The major limitation in the use of clozapine for treatment of schizophrenia is

Clozapine:- It is the first atypical anti- psychotic. It has only weak D2 blocking action, produces few/no extrapyramidal symptoms; tardive dyskinesia is rare and prolactin level does not rise. Both positive and negative symptoms of schizophrenia are improved and clozapine is the most effective drug in refractory schizophrenia, i.e. patients not responding to typical neuroleptics may respond to it. Pharmacokinetics:- Clozapine is metabolized by CYP1A2, CYP2C19 & CYP3A4 into active and inactive metabolites with an average t 1/2 of 12 hours. Adverse effects:- It's major limitation is higher incidence of agranulocytosis (0.8%) and other blood dyscrasias: weekly monitoring of leucocyte count is required. Metabolic complication like weight gain, hyperlipidemia and precipitation of diabetes is another major limilation. Ref:- kd tripathi; pg num:-441