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ClozapineAka: Clozaril

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  1. Class
    1. Atypical Antipsychotic (Second Generation agent)
    2. Neuroleptic
    3. Dibenzodiazepine Antipsychotic
  2. Precautions
    1. Not a first line Antipsychotic: See Disadvantages below
  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

Clozapine (C0009079)

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.
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)
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
MSHD003024
EnglishClozapine, CLOZAPINE PREPARATION
Spanishclozapina
Parent ConceptsCarbamazepine (C0006949), Benzodiazepines (C0005064), Hypnotics and Sedatives (C0020592), Dibenzazepines (C0012029), Antipsychotic Agents (C0040615), [CN709] ANTIPSYCHOTICS, OTHER (C0973508), Atypical antipsychotic (C1276996), Drug allergen (C1320237), Non-phenothiazines/ Atypicals (C1579416)
SourcesAOD, CSP, LNC, MSH, MTHSPL, NCI, NDFRT, RXNORM, SCTSPA, SNOMEDCT, USPMG, VANDF
Derived from the NIH UMLS (Unified Medical Language System)


Clozaril (C0719386)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
MSHD003024
EnglishClozaril
SourcesMSH, RXNORM
Derived from the NIH UMLS (Unified Medical Language System)



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