Clozapine

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"
• "Increased mortality in elderly patients with dementia-related psychosis"

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, alpha adrenergic, cholinergic muscarinic receptors, others

See Also

• Schizophrenia
• Bipolar disorder
• Borderline personality disorder
• Antipsychotic Medications

References

Authors

Ann Huang, Aaron Snyder, Ross Donaldson, Michael Holtz, Claire, Neil Young, Daniel Ostermayer