WARNING

AGRANULOCYTOSIS; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Agranulocytosis

Clozapine treatment has caused agranulocytosis, defined as an absolute neutrophil count (ANC) less than 500/mm³. Agranulocytosis can lead to serious infection and death. Prior to initiating treatment with VERSACLOZ, obtain a baseline white blood cell count (WBC) and ANC. The ANC must be greater than or equal to 2000/mm³ and the WBC must be greater than or equal to 3500/mm³ for a patient to begin treatment with VERSACLOZ. During treatment, patients must have regular monitoring of ANC and WBC. Discontinue VERSACLOZ and do not rechallenge if the ANC is less than 1000/mm³ or the WBC is less than 2000/mm³. Advise patients to immediately report symptoms consistent with agranulocytosis or infection (e.g., fever, weakness, lethargy, or sore throat). [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Because of the risk of agranulocytosis, VERSACLOZ is available only through a restricted program called the VERSACLOZ Patient Registry. Under the VERSACLOZ Patient Registry, prescribers, patients, and pharmacies must enroll in the program [see WARNINGS AND PRECAUTIONS].

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. 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) [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

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 [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Myocarditis and Cardiomyopathy

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 or cardiomyopathy if chest pain, tachycardia, palpitations, dyspnea, fever, flu-like symptoms, hypotension, or ECG changes occur [see WARNINGS AND PRECAUTIONS].

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 [see WARNINGS AND PRECAUTIONS].