Adult: Initially, 12.5 mg 1-2 times daily, increased in increments of 25-50 mg daily if tolerated, up to target dose of 300-450 mg daily within 2 weeks. Subsequent increments of up to 100 mg 1-2 times weekly. Max: 900 mg daily. Dosage and treatment recommendations may vary among countries and between individual products (refer to local or specific product guidelines).
Oral Schizophrenia
Adult: In patients who are unresponsive or intolerant to conventional antipsychotics, or who have severe neurological adverse effects with such drugs: 12.5 mg 1-2 times daily on Day 1, followed by 25 mg 1-2 times daily on Day 2. May gradually increase dose in increments of 25-50 mg up to 300 mg daily within 14-21 days. May further increase in increments of 50-100 mg 1-2 times weekly, if required. Usual dose range: 200-450 mg daily in divided doses. Max: 900 mg daily. Gradually reduce to a suitable maintenance dose once desired therapeutic response is achieved. Elderly: Initially, 12.5 mg on Day 1, increase subsequently in increments of up to 25 mg daily.
Oral Psychoses in Parkinson's disease
Adult: Initially, 12.5 mg once daily at bedtime. Dose may be increased in increments of 12.5 mg up to 2 times weekly according to response; a daily dose of 50 mg should not be reached before the end of the 2nd week. Usual dose: 25-37.5 mg daily. Use the lowest effective dose. Elderly: Initially, 12.5 mg on Day 1, increase subsequently in increments of up to 25 mg daily.
What are the brands available for Clozapine in Hong Kong?
Clozaril
Special Patient Group
Patients taking weak to moderate CYP1A2 (e.g. tobacco smoke) or CYP3A4 inducers: Dose increase may be necessary.
Patients taking strong CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin, enoxacin): Use 1/3 of the usual dose.
Patients taking strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin): Not recommended. If concomitant use is necessary, may increase dose of clozapine.
Pharmacogenomics:
Clozapine is almost completely metabolised by CYP450 enzymes, particularly CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Recent studies indicate a significant association between plasma concentrations of clozapine and clinical response. A subset of the population (3-10%) exhibits reduced CYP2D6 enzymatic activity and is classified as CYP2D6 poor metabolisers. Genotyping test may be considered prior to initiation of therapy.
CYP2D6 poor metabolisers
Patient may develop higher than expected plasma concentrations of clozapine when administered at standard doses. The US Food and Drug Administration (US FDA) approved label states that dose reduction may be necessary.
Renal Impairment
Severe: Contraindicated.
Administration
Clozapine May be taken with or without food.
Contraindications
History of toxic or idiosyncratic agranulocytosis or severe granulocytopenia (except cases caused by previous chemotherapy), impaired bone marrow function, uncontrolled epilepsy, circulatory collapse, CNS depression of any cause, severe cardiac disorders (e.g. myocarditis), paralytic ileus, alcoholic or toxic psychosis, drug intoxication, and comatose states. Hepatic (including active or progressive liver disease, and hepatic failure) and severe renal impairment. Concomitant use with long-acting depot antipsychotics and other agents causes bone marrow suppression.
Special Precautions
Patient with CV disease or family history of QT interval prolongation; cerebrovascular disease or risk factors for stroke; history of seizure; decreased gastrointestinal motility, visual problems, urinary retention; diabetes mellitus. Avoid abrupt withdrawal. Smokers (including cessation). CYP2D6 poor metabolisers. Renal and hepatic impairment. Elderly (not indicated for use in dementia-related psychosis). Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal ideation; orthostatic hypotension, bradycardia, syncope; anticholinergic effects (e.g. constipation, urinary retention, xerostomia, blurred vision, tachycardia); seizures, somnolence, motor and sensory instability that may lead to falls, fractures or other injuries; metabolic changes including dyslipidaemia (mainly manifested as hypercholesterolaemia and/or hypertriglyceridaemia, including acute pancreatitis), significant weight gain (≥7% from baseline weight); extrapyramidal symptoms (e.g. akathisia, dystonia, tardive dyskinesia, drug-induced parkinsonism); haematologic abnormalities (e.g. leucopenia, neutropenia, thrombocytopenia); drug-induced fever, sialorrhoea and drooling. Blood and lymphatic system disorders: Eosinophilia, leucocytosis. Ear and labyrinth disorders: Vertigo. Gastrointestinal disorders: Nausea, vomiting, dyspepsia, dry mouth. General disorders and administration site conditions: Fatigue. Investigations: Elevated liver enzymes. Metabolism and nutrition disorders: Anorexia. Nervous system disorders: Headache, dizziness, drowsiness, sedation, tremor. Psychiatric disorders: Dysarthria, insomnia, agitation, confusion, restlessness. Renal and urinary disorders: Urinary incontinence. Skin and subcutaneous tissue disorders: Diaphoresis, skin rash. Vascular disorders: Hypertension. Potentially Fatal: Severe agranulocytosis or neutropenia; myocarditis, pericarditis, cardiomyopathy; MI, QT prolongation or risk for torsade de pointes; DVT, pulmonary embolism; hepatotoxicity, including fulminant hepatic failure and hepatitis; neuroleptic malignant syndrome (NMS); gastrointestinal hypomotility resulting in paralytic ileus, intestinal obstruction, faecal impaction, and gastrointestinal infarction, necrosis or perforation; cerebrovascular effects (e.g. CVA, TIA); temperature dysregulation which may lead to heatstroke (particularly during a heat wave or strenuous exercise) and hypothermia; hyperglycaemia and exacerbation of diabetes occasionally associated with ketoacidosis or coma.
Patient Counseling Information
This drug may cause drowsiness, sedation, and seizures, if affected, do not drive or operate machinery.
Monitoring Parameters
Obtain WBC counts and ANC within 10 days before treatment initiation (findings must be ≥3500/mm3 WBC count and ≥2000/mm3 ANC), weekly for the 1st 18 weeks, then at least every 4 weeks throughout the treatment, and for 4 weeks after complete discontinuation of therapy. Recommended monitoring parameters for WBC count and ANC may vary among countries and between individual products (refer to local or specific product guidelines for detailed information). Evaluate mental status, alertness, adherence, fall risk, bowel function (every visit); history of metabolic syndrome (annually); smoking patterns (regularly). Perform ECG (at baseline, then repeat after significant dose changes) and echocardiogram (at baseline, then repeat if signs or symptoms of myocarditis occur) in patients who have cardiac risk factors. Monitor serum clozapine concentration (as clinically indicated); C-reactive protein, eosinophils, troponin (weekly during 1st 6 weeks of therapy or if signs or symptoms of myocarditis occur); electrolyte levels, renal and liver function, TSH (annually); blood pressure, temperature, pulse rate (at least weekly during 1st 3-4 weeks of therapy and 4 weeks after dose changes); weight, height, BMI (8-12 weeks after treatment initiation and dose changes, then quarterly thereafter); prolactin level (if symptoms are reported); fasting blood glucose or HbA1c, lipid panel (4 months after treatment initiation and annually; check more frequently than annually if abnormal). Assess for signs and symptoms of any kind of infection (e.g. fever, sore throat, or other flu-like symptoms); myocarditis (e.g. chest pain, sinus tachycardia, palpitations, dyspnoea); extrapyramidal symptoms (every visit, 4 weeks after starting treatment, every dose changes, and annually); tardive dyskinesia (every visit and annually).
Management: Symptomatic and supportive treatment. Perform gastric lavage or administer activated charcoal within 6 hours after ingestion. Establish and maintain an airway; ensure adequate ventilation and oxygenation. Avoid the use of epinephrine in the treatment of hypotension. Continuously monitor cardiac status, vital signs, electrolytes, and acid-base balance.
Drug Interactions
Increased risk and severity of bone marrow suppression with other bone marrow suppressants (e.g. carbamazepine, chloramphenicol), long-acting depot injections of antipsychotics, sulfonamides (e.g. cotrimoxazole), pyrazolone analgesics (e.g. phenylbutazone), penicillamine, and cytotoxic agents. Concurrent use with benzodiazepines may increase the risk of circulatory collapse, that may result in cardiac and/or respiratory arrest. Additive anticholinergic activity with anticholinergic agents. May potentiate the hypotensive effects of antihypertensives. Enhanced central effect and CNS depression with MAOIs, CNS depressants, including benzodiazepine and narcotics. May increase the plasma concentration of highly protein bound substances (e.g. warfarin, digoxin). Reduced plasma concentration with phenytoin. Increased risk of NMS with lithium. Increased plasma level with CYP1A2 inhibitors (e.g. ciprofloxacin, fluvoxamine, perazine, oral contraceptives, caffeine). Decreased plasma level with CYP1A2 inducers (e.g. omeprazole).
Food Interaction
May enhance CNS depressant effect with alcohol.
Action
Description: Mechanism of Action: Clozapine, a dibenzodiazepine derivative, is an atypical or 2nd- generation antipsychotic agent. Its exact mechanism of action is unknown; however, it may be mediated through combined antagonism of dopamine (D2) and serotonin type 2A (5-HT2A) receptors. Additionally, clozapine possesses α-adrenergic blocking, antihistaminic, antimuscarinic, antiserotonergic, and sedative activities. Onset: Schizophrenia: Within 1 to 2 weeks (initial effects). Duration: Variable. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: Approx 27-50%. Time to peak plasma concentration: Tablet: 2.5 hours (range: 1-6 hours); orally disintegrating tablets: 2.3 hours (range: 1-6 hours); oral suspension: 2.2 hours (range: 1-3.5 hours). Distribution: Enters breast milk. Plasma protein binding: Approx 95%. Metabolism: Almost completely metabolised by CYP1A2 and CYP3A4, and to some extent by CYP2C19 and CYP2D6 via N-demethylation, hydroxylation and N-oxidation, forming desmethyl metabolite (active), hydroxylated and N-oxide derivatives. Excretion: Mainly via urine (approx 50%) and faeces (30%) as metabolites and trace amounts of unchanged drug. Terminal elimination half-life: Approx 12 hours (range: 4-66 hours).
Chemical Structure
Clozapine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135398737, Clozapine. https://pubchem.ncbi.nlm.nih.gov/compound/Clozapine. Accessed Nov. 26, 2025.
Storage
Store between 20-25°C. Orally disintegrating tab: Protect from moisture. Oral suspension: Protect from light. Do not freeze or refrigerate. Use within 100 days after initial opening of the bottle.
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