Clozapine (Clozaril)


Clinical Information


HALF-LIFE: 5-16 hours

STARTING DOSE: 12.5mg-25mg


BEST TIME TO DOSE: Evening (but BID dosing required until tolerated)


>> 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)


Side Effects

  • Constipation, dry mouth, blurry vision, tachycardia, orthostatic hypotension, urinary retention, agranulocytosis occurs in 0.5-2% of patients (Greatest risk within first 6 months), seizures (rare but may occur at high doses), small risk of myocarditis, sedation, sialorrhea (drooling, increased saliva production), weight gain, increased cardio-metabolic risk (↑triglycerides, insulin resistance)

Drug Interactions

  • Avoid using with benzodiazepines if possible
  • Avoid using with bone marrow suppressing agents (e.g., carbamazepine)

FDA Indications

  1. Treatment-resistant schizophrenia (after 2 failed trials of antipsychotics)
  2. Recurrent suicidal behavior in schizophrenia or schizoaffective disorders

Off Label Uses: For aggression, violence, and treatment resistant bipolar disorder; May reduce severity of tardive dyskinesia (controversial)

Mechanism(s) of Action

Clozapine is a weak dopamine 2 receptor antagonist. Clozapine also has actions at numerous other receptors including D1 receptors, serotonin 5HT2, histaminic receptors, and alpha adrenergic receptors. Interestingly, Clozapine’s antidopaminergic properties are more prominent in the cortical and limbic areas compared to the basal ganglia.


Absolute Neutrophil Monitoring (ANC) Schedule


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