Clozapine

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General

  • Type: Atypical antipsychotic
  • Dosage Forms:
    • 12.5, 25, 50, 100, 200
    • 12.5, 25, 50, 100, 150, 200 ODT
  • Common Trade Names: Clozaril, FezaClo, Versacloz

Adult Dosing

Schizophrenia, resistant

  • 150-300mg PO BID
  • start: 12.5mg PO QD-bid, increase by 25-50mg/day to target 300-450mg/day in divided doses by day 14; then may increase by up to 100mg/day q3-7days;
  • max 900mg/day
  • retitrate from 12.5mg PO QD-bid if treatment interrupted > 2 d
  • taper dose over 1-2 weeks to DC

Suicide prevention, schizophrenia-associated

  • 150-300mg PO BID
  • start, increase, retitrate, and DC as above

Pediatric Dosing

  • not available

Special Populations

  • Pregnancy Rating: B (no evidence of risk)
  • Lactation: possibly unsafe
  • Renal Dosing
    • Adult
      • not defined, consider decreasing dose for significant impairment
    • Pediatric
      • not available
  • Hepatic Dosing
    • Adult
      • not defined, consider decreasing dose for significant impairment
    • Pediatric
      • not available

Indications

  • Controls positive and negative symptoms of psychotic disorders
  • Used for schizophrenia
  • Off label use:
    • Bipolar disorder
    • Borderline personality disorder

Contraindications

  • Allergy to class/drug
  • history of clozapine-associated myocarditis
  • history of agranulocytosis or granulocytopenia
  • uncorrected electrolyte abnormalities
  • caution in elderly, stroke, dementia, CAD, prolonged QT
  • caution if history of torsades de pointes, ventricular arrhythmias
  • caution if bradycardic, recent MI, CHF
  • caution if eosinophila
  • caution if pulmonary disease, hepatic impairment, seizure risk
  • caution if BPH, angle-closure glaucoma, DM
  • caution if PKU

Adverse Reactions

  • QT prolongation
  • Myocarditis
  • Agranulocytosis in 1%–2% of patients during initial treatment 3 months
    • Highest ~3 months into treatment and then decreases
  • Other potential side effects:
    • Dyslipidemia
    • Diabetes
    • Decreased seizure threshold
  • "Other adverse cardiovascular and respiratory effects" [1]
  • "Increased mortality in elderly patients with dementia-related psychosis"[1]

Pharmacology

  • Half-life: 4-66h
  • Metabolism: liver extensively
  • Excretion: urine 50%, feces 30%
  • Mechanism of Action: exact mechanism of action unknown, antagonizes dopamine D2, serotonin 5-HT2, α adrenergic, cholinergic muscarinic receptors, others

See Also

References

  1. 1.0 1.1 "Clozaril (Clozapine) drug description - FDA approved labeling for prescription drugs and medications at RxList". Rxlist.com. Retrieved 2008-10-09.