Clozapine

Clozapine (中文:[[ ]])is an atypical antipsychotic or 2nd Generation antipsychotic medication. It is specifically used to treat treatment resistant schizophrenia (TRS), which affects approximately 1 in 3 people with the condition. These people include those who:

• Have tried at least 2 other antipsychotic medications that did not work
• Are unable to tolerae other antipsychotics because of their side-effects

It may also be used to treat psychoses secondary to Parkinson’s disease.

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Clozapine Tab 25 mg	CLOZ01	P1S1S3
Clozapine Tab 100 mg	CLOZ02	P1S1S3

Mechanism of Action

Clozapine has only weak dopamine-receptor-blocking activity at D1, D2, D3 and D5 receptors, but shows high potency for the D4 receptor. It is also an antagonist at the serotonin 5-HT2A receptors, improving depression, anxiety and the negative cognitive symptoms associated with schizophrenia.

Dosage

Indication	Dose
Schizophrenia	By mouth ADULT: ADULT (18 – 59 YEARS): 12.5 mg 1- 2 times daily on day 1, 25 – 50 mg on day 2 Then increased by 25 – 50 mg daily over 14 – 21 days up to 300 mg daily in divided doses Usual dose 200 – 450 mg daily Maximum 900 mg daily ADULT (≧ 60 years) 12.5 ng daily on day 1 25 – 37.5 mg on day 2, Then increased by 25 mg daily over 14 – 21 days up to 300 mg daily in divided doses, Usual dose 200 – 450 mg daily Maximum 900 mg daily
Psychosis in Parkinson’s disease	By mouth ADULT: 12.5 mg at bedtime Increased by 12.5 mg up to twice weekly Usual dose range 25 – 37.5 mg at bedtime Maximum 100 mg daily in 1 – 2 divided doses

DOSE ADJUSTMENTS DUE TO INTERACTIONS Dose adjustment may be necessary if smoking started or stopped during treatment.

How long will it take before clozapine begins to work? Some people feel the benefit of clozapine within a few days, others may need a few months or even a year.

• 1 in 3 people with TRS have an improvement within 6 weeks
• 2 in 3 people with TRS have an improvement after one year of treatment.

Side Effects

Clozapine is associated with a relatively high risk of low white blood cells. It specifically affects a type of white blood cell called neutrophil. Neutrophils help the body to fight infections. A small fall in neutrophil levels leads to a condition called neutropenia, while a big fall is called agranulocytosis. Agranulocytosis and neutropenia are uncommon. However, if they occur, it is usually within the first 18 weeks of clozapine treatment. It is recommended that the white blood cell count be regularly monitored.

All side-effects are listed by system organ and frequency:

• Very common (≥ 1/10)
• Common ( ≥ 1/100 to < 1/10)
• Uncommon (≥ 1/1000 to < 1/100)
• Rare (≥ 1/10,000 to < 1/1000)
• Very rare (<1/10,000)

Blood and lymphatic system disorders	Common: neutropenia Uncommon: agranulocytosis Rare: anaemia Very rare: thrombocytopenia
Metabolism and nutrition disorders	Common: weight gain Rare: diabetes mellitus
Psychiatric disorders	Common: dysarthria
Nervous system disorders	Very common: Drowsiness/sedation Dizziness Common: Seizures Extrapyramidal symptoms Akathisia Tremor Rigidity headache Uncommon: neuroleptic malignant syndrome Rare: confusion delirium
Eye disorders	Common: blurred vision
Cardiac disorders	Very common: tachycardia Common: ECG changes Rare: arrhythmias myocarditis pericarditis
Vascular disorders	Common: syncope postural hypotension hypertension
Gastrointestinal disorders	Very common: constipation hypersalivation Common: nausea vomiting anorexia dry mouth
Hepatobiliary disorders	Common: elevated liver enzymes Rare: pancreatitis hepatitis cholestatic jaundice
Renal and urinary disorders	Common: urinary retention