HALF-LIFE: 5-16 hours STARTING DOSE: 12.5mg-25mg TARGET DOSING RANGE: 12.5mg-450mg PO BID BEST TIME TO DOSE: Evening (but BID dosing required until tolerated) HOW TO DOSE: >> Initial 12.5mg PO Once or Twice Daily >> Increase dose by 25mg-50mg per day to target dose of 300mg-450mg/day over 2-3 weeks >> If dosing >450mg/day then increase gradually by 50mg weekly >> Maximum dose is 900mg/day in 2-3 divided doses >> May take 1-6 months for response >> If dosing interrupted for >48 hours then restart titration PREGNANCY: AVOID (if possible) BREASTFEEDING: AVOID (if possible) FDA INDICATIONS: 1) Treatment-resistant schizophrenia (after 2 failed trials of antipsychotics) 2) Recurrent suicidal behavior in schizophrenia or schizoaffective disorders
Commonly used for aggression, violence, reatment resistant bipolar disorder
May reduce severity of tardive dyskinesia (controversial)
Agranulocytosis occurs in 0.5-2% of patients (Greatest risk within first 6 months)
Risk for seizures (especially at high doses), but lower risk with divided doses
Risk of myocarditis
Sedation common due to antagonism at M1, H1, and α1 receptors
Sialorrhea common due to clozapine being M4 agonist in salivary glands
Weight gain common due to antagonism at H1 and 5HT2C receptors
High cardio-metabolic risk (↑triglycerides, insulin resistance)
Risk for constipation, paralytic ileus, and/or Bowel Obstruction due to strong anticholinergic effects
Tachycardia from anticholinergic effects can be treated with propranolol
Orthostatic hypotension common due to antagonism of α1 receptors
Low risk of EPS/Prolactin elevation
Metabolized by CYP1A2, CYP2D6, and CYP3A4
Avoid using with benzodiazepines if possible
Avoid using with bone marrow suppressing agents (e.g., carbamazepine)
Recommended ANC Monitoring for Clozapine:
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