Significant risk of agranulocytosis, potentially life-threatening. May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention; use with caution in decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems). Myocarditis, pericarditis, pericardial effusion, cardiomyopathy, and heart failure described. May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Atypical antipsychotics have been associated with development of hyperglycemia (may be associated with ketoacidosis, hyperosmolar coma, or death). Use with caution in diabetes or other disorders of glucose regulation. Use may be associated with neuroleptic malignant syndrome. May cause orthostatic hypotension (with or without syncope) and tachycardia. May be moderate to highly sedating. Seizures have been associated with clozapine use in a dose-dependent manner. Elderly patients may be at increased risk of seizures. The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder. Impaired core body temperature regulation may occur. Rare cases of thromboembolism, including pulmonary embolism and stroke resulting in fatalities, have been associated with clozapine in cardiovascular disease. Significant weight gain observed with antipsychotic therapy. Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo. Clozapine is not approved for dementia-related psychosis. Use with caution in narrow-angle glaucoma (may be exacerbated by cholinergic blockade). Use with caution in hepatic disease or impairment (hepatitis reported as a consequence of therapy). Use with caution in myasthenia gravis (may be exacerbated by cholinergic blockade). Use with caution in renal impairment. Concurrent use with benzodiazepines may increase the risk of severe cardiopulmonary reactions. Medication should not be stopped abruptly. Cigarette smoking may enhance the metabolism of clozapine.