Clozapine

Indications
 Oral
Schizophrenia
Adult: 12.5 mg 1-2 times on day 1 followed by 25 mg 1-2 times on day 2, increased gradually in increments of 25-50 mg up to a daily dose of 300 mg within 14-21 days. Subsequent increments of 50-100 mg may be made 1-2 times wkly. Usual dose: 200-450 mg/day. Max: 900 mg/day.
Elderly: Initially, 12.5 mg on day 1 increased subsequently by increments of 25 mg.
Renal impairment: Mild-moderate renal impairment: use with caution. Severe impairment: contra-indicated.
Hepatic impairment: Use with caution and avoid in symptomatic or progressive liver disease or hepatic failure.
Oral
Psychoses in Parkinson's disease
Adult: Initially, 12.5 mg once daily at night, increased in steps of 12.5 mg up to 2 times each wk, not >50 mg/day at the end of the 2nd wk. Usual dose: 25-37.5 mg daily. Max: 100 mg daily.
Renal impairment: Mild-moderate renal impairment: use with caution. Severe impairment: contra-indicated.
Hepatic impairment: Use with caution and avoid in symptomatic or progressive liver disease or hepatic failure.
Contraindications
 History of bone marrow disorders including agranulocytosis, circulatory collapse, alcoholic or toxic psychosis, drug intoxication, uncontrolled epilepsy, severe renal, hepatic or cardiac disease; paralytic ileus. Pregnancy and lactation.
Warnings / Precautions
 Leucocyte counts should be monitored regularly and for at least 4 wk after treatment discontinuation. Renal, hepatic or cardiac impairment; prostatic enlargement, narrow-angle glaucoma; elderly; immobilised patients
Adverse Reactions
 Drowsiness, dizziness, headache; nausea, vomiting, constipation; anxiety, confusion, fatigue, transient fever. Rarely, dysphagia, acute pancreatitis, cholestatic jaundice; orthostatic hypotension, tachycardia; seizures; hypersalivation.
Potentially Fatal: Rarely, thromboembolism. Reversible neutropenia which may progress to a potentially fatal agranulocytosis. Fatal myocarditis.
Overdose Reactions
 Altered states of consciousness, including drowsiness, delirium, coma, tachycardia, hypotension, respiratory depression or failure, hypersalivation. Aspiration pneumonia, cardiac arrhythmias, seizures have also been reported. Emesis or gastric lavage, followed by activated charcoal to reduce adsorption. Treatment is symptomatic and supportive with monitoring of cardiac and vital signs. Continue monitoring for several days because of risk of delayed effects. Avoid use of epinephrine and derivatives when treating hypotension and quinidine and procainamide when treating cardiac arrhythmia. Forced diuresis, dialysis, haemoperfusion and exchange transfusion unlikely to be of benefit.
Drug Interactions
 Reduced plasma concentrations with concomitant use of phenytoin. May enhance the central effects of MAOIs.
Potentially Fatal: Concurrent use with bone marrow suppressants e.g. carbamazepine, co-trimoxazole, chloramphenicol, penicillamine, sulfonamides, antineoplastics or pyrazolone analgesics; long-acting depot antipsychotics.
See Below for More clozapine Drug Interactions
Mechanism of Actions
 Clozapine has relatively weak dopamine receptor-blocking activity at D1, D2, D3 and D5 receptors but has high affinity for the D4 receptor. It has also blocking effects on serotonin, α-adrenergic histamine H1 and cholinergic receptors.
Absorption: Absorbed well from the GI tract (oral); peak plasma concentrations after 2.5 hr.
Distribution: Protein-binding: 95%.
Metabolism: Hepatic; N-demethylation and N-oxidation by cytochrome P-450 isoenzyme CYP1A2.
Excretion: Via urine and faeces (as metabolites and trace amounts of unchanged drug); 12 hr (elimination half-life)
Administration
 May be taken with or without food.
Storage Conditions
 Oral: Store below 25°C.
ATC Classification
 N05AH02 - clozapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.
Storage
 Oral: Store below 25°C.
Available As
  • Clozapine 100 mg
  • Clozapine 2 mg
  • Clozapine 200 mg
  • Clozapine 25 mg
  • Clozapine 5 mg
  • Clozapine 50 mg

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