Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) –
BOXED WARNING - updated/truncated to show changes
WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
- Clozapine treatment has caused severe neutropenia, defined as an absolute neutrophil count (ANC) less than 500/µL. Severe neutropenia can lead to serious infection and death. Prior to initiating treatment with Fazaclo a baseline ANC must be at least 1500/µL for the general population; and must be at least 1000/µL for patients with documented Benign Ethnic Neutropenia (BEN). During treatment, patients must have regular ANC monitoring. Advise patients to immediately report symptoms consistent with severe neutropenia or infection (e.g., fever, weakness, lethargy, or sore throat). Because of the risk of severe neutropenia, Fazaclo is available only through a restricted program under a Risk Evaluation Mitigation Strategy (REMS) called the Clozapine REMS Program…
- Fazaclo is contraindicated in patients with a history of serious hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of Fazaclo
WARNINGS AND PRECAUTIONS
- * update the neutropenia monitoring algorithms and associated Fazaclo (clozapine) treatment recommendations; and to accommodate for Fazaclo (clozapine) treatment for patients with benign ethnic neutropenia
Clozapine REMS Program
- For hospice patients (i.e., terminally ill patients with an estimated life expectancy of six months or less), the prescriber may reduce the ANC monitoring frequency to once every 6 months, after a discussion with the patient and his/her caregiver. Individual treatment decisions should weigh the importance of monitoring ANC in the context of the need to control psychiatric symptoms and the patient’s terminal illness.
QT Interval Prolongation
- QT prolongation is associated with an increased risk for life-threatening ventricular arrhythmias including Torsades de Pointes. Treatment with FazaClo (clozapine, USP) has been associated with QT prolongation as well as ventricular arrthymia, Torsades de Pointes, cardiac arrest, and sudden death. Caution should be exercised when .....
Drug Interactions and Pharmacodynamic-Related Interactions:
- Treatment with FazaClo® (clozapine, USP) , has been associated with QT interval prolongation and fatal arrhythmia......
- Use caution when prescribing FazaClo......
Postmarketing Clinical Experience:
- Ventricular tachycardia, cardiac arrest, QT prolongation, and Torsades de Pointes.
Cerebrovascular adverse events
- An increased risk of cerebrovascular adverse events has been seen in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Clozaril should be used with caution in patients with risk factors for stroke.
Postmarketing Clinical Experience
- Central Nervous System: obsessive compulsive symptoms
- Metabolic and Nutritional Disorders: new onset diabetes
- Respiratory System: pneumonia and lower respiratory tract infection which may be fatal