clozapine CLOZARIL

Class: Second Generation Antipsychotic/​Benzazepine Derivative
FDA Indications: Treatment-Resistant Schizophrenia, Reduction In The Risk Of Recurrent Suicidal Behavior In Schizophrenia Or Schizoaffective Disorders
Off-Label Use: Treatment-refractory Bipolar Disorder, Impulse Control Disorders, Borderline Personality Disorder, Aggression And Violence In Psychotic Patients, Parkinsons Disease Psychosis, Lewy Body Dementia, Parkinsonian Tremor
Forms: 25, 100mg tablet; 12.5, 25, 50, 100mg ODT
Dose Range: 100-900 mg/day
Starting: 12.5 mg QD or BID, and ↑ gradually by 25-50 mg/day to target dose of 300-450 mg after 2 weeks. Maximum recommended dose is 900 mg/day divided TID.
Stopping: Taper 6-8 weeks, rapid d/c can lead to rebound psychosis
Monitoring: Clozapine REMS

NAMI drug fact sheet

Contraindications: Neutropenia, Seizures, Cardiac disease
Serious Side Effects: , , , , potentially fatal agranulocytosis (0.8%), clozapine-induced myocarditis (0.2%), Insulin resistance and diabetes mellitus, diabetic ketoacidosis, and adynamic ileus
Possible Risk of TdP, Drugs to Avoid in Congenital Long QT
Side Effects: leukopenia (3%), hypersalivation, urinary incontinence, sedation/somnolence, constipation, dizziness, tachycardia, weight gain
1° MOA: 5HT2A–D2 antagonist
Target: Antagonism at: Partial agonist at Postsynaptic 5HT1A
t½: 12 (9-17)° TMAX: 2.5°
Substrate of: 1A2, 3A4
Inhibits: ∅ ; Induces:
Active Metabolites: N-Desmethylclozapine, clozapine N-oxide
  • - the prototype of second-generation atypical antipsychotics
  • - considered a "Fast-Off-D2 Antipsychotic" d/t its tendancy towards faster dissociation from the D2 receptor, which likely explains why it causes little or no prolactin elevation, EPS, or tardive dyskinesia
  • - most efficacious atypical antipsychotic agent in patients with treatment-resistant schizophrenia
  • - the only antipsychotic that has been documented to reduce the risk of suicide in schizophrenia
  • - weight gain is the highest among SGAs except olanzapine; the average weight gain is 30 pounds, usually occurring in the first 6-12 months
  • - higher incidence of sedation and seizures (5%) than other SGAs
  • - augmentation with valproate can improve efficacy
  • - good evidence for treating violence
Special Populations

Category B—There are insufficient data to identify risks related specifically to clozapine use during pregnancy.

It may be concentrated in the breast milk; however, RID is unknown. Given the severity of adverse events associated with clozapine exposure in adults, its use should be reserved for those with treatment-refractory illness, and monitoring of white blood cell counts in the nursing infant is mandatory

All atypicals may increase mortality in elderly patients by 1.7 times greater than placebo. In the older adult, the titration may need to be slower, and maintenance doses are typically in the 100 to 150 mg/day range.

2019 BEE℞S Recommendation: Avoid, except in schizophrenia or bipolar disorder. Increased risk of CVA and greater rate of cognitive decline and mortality in persons with dementia. Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacological options have failed or are not possible and the older adult is threatening substantial harm to self or others.

There are no dosage adjustments required

There are no dosage adjustments required


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Last updated February 29 2024 20:54:18. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.