocarditis, orthostatic hypotension and seizuresLowering of the seizure threshold may be dose related and slow initial titration of dose may decrease the risk for precipitating seizures. Slow titration of dosing may also decrease the risk for orthostatic hypotension and other adverse cardiovascular side effects. Clozapine may have a synergistic effect with the sedating action of other drugs such as benzodiazepines, and thus respiratory depression may result with concomitant use. Care should be taken, especially if the latter drugs are given parenterally. Many male patients have experienced cessation of ejaculation during orgasm as a side effect of clozapine, though this is not documented in official drug guides

Contraindications Clozapine is contraindicated in individuals with uncontrolled epilepsy, myeloproliferative disease, or agranulocytosis with prior clozapine treatment. Many other (relative) contraindications (e.g., preexisting cardiovascular or liver damage, epilepsy) also exist.

DRUG INTERACTIONS: Risperidone (Risperdal) may cause an increase in the amount of clozapine in the blood. This could lead to an increased risk of side effects from clozapine.