Clozaril

Treatment-resistant schizophrenia ie, non-responsive to or intolerant of classic antipsychotics. Reduce risk of recurrent suicidal behaviour in patients w/ schizophrenia or schizoaffective disorders.

12.5 mg (½ of 25 mg tab) once or bd on 1st day, followed by 25 or 50 mg on 2nd day, may be increased in 25- or 5-mg increments to daily dose: 300 mg w/in 2-3 wk. Thereafter, may be further increased in 50-100 mg increments at half or wkly intervals. Max: 900 mg daily. Heart disease or mild to moderate renal insufficiency Initially 12.5 on 1st day, increase slowly & in small increments. Elderly ≥60 yr Initially 12.5 mg once daily on 1st day w/ subsequent dose increments restricted to 25 mg daily.

May be taken with or without food.

Hypersensitivity. Patients unable to undergo regular blood tests; history of toxic or idiosyncratic granulocytopenia/agranulocytosis (except due to previous chemotherapy); impaired bone marrow function; uncontrolled epilepsy; alcoholic & other toxic psychoses, drug intoxication, comatose conditions; circulatory collapse; CNS depression; paralytic ileus. severe renal or cardiac disorders; active liver disease associated w/ nausea, anorexia or jaundice; progressive liver disease, hepatic failure.

Discontinue use if WBC count <3,000/mm³ or ANC <1,500/mm³ during 1st 18 wk, or if WBC count <2,500/mm³ or ANC <1,000/mm³ after 1st 18 wk of therapy; eosinophil count >300/mm³, platelet count <50,000/mm³; myocarditis & NMS are confirmed. History of primary bone marrow disorders; low WBC counts due to benign ethnic neutropenia. CV disorders; orthostatic hypotension; mitral valve incompetence due to cardiomyopathy; MI; family history of QT prolongation; risk factors for stroke; thromboembolism; metabolic changes; hyperglycemia & DM; wt gain; history of seizures; anticholinergic effects, prostatic enlargement, narrow-angle glaucoma. Rule out underlying infections in patients w/ fever. Avoid immobilization of patients. Perform WBC & neutrophil counts wkly during 1st 18 wk & at least every 4 wk during treatment then monitor throughout & for 4 wk after last dose. Immediately perform differential blood count if signs & symptoms of infection occurs. Perform clinical monitoring including baseline & periodic follow-up of lipid evaluations. Gradually w/draw over 1-2 wk period. Not to be used concurrently w/ drugs substantially depressing bone marrow function. Avoid concomitant use of long-acting depot antipsychotics. Concomitant use w/ medicines increasing QTc interval. May affect ability to drive or use machines. Hepatic & renal impairment. Women of childbearing potential should use effective contraception during treatment. Pregnancy. Not to be used during lactation. Childn & adolescents. Elderly ≥60 yr w/ dementia-related psychosis.

Drowsiness/sedation, dizziness, restless leg syndrome; tachycardia; constipation, hypersalivation. Leukopenia/decreased WBC/neutropenia, eosinophilia, leucocytosis; wt gain; dysarthria; seizures/convulsions/myoclonic jerks, extrapyramidal symptoms, akathisia, tremor, rigidity, headache; blurred vision; ECG changes; syncope, postural hypotension, HTN; nausea, vomiting, dry mouth; elevated liver enzymes; urinary retention & incontinence; benign hyperthermia, disturbances in sweating/temp regulation, fatigue.

Increased risk of circulatory collapse w/ benzodiazepine or any other psychotropic agent. Increased risk of NMS w/ lithium or other CNS-active agents. Increased onset of seizures w/ valproic acid. Enhanced central effects of alcohol, MAOIs, CNS depressants eg, narcotics, antihistamines. Additive effects w/ substances possessing anticholinergic, hypotensive or resp depressant effects. Reduced BP-increasing effect of norepinephrine or other predominantly α-adrenergic agents. Reversed pressor effect of epinephrine. Decreased plasma levels w/ CYP450 inducers eg, carbamazepine, phenytoin, rifampicin; omeprazole, tobacco smoke. Increased plasma levels w/ CYP450 inhibitors eg, cimetidine, erythromycin, fluvoxamine, perazine, ciprofloxacin, OCs; SSRIs eg, paroxetine, sertraline, fluoxetine, citalopram; azole antimycotics, PIs. Increased/decreased plasma conc w/ caffeine. Not to be used concurrently w/ medicines substantially depressing bone marrow function. Caution w/ medicines increasing QTc interval or causing electrolyte imbalance; CYP1A2 & 3A4 inhibitors or inducers.

Antipsychotics

N05AH02 - clozapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.

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