CLOZAPINE

Indications & Dose:

Schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs

•  BY MOUTH

Adult 18–59 years: 12.5 mg 1–2 times a day for day 1, then 25–50 mg for day 2, then increased, if tolerated, in steps of 25–50 mg daily, dose to be increased gradually over 14–21 days, increased to up to 300 mg daily in divided doses, larger dose to be taken at night, up to 200mg daily may be taken as a single dose at bedtime; increased in steps of 50–100 mg 1–2 times a week if required, it is preferable to increase once a week; usual dose 200–450 mg daily, max. 900mg per day, if restarting after interval of more than 48 hours, 12.5 mg once or twice on first day (but may be feasible to increase more quickly than on initiation)—extreme caution if previous respiratory or cardiac arrest with initial dosing

Adult 60 years and over: 12.5 mg once daily for day 1, then increased to 25–37.5 mg for day 2, then increased, if tolerated, in steps of up to 25 mg daily, dose to be increased gradually over 14–21 days, increased to up to 300 mg daily in divided doses, larger dose at to be taken night, up to 200mg daily may be taken as a single dose at bedtime; increased in steps of 50–100 mg 1–2 times a week if required, it is preferable to increase once a week; usual dose 200–450 mg daily, max. 900mg per day, if restarting after interval of more than 48 hours, 12.5 mg once or twice on first day (but may be feasible to increase more quickly than on initiation)—extreme caution if previous respiratory or cardiac arrest with initial dosing

Psychosis in Parkinson’s disease

•  BY MOUTH

Adult: 12.5 mg once daily, dose to be taken at bedtime, then increased in steps of 12.5 mg up to twice weekly, adjusted according to response; usual dose 25–37.5 mg once daily, dose to be taken at bedtime; increased in steps of 12.5 mg once weekly, this applies only in exceptional cases, increased if necessary up to 100 mg daily in 1–2 divided doses; Usual maximum 50 mg/24 hours 

Contraindications:

Myeloproliferative disorders, uncontrolled epilepsy, history of clozapine induced agranulocytosis or severe granulocytopenia, severe CNS depression, comatose states, narrow angle glaucoma 

Side Effects:

Cautions:

Precautions:

Cardiovascular disease, pulmonary disease, elderly, prostatic enlargement, hepatic disease, renal disease, general anesthesia, seizure disorders 

Interaction:

Drugs

Carbamazepine, phenytoin, primadone, valproic acid: Considerable reduction in plasma clozapine concentrations

Cimetidine, clarithromycin, troleandornycin: Increased serum clozapine concentrations

Diazepam: Isolated cases of cardiorespiratory collapse have been reported

Epinephrine: Reversed pressor effects of epinephrine

Erythromycin: Increased serum clozapine concentrations

Fluvoxamine: Marked increase in plasma clozapine concentrations and side effects; increased risk of leukocytosis

Warnings:

Adverse Effects:

Lactations:

 May be excreted in breast milk, avoid breast feeding during clozapine therapy 

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

CNS: Agitation, akathisia, akinesia, anxiety, ataxia,

confusion, depression, disturbed sleep, dizziness, drowsiness, epileptiform movements, fatigue, headache, hyperkinesia, hypokinesia, insomnia, lethargy, myoclonic jerks, nightmares, restlessness, rigidity, sedation, seizures, slurred speech, syncope, tremor, vertigo, weakness

CV: Angina, cardiac abnormality, chest pain, ECG change, hypertension, hypotension, tachycardia

EENT: Blurred vision

GI: Abdominal discomfort, anorexia, constipation, diarrhea, dry mouth, heartburn, LFT abnormality, nausea, salivation, vomiting

GU: Abnormal ejaculation; incontinence; urinary urgency, frequency, retention

HEME: Agranulocytosis, eosinophilia, leukopenia, neutropenia

SKIN: Rash

MISC: Fever, weight gain 

Patient And Carer Advice: