【藥品性質提示】 根據 2019 AGS Beers Criteria，本藥品為【潛在不適當用藥 (PIM)】，不建議用於老年人 (除非用於思覺失調、雙極症、或化療止吐)。

思覺失調症
1. Treatment of severely ill patients with schizophrenia who fail to respond adequately to antipsychotic treatment
2. To reduce the risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for reexperiencing suicidal behavior, based on history and recent clinical state
#仿單變更2021

Second Generation (Atypical) Antipsychotic
The drug has demonstrated efficacy in the therapy of treatment-resistant schizophrenic patients. Because of the higher risk of agranulocytosis, clozapine should be reserved for those treatment-resistant patients who have not responded to adequate trials of other antipsychotic agents

Onset of action:
1. Bipolar disorder, acute mania: Initial effects may be observed within days of treatment with continued improvements over 1 to 2 weeks
2. Parkinson disease psychosis: Initial effects may be observed within 1 week with continued improvements over 2 to 3 months
3. Schizophrenia: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks
Distribution:
1. Protein binding: 97% to serum proteins
2. Bioavailability: 27% to 50% (not affected by food)
Metabolism:
Extensively hepatic via CYP1A2 (primary), 2C19, 3A4 and 2D6
Excretion:
Urine (~50%) and feces (30%) with trace amounts of unchanged drug
Half-life elimination:
12 hours

1. Serious hypersensitivity to clozapine or any component (eg, photosensitivity, vasculitis, erythema multiforme, SJS)
2. Myeloproliferative disorders
3. History of toxic or idiosyncratic agranulocytosis or severe granulocytopenia (unless due to previous chemotherapy)
4. Concomitant use with other agents that suppress bone marrow function
5. Active hepatic disease associated with nausea, anorexia, or jaundice; progressive hepatic disease or hepatic failure
6. Paralytic ileus
7. Uncontrolled epilepsy
8. Severe CNS depression or comatose states
9. Severe renal impairment
10. Severe cardiac disease (eg, myocarditis)
11. patients unable to undergo blood testing

B

Not recommended

1. Common adverse effects: Sedation, dry mouth, nausea, constipation (須特別留意的病人：正在使用其他"已知會導致便秘"的藥物)<20210301>, sialorrhea, cardiovascular events (hypertension, hypotension, tachycardia), fever
2. Serious adverse effects: Agranulocytosis (white blood cell counts should be monitored weekly for 6 months and every other week thereafter)
3. Postmarketing: Infection, GI effects (intestinal obstruction, ischemic bowel disease, intestinal ulcer, gastrointestinal perforation)<20210301>, DRESS(藥物疹合併嗜伊紅血症及全身性症狀)<20210301>

Schizophrenia:
1. Initial 12.5 mg once or twice daily; increase, as tolerated, in increments of 25 to 50 mg daily to a target dose of 300 to 450 mg daily by the end of 2 weeks
2. May further titrate in increments not exceeding 100 mg and no more frequently than once or twice weekly. Maximum total daily dose: 900 mg.
Note: The manufacturer recommends twice or three times daily dosing to minimize the risk of adverse effects.
Suicidal behavior in schizophrenia or schizoaffective disorder:
1. Initial: 12.5 mg once or twice daily; increased, as tolerated, in increments of 25 to 50 mg daily to a target dose of 300 to 450 mg daily (administered in divided doses) by the end of 2 weeks
2. May further titrate in increments not exceeding 100 mg and no more frequently than once or twice weekly. Mean dose is ~300 mg daily; maximum total daily dose: 900 mg.
Bipolar disorder (off-label):
Initial 25 mg daily; increase in 25 mg increments to a maximum dose of 550 mg/day. Usual daily dose ~100 to 300 mg/day.

Safety and effectiveness for use in children has not been established.
But for 12-17 y/o as an initial dose of 12.5 -25 mg/day and increased every 4 days by one or two times the starting dose has been reported.