Clozapine

SGA / Dibenzodiazepine·Psychiatry - Antipsychotics

Treatment-resistant schizophrenia, reduction of suicidal behavior in schizophrenia

PBSSGA / TRSClozaril, Clopine200 mg tabletS4+1

Max Dose

900 mg/day

Neutrophils

STRICT LIMITS

Myocarditis

CRITICAL

Constipation

FATAL RISK

Rapid Summary

Overview

The most effective antipsychotic in existence. Reserved exclusively for Treatment-Resistant Schizophrenia (TRS). Fraught with lethal toxicities requiring intense national monitoring (CPMS).

Maximum Dose

Max 900 mg/day (Requires very slow, heavily monitored titration).

Clinical Focus

Lethal side effects include agranulocytosis, myocarditis, and fatal paralytic ileus (constipation). Never initiate outside a strictly controlled psychiatric setting.

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

The absolute last line of defense. The only antipsychotic proven to significantly reduce suicide rates.

Quick reference

Class & Role

SGA / Dibenzodiazepine — The most effective antipsychotic in existence.

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 daily. Titrate up by 25-50 mg/day as tolerated. Target 300-450 mg/day. Max 900 mg/day.

Key Indication Doses

Treatment Resistant Schizophrenia: Start PO 12.5 mg ONCE or TWICE daily. Titrate up by 25-50 mg/day as tolerated. 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 a patient misses exactly 48 HOURS of Clozapine, they lose their tolerance. You CANNOT restart their normal dose (it will cause cardiovascular collapse). You must re-titrate from 12.5 mg.

Best Uses

Avoid / Cautions

History of clozapine-induced agranulocytosis or myocarditis. Uncontrolled epilepsy. Paralytic ileus. Pregnancy Category C.

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