WARNING:
SEVERE NEUTROPENIA;
ORTHOSTATIC HYPOTENSION,
BRADYCARDIA, AND
SYNCOPE; SEIZURE;
MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY;
INCREASED MORTALITY IN
ELDERLY PATIENTS WITH
DEMENTIA-RELATED
PSYCHOSIS
Severe Neutropenia
VERSACLOZ has caused severe neutropenia which is associated with an increased risk of serious and potentially fatal infections.
Prior to initiating VERSACLOZ treatment, obtain baseline ANC(s). VERSACLOZ 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 VERSACLOZ treatment.
Consider a hematology consultation before initiating VERSACLOZ or during VERSACLOZ treatment.
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 to minimize risk. Use VERSACLOZ cautiously in patients
with cardiovascular or 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.