4. SLIDE 4
• Clozapine is an Atypical antipsychotic.
• First of the antipsychotics to be developed by Sandoz in
1961.
• Introduced in Europe in 1971 and withdrawn in 1975.why?
• FDA approved clozapine for only treatment-resistant
schizophrenia
5. SLIDE 5Mechanism of action
• Clozapine is an antagonist of 5-HT2A, Di, D3, D4, and
a (especially a1) receptors. It has relatively low potency
as a D2 receptor antagonist. Data from PET scanning
show that whereas 1 0 mg of haloperidol produces 80
percent occupancy of striatal D2 receptors, clinically
effective dosages of clozapine occupy only 40 to 50
percent of striatal D2 receptors.
• This difference in D2 receptor occupancy is
probably why clozapine does not cause EPS.
7. Indications
SLIDE 7
Treatment-resistant schizophrenia
Tardive dyskinesia
Patients suffering from EPS (due to other class of
medications)
Treatment resistant mania
Psychotic depression
Idiopthic parkinsons disease
Suicide patients with schizophrenia
9. SLIDE 8
• Before initiating treatment with clozapine, a complete blood count
(CBC) with differential should be performed and the patient’s
general and cardiovascular health status should be evaluated.
• Treatment should be initiated at a low dose (12.5– 25 mg once or
twice daily) and increased gradually (by no more than 25–50
mg/day) as tolerated until a target dose is reached.
• The clozapine package label states that WBC and neutrophil counts
should be evaluated before treatment is initiated, weekly during the
first 6 months of treatment and at least every 2 weeks after 6
months of treatment.
• Clozapine treatment should not be initiated if the initial WBC count
is <3500/mm3
11. Dozages
SLIDE 10
Clozapine is available in 25 mg and 100 mg tablets. The
initial dosage is usually 25 mg one or two times daily,
although a conservative initial dosage is 1 2.5 mg twice
daily. The dosage can then be increased gradually (25 mg
a day every 2 or 3 days) to 300 mg a day in divided doses,
usually two or three times a day. Dosages up to 900 mg a
day can be used. Testing for blood concentrations of
clozapine may be helpful in patients who fail to respond.
Studies have found that plasma concentrations greater
than 350 μg/mL are associated with a better likelihood of
response.