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Treatment resistant schizophrenia. To reduce risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorders.

Dibenzodiazepine; Antipsychotic

Clozapine is classified as an \'atypical\' antipsychotic drug because of its profile of binding to dopamine receptors and its effects on various dopamine-mediated behaviors differ from those exhibited by other typical antipsychotic drug products. In particular, although Clozapine does interfere with the binding of dopamine at D1, D2, D3 and D5 receptors, and has a high affinity for the D4 receptor. This evidence, consistent with the view that Clozapine is preferentially more active at limbic than at striatal dopamine receptors. This may explain the relative freedom of Clozapine from extrapyramidal side effects. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors.

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 w/in 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. 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.

Olanzapine may antagonize the effects of levodopa and dopamine agonists. Drugs that induce CYP1A2 or glucoronyl transferase enzymes e.g, Omeprazole and Rifampicin, may increase Olanzapine clearance. Inhibitors of CYP1A2 may potentially inhibit Olanzapine elimination. Carbamazepine may increase the clearance of Olanzapine. Concomitant administration of activated charcoal reduces the oral bioavailability of Olanzapine by 50-60%. Caution should be taken when Olanzapine is administered with centrally acting drugs and alcohol.

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 & lactation. Leucocyte counts should be monitored regularly & for at least 4 wk after treatment discontinuation. Renal, hepatic or cardiac impairment; prostatic enlargement, narrow-angle glaucoma; elderly; irnmobilised patients

Drowsiness, dizziness, headache; nausea, vomiting, constipation; anxiety, confusion, fatigue, transient fever. Rarely, dysphagia, acute pancreatitis, cholestatic jaundice; orthostatic hypotension, tachycardia; seizures; hypersalivation. Rarely, thromboembolism. Reversible neutropenia which may progress to a potentially fatal agrariulocytosis. Fatal myocarditis.

increased chances of pregnancy both desired and unwanted in woman taking clozapine. Sufficient data are not available to psychiatrists to guide the management of such cases. The following case adds to the existing data on the use of clozapine during pregnancy. Since clozapine is present in the maternal milk, breast feeding should be avoided.

The most commonly reported signs and symptoms associated with Clozapine overdose are: altered states of consciousness, including drowsiness, delirium and coma; tachycardia; hypotension; respiratory depression or failure; hypersalivation. Aspiration pneumonia and cardiac arrhythmias have also been reported. Seizures have occurred in a minority of reported cases. Fatal overdoses have been reported with Clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g. Management of Overdose: Should be established and maintained an airway; should be ensured adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.In managing overdosage, the physician should consider the possibility of multiple drug involvement.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

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