Clozapine (4 brand names, 3 dosage forms, 1 route)
Available dosage forms: TABLET, TABLET, ORALLY DISINTEGRATING, SUSPENSION.
Routes of administration: ORAL.
Brand Names
- CLOZAPINE
- CLOZARIL
- FAZACLO ODT
- VERSACLOZ
Boxed Warning
Severe Neutropenia Clozapine tablets have caused severe neutropenia which is associated with an increased risk of serious and potentially fatal infections. Prior to initiating clozapine tablets treatment, obtain baseline ANC(s). Clozapine tablets initiation is not recommended in patients with a baseline ANC less than 1500/μL (less than 1000/μL for those with Benign Ethnic Neutropenia (also known as Duffy-null associated neutrophil count)). See recommendations for dosage modifications based on ANC levels during clozapine tablets treatment [see Dosage and Administration (2.3, 2.4)]. Consider a hematology consultation before initiating clozapine tablets or during clozapine tablets treatment [see Warnings and Precautions (5.1)]. Orthostatic Hypotension, Bradycardia, Syncope Orthostatic hypotension, bradycardia, syncope, and cardiac arrest have occurred with clozapine tablets treatment. The risk is highest during the initial titration period, particularly with rapid dose escalation. These reactions can occur with the first dose, with doses as low as 12.5 mg per day, or when restarting patients who have had even a brief interruption in treatment with clozapine tablets. Initiate treatment at 12.5 mg once or twice daily; titrate slowly; and use divided dosages to minimize risk. Use clozapine tablets cautiously in patients with cardiovascular or cerebrovascular disease or conditions predisposing to hypotension (e.g., dehydration, use of antihypertensive medications) [see Dosage and Administration (2.2, 2.6) , Warnings and Precautions (5.2) ]. Seizures Seizures have occurred with clozapine tablets treatment. The risk is dose-related. Initiate treatment at 12.5 mg, titrate gradually, and use divided dosing. Use caution when administering clozapine tablets to patients with a history of seizures or other predisposing risk factors for seizure (CNS pathology, medications that lower the seizure threshold, alcohol abuse). Caution patients about engaging in any activity where sudden
Contraindications
Clozapine tablets are contraindicated in patients with a history of hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson syndrome) or any other component of clozapine tablets [see Adverse Reactions (6.2)].
Adverse Reactions
The following adverse reactions are discussed in more detail in other sections of the labeling: •Severe Neutropenia [see Warnings and Precautions (5.1)] •Orthostatic Hypotension, Bradycardia, and Syncope [see Warnings and Precautions (5.2)] •Falls [see Warnings and Precautions (5.3)] •Seizures [see Warnings and Precautions (5.4)] •Myocarditis, Pericarditis, Cardiomyopathy, and Mitral Valve Incompetence [see Warnings and Precautions (5.5)] •Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.6)] •Gastrointestinal Hypomotility with Severe Complications [see Warnings and Precautions (5.7)] •Eosinophilia [see Warnings and Precautions (5.8)] •QT Interval Prolongation [see Warnings and Precautions (5.9)] •Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain) [see Warnings and Precautions (5.10)] •Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.11)] •Hepatotoxicity [see Warnings and Precautions (5.12)] •Fever [see Warnings and Precautions (5.13)] •Pulmonary Embolism [see Warnings and Precautions (5.14)] •Anticholinergic Toxicity [see Warnings and Precautions (5.15)] •Interference with Cognitive and Motor Performance [see Warnings and Precautions (5.16)] •Tardive Dyskinesia [see Warnings and Precautions (5.17)] •Cerebrovascular Adverse Reactions [see Warnings and Precautions (5.18)] •Recurrence of Psychosis and Cholinergic Rebound after Abrupt Discontinuation [see Warnings and Precautions (5.19)]
Mechanism of Action
The mechanism of action of clozapine is unknown. However, it has been proposed that the therapeutic efficacy of clozapine in schizophrenia is mediated through antagonism of the dopamine type 2 (D2) and the serotonin type 2A (5-HT2A) receptors. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and other dopaminergic and serotonergic receptors.