II. Class

  1. Atypical Antipsychotic (Second Generation agent)
  2. Neuroleptic
  3. Dibenzodiazepine Antipsychotic

III. Precautions

  1. Not a first line Antipsychotic: See Disadvantages below
  2. Only providers in Clozapine REMS Program can prescribe
    1. Each patient on Clozapine must be registered with the program
    2. Requires regular submission of Absolute Neutrophil Counts
  3. FDA black box warnings
    1. Agranulocytosis
    2. Seizure risk, Myocarditis
    3. Orthostatic Hypotension
    4. Increased mortality in elderly

IV. Indications

  1. Refractory Schizophrenia
  2. Suicidal behavior in Schizophrenia
  3. Psychosis in the elderly (not FDA approved)
  4. Bipolar Disorder (not FDA approved)

V. Dosing

  1. Adults
    1. Initial: 12.5 mg PO qd or bid
    2. Titrate slowly upwards in increments of 25-50 mg/day
    3. Target dosing: 300-450 mg/day
    4. Maximum dose: 900 mg/day
  2. Elderly
    1. Initial: 6.5 PO qd
    2. Titrate slowly upwards in increments of 25 mg/day
    3. Maximum dose: 450 mg/day

VI. Cost

  1. Even generic costs >$250 per month

VII. Disadvantages

  1. Agranulocytosis has high mortality
  2. Higher risk of Diabetes Mellitus and weight gain
  3. Hypertriglyceridemia

VIII. Adverse Effects

IX. Drug Interactions

  1. Increase Antipsychotic levels (toxicity risk): Monitor for toxicity
    1. Grapefruit juice
    2. Caffeine
    3. Cimetidine
    4. Ciprofloxacin
    5. Citalopram
    6. Erythromycin
    7. Fluoxetine
    8. Fluvoxamine
    9. Paroxetine
    10. Sertraline
  2. Decrease Antipsychotic levels (lower efficacy)
    1. Barbiturates
    2. Carbamazepine
    3. Phenytoin
    4. Nicotine
    5. Rifampin

XI. Resources

XII. References

  1. (2015) Presc Lett 22(11): 65

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Cost: Medications

clozapine (on 7/20/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
CLOZAPINE 100 MG TABLET Generic $0.90 each
CLOZAPINE 200 MG TABLET Generic $2.25 each
CLOZAPINE 25 MG TABLET Generic $0.39 each
CLOZAPINE 50 MG TABLET Generic $0.75 each
CLOZAPINE ODT 100 MG TABLET Generic $5.71 each
clozaril (on 2/5/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
CLOZARIL 100 MG TABLET Generic $0.90 each
CLOZARIL 25 MG TABLET Generic $0.39 each

Ontology: Clozapine (C0009079)

Definition (CHV) a drug used to treat schizophrenia
Definition (NCI) A synthetic dibenzo-diazepine derivative, atypical antipsychotic Clozapine blocks several neurotransmitter receptors in the brain (dopamine type 4, serotonin type 2, norepinephrine, acetylcholine, and histamine receptors). Unlike traditional antipsychotic agents, it weakly blocks dopamine type 2 receptors. It relieves schizophrenic symptoms (hallucinations, delusions, dementia). (NCI04)
Definition (MSH) A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.
Definition (CSP) tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent; binds several types of central nervous system receptors, and displays a unique pharmacological profile; it is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype, and also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity; agranulocytosis is a major adverse effect associated with administration of this agent.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D003024
SnomedCT 387568001, 96221003
LNC LP17236-8, MTHU004254
English 5H-Dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-, clozapine, clozapine (medication), CLOZAPINE, Clozapine [Chemical/Ingredient], cloZAPine, CloZAPine, 8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine, Clozapine, Clozapine (product), Clozapine (substance)
Swedish Klozapin
Czech klozapin
Finnish Klotsapiini
Russian LEPONEKS, KLOZAPIN, AZALEPTIN, АЗАЛЕПТИН, КЛОЗАПИН, ЛЕПОНЕКС
Japanese クロザピン
Croatian KLOZAPIN
Polish Klozapina
Spanish clozapina (producto), clozapina (sustancia), clozapina, Clozapina
French Clozapine
German Clozapin
Italian Clozapina
Portuguese Clozapina

Ontology: Clozaril (C0719386)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D003024
English clozaril, Clozaril