WARNING:
SEVERE NEUTROPENIA;
ORTHOSTATIC HYPOTENSION,
BRADYCARDIA, AND
SYNCOPE; SEIZURE;
MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY;
INCREASED MORTALITY IN
ELDERLY PATIENTS WITH
DEMENTIA-RELATED
PSYCHOSIS
Severe Neutropenia
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
VERSACLOZ 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,
VERSACLOZ is available only
through a restricted program
under a Risk Evaluation
Mitigation Strategy (REMS)
called the Clozapine REMS
Program.
Orthostatic Hypotension,
Bradycardia, Syncope
Orthostatic hypotension,
bradycardia, syncope, and
cardiac arrest have occurred
with clozapine 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 Versacloz. Initiate
treatment at 12.5 mg once or
twice daily; titrate slowly; and
use divided dosages. Use
VERSACLOZ cautiously in
patients with
cardiovascular/cerebrovascular
disease or conditions
predisposing to hypotension
(e.g., dehydration, use of
antihypertensive medications).
Seizures
Seizures have occurred with
clozapine treatment. The risk is
dose-related. Initiate treatment
at 12.5 mg, titrate gradually, and
use divided dosing. Use caution
when administering
VERSACLOZ 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 loss of consciousness
could cause serious risk to
themselves or others.
Myocarditis, Pericarditis, Cardiomyopathy and Mitral Valve Incompetence
Fatal myocarditis and
cardiomyopathy have occurred
with clozapine treatment.
Discontinue VERSACLOZ and
obtain a cardiac evaluation
upon suspicion of these
reactions. Generally, patients
with VERSACLOZ-related
myocarditis or cardiomyopathy
should not be rechallenged with
VERSACLOZ. Consider the possibility of myocarditis, pericarditis, or cardiomyopathy if chest pain,
tachycardia, palpitations,
dyspnea, fever, flu-like
symptoms, hypotension, or ECG
changes occur.
Increased Mortality in Elderly
Patients with Dementia-Related
Psychosis
Elderly patients with
dementia-related psychosis
treated with antipsychotic drugs
are at an increased risk of
death. VERSACLOZ is not
approved for use in patients
with dementia-related
psychosis.