Clozapine

May be taken with or without food.

History of toxic or idiosyncratic agranulocytosis/granulocytopenia, neutropenia, impaired bone marrow function, uncontrolled epilepsy, circulatory collapse, CNS depression of any cause, severe cardiac disorder, circulatory collapse, paralytic ileus, alcoholic or toxic psychosis, drug intoxication. Severe renal and hepatic (including active or progressive liver disease, hepatic failure) impairment. Concomitant use with long-acting depot antipsychotics, alcohol.

Patient with CV or cerebrovascular disease or conditions predisposing to hypotension, history of or risk factors for seizure, risk or history of QT prolongation, DM, BPH, urinary retention, xerostomia, decreased gastrointestinal motility, visual problems. Smokers. CYP2D6 poor metabolisers. Patients taking strong CYP2D6 inhibitors. Avoid abrupt withdrawal. Renal and hepatic impairment. Elderly (not indicated for use in dementia-related psychosis). Pregnancy and lactation. Patient Counselling This drug may cause seizures, somnolence and motor or sensory instability, if affected, do not drive or operate machinery. Monitoring Parameters Obtain baseline CBC, including ANC (must be ≥1,500/mm³ prior to initiation of treatment to general population and ≥1,000/mm³ in patients with benign ethnic neutropenia prior to initiation of treatment); serum cholesterol, triglycerides, LDL and HDL concentrations; ECG, blood pressure. Monitor for signs and symptoms of neutropenia or infection (e.g. fever, weakness, lethargy, sore throat); myocarditis (e.g. chest pain, tachycardia, palpitations, dyspnoea); bowel function, constipation, mental changes, fever, muscle rigidity.

Significant: Orthostatic hypotension, bradycardia, syncope, seizures, decreased gastrointestinal motility, urinary retention, xerostomia, visual problems, CNS depression, dyslipidaemia, eosinophilia, oesophageal dysmotility/aspiration, extrapyramidal symptoms, risk of fall, fever, hyperglycaemia, QT prolongation, sialorrhoea and drooling, suicidal ideation, temperature regulation disturbance, deep vein thrombosis, pulmonary embolism, weight gain. Cardiac disorders:Tachycardia. Gastrointestinal disorders: Constipation, nausea, vomiting, dyspepsia. Nervous system disorders: Dizziness, insomnia, vertigo, headache. Vascular disorders: Hypertension.
Potentially Fatal: Severe agranulocytosis/neutropenia, myocarditis and cardiomyopathy, hepatotoxicity including hepatic failure, hepatic necrosis and hepatitis, torsade de pointes, cardiac arrest, neuroleptic malignant syndrome, respiratory depression or failure, paralytic ileus, intestinal obstruction, faecal impaction.

Enhances the CNS effects of narcotics, antihistamines and benzodiazepines. May reduce therapeutic effect of norepinephrine. Increased plasma level with CYP1A2 inhibitors (e.g. ciprofloxacin, fluvoxamine, enoxacin, oral contraceptives, caffeine). Decreased plasma level with CYP1A2 inducers. Increased risk of neuroleptic malignant syndrome with lithium. Risk of seizures with valproic acid.

Antipsychotics

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