Clozapine (Clozaril) is an "atypical" antipsychotic medication in that it is preferentially more active at limbic than at striatal dopamine receptors and causes few or no EPS. Unfortunately, it may produce agranulocytosis, so its use is reserved for patients with schizophrenia unresponsive to standard agents and for those suffering from severe EPS or tardive dyskinesia with the standard agents. Use of clozapine requires weekly complete blood counts (CBC) the first 6 months of use and then every 2 weeks after that. Any white blood cell count less than 3500 requires closer monitoring, whereas a white blood cell count less than 2000 or absolute granulocyte count less than 1000 mandates immediate discontinuation of the drug and consultation with a hematologist. Fever may be a side effect during the first few weeks of therapy and should prompt an immediate CBC. If the CBC is normal, the fever will typically reverse. Clozapine is strongly sedating, strongly anticholinergic, and has considerable hypotensive effects. It also poses a substantial risk for inducing seizures, particularly when higher doses are used. Respiratory depression and arrest have been reported rarely, and there is a suggestion that coprescription of a benzodiazepine may increase the risk for this side effect.
Commonly reported features of overdose include altered sensorium (drowsiness, delirium, and coma), tachycardia, hypotension, respiratory depression and failure, hypersalivation, and seizures. Management, in addition to administration of activated charcoal, is symptomatic and supportive. Epinephrine and its derivatives should be avoided, as should antidysrythymics such as procainamide and quinidine. Close surveillance, including cardiac and vital sign monitoring, should continue for several days because of risk of delayed toxic effects. Fatal overdosages have been reported, usually at dosages over 2500 mg.
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