clozapine: clinical use

Prescribing considerations

• Initiate and continue treatment through an appropriate specialist service with registration in the monitoring programme linked to the prescribed brand.
• Assess haematological, cardiac, metabolic, gastrointestinal, hepatic, neurological and smoking history.
• Actively prevent, identify and treat constipation; review constipating or anticholinergic medicines.
• Investigate persistent resting tachycardia, chest symptoms, breathlessness or unexplained flu-like illness.
• Urgently review smoking or caffeine changes, interacting medicines, severe infection or pneumonia.
• Coordinate formulation or brand changes with specialist pharmacy services.

Contraindications and cautions

• Inability to undergo required blood monitoring
• Previous clozapine-induced agranulocytosis or relevant toxic or idiosyncratic granulocytopenia
• Impaired bone-marrow function or concurrent medicines with substantial agranulocytosis potential
• Uncontrolled epilepsy
• Circulatory collapse, coma or significant central nervous system depression
• Severe renal or cardiac disease, including myocarditis
• Active or progressive liver disease or hepatic failure
• Paralytic ileus
• Hypersensitivity to clozapine or formulation excipients

Monitoring

• Full blood count, particularly absolute neutrophil count, under product and brand-specific monitoring requirements
• Symptoms of infection
• Pulse, blood pressure and symptoms of orthostatic hypotension
• Bowel function and gastrointestinal hypomotility symptoms
• Weight, glucose or HbA1c and lipid profile
• Liver function when indicated
• Clozapine plasma concentration when altered exposure or toxicity is suspected
• Sedation, seizures, swallowing problems and treatment interruptions

Clinical pharmacology

Clozapine has weak blockade at several dopamine receptors, greater affinity for D4 receptors, and serotonin, histamine, muscarinic and alpha-adrenergic antagonism. It is extensively metabolised, principally through CYP1A2 and CYP3A4. Food does not materially affect absorption.

Formulation and product differences

• Conventional tablets are swallowed; Zaponex orodispersible tablets disperse on the tongue and contain aspartame, which is relevant in phenylketonuria.
• Denzapine oral suspension must be shaken before measurement, uses oral dispensers and contains sorbitol and preservatives.
• Suspension can support people with swallowing difficulties, but accurate measurement is essential.
• Brands are linked to specific monitoring services, so switches should be coordinated.

Oral suspension

Route: Oral

Strengths: 50 mg/mL

Tablet

Route: Oral

Strengths: 25 mg, 50 mg, 100 mg, 200 mg