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
- Schizophrenia (limited data - adjusted dose based on tolerability, clinical response)
- Children >6 years PO 6.25 or 12.5mg qd
- Adolescents 12.5mg 1-2x daily
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
- Adult
- Hepatic Dosing
- Adult
- not defined, consider decreasing dose for significant impairment
- Pediatric
- not available
- Adult
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
- Schizophrenia
- Bipolar disorder
- Borderline personality disorder
- Antipsychotics
- Antipsychotic toxicity