SGA / Dibenzodiazepine·Psychiatry - Antipsychotics

cloZAPine

Treatment-resistant schizophrenia, reduction of suicidal behavior in schizophrenia

PBSSGA / TRSClozaril, Clopine200 mg tabletS4+1

At a glance

Max Dose

900 mg/day

Caution: Neutrophils

STRICT LIMITS

High risk: Myocarditis

CRITICAL

High risk: Constipation

FATAL RISK

Cautions

Avoid / Cautions

History of clozapine-induced agranulocytosis or myocarditis. Uncontrolled epilepsy. Paralytic ileus. Pregnancy Category C. Avoid concurrent carbamazepine (bone marrow suppression / fatal agranulocytosis risk).

Where it stands

Rapid Summary

Overview

Antipsychotic for treatment-resistant schizophrenia. Treatment requires registration and blood monitoring through the clozapine monitoring service because of serious, potentially fatal adverse effects.

Clinical Focus

Serious adverse effects include agranulocytosis, myocarditis and paralytic ileus, which can be fatal. Start only with the monitoring the WA guideline requires (see the WA Health section below).

Bottom Line

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but requires mandatory regular blood monitoring due to risk of fatal agranulocytosis and causes severe metabolic syndrome.

Formulation & Access

Brand Names

Clozaril, Clopine

Oral Routes

Tablets (12.5, 25, 50, 100, 200 mg). Oral liquid.

Prescribing & PBS

Highly Restricted. Prescriber, Pharmacist, and Patient MUST be registered with the Clozapine Patient Monitoring System (CPMS).

Indications & Use

Primary

PBSTGA

Treatment-resistant schizophrenia, reduction of suicidal behavior in schizophrenia.

Clinical Place

Reserved for treatment-resistant schizophrenia. Has evidence for reducing suicidal behaviour in schizophrenia.

Quick reference

Class & Role

SGA / Dibenzodiazepine. Used for treatment-resistant schizophrenia.

Route / Formulation

Tablets (12.5, 25, 50, 100, 200 mg). Oral liquid. (Clozaril, Clopine)

Usual Dose & Max

Start PO 12.5 mg once or twice on day 1, then 25-50 mg increments every 2-3 days as tolerated to avoid fatal collapse, orthostatic hypotension, or seizures. Target 300-450 mg/day. Max 900 mg/day.

Key Indication Doses

Treatment Resistant Schizophrenia: Start PO 12.5 mg once or twice on day 1, then 25-50 mg increments every 2-3 days as tolerated to avoid fatal collapse, orthostatic hypotension, or seizures. Target 300-450 mg/day. Max 900 mg/day. Elderly / Frail: Start PO 6.25 - 12.5 mg NOCTE. Titrate extremely slowly. Max 200 mg/day in elderly (extreme seizure and agranulocytosis risk at higher doses). Missed Dose Rule: If more than 48 hours since the last dose: psychiatric review before restarting, and re-titrate from 12.5 mg (see WA Health interruption guidance below).

Best Uses

Key Risks

Haematological: Agranulocytosis (1-2% risk, fatal if unmonitored). Cardiovascular: Myocarditis and Cardiomyopathy (highest risk in first 4-8 weeks), severe orthostatic hypotension, tachycardia. Gastrointestinal: Hypomotility leading to toxic megacolon, bowel ischemia, and fatal paralytic ileus. Severe hypersalivation (drooling). Neurological: Dose-dependent seizures (especially > 600mg/day), profound sedation.

Key Interactions

Smoking. Cigarette smoke heavily induces CYP1A2. If a patient stops smoking (e.g., admitted to hospital), their Clozapine levels will DOUBLE, causing seizures and coma. Dose must be reduced rapidly. Ciprofloxacin and Fluvoxamine (potent CYP1A2 inhibitors) spike clozapine levels.

Monitoring

Strict FBC monitoring via CPMS (Weekly for 18 weeks, then 4-weekly). Baseline and ongoing Troponin/CRP to monitor for myocarditis. Bowel chart tracking. Constipation on clozapine is a medical emergency. Check HR, BP, and temperature daily during titration.

Clinical Pearl

More patients die from clozapine-induced bowel ischemia (constipation) than from agranulocytosis. Every patient must be prescribed prophylactic laxatives (e.g., Movicol + Senna). Do not ignore a clozapine patient who hasn't opened their bowels in 3 days.

Access

Clozaril, Clopine200 mg tablet

Brand: Clozaril, Clopine
Formulation: Tablets (12.5, 25, 50, 100, 200 mg). Oral liquid.

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