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Clozapine

Aka: Clozapine, Clozaril
  1. Class
    1. Atypical Antipsychotic (Second Generation agent)
    2. Neuroleptic
    3. Dibenzodiazepine Antipsychotic
  2. 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
  3. Indications
    1. Refractory Schizophrenia
    2. Suicidal behavior in Schizophrenia
    3. Psychosis in the elderly (not FDA approved)
    4. Bipolar Disorder (not FDA approved)
  4. 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
  5. Cost
    1. Even generic costs >$250 per month
  6. Disadvantages
    1. Agranulocytosis has high mortality
    2. Higher risk of Diabetes Mellitus and weight gain
    3. Hypertriglyceridemia
  7. Adverse Effects
    1. Anticholinergic Symptoms
    2. Agranulocytosis
    3. Hypotension (alpha-Adrenergic Receptor blockade)
    4. Tachycardia
    5. Hyperthermia
    6. Hyperglycemia including development of Diabetes Mellitus
    7. Seizures
    8. Sialorrhea
    9. Weight gain
    10. Sedation
  8. 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
  9. Monitoring
    1. See Antipsychotic
    2. Absolute Neutrophil Counts
  10. Resources
    1. Clozapine REMS Program
      1. https://www.clozapinerems.com/CpmgClozapineUI/home.u
  11. References
    1. (2015) Presc Lett 22(11): 65
Medication Costs
clozapine (on 12/21/2016 at Medicaid.Gov Pharmacy Drug pricing)
CLOZAPINE 100 MG TABLET Generic $0.85 each
CLOZAPINE 200 MG TABLET Generic $2.23 each
CLOZAPINE 25 MG TABLET Generic $0.36 each
CLOZAPINE 50 MG TABLET Generic $0.69 each
CLOZAPINE ODT 100 MG TABLET Generic $6.08 each
clozaril (on 2/17/2017 at Medicaid.Gov Pharmacy Drug pricing)
CLOZARIL 100 MG TABLET Generic $0.85 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information.

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
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Clozaril (C0719386)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D003024
English clozaril, Clozaril
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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