CLOZAPINE- clozapine tablet, orally disintegrating
Mylan Pharmaceuticals Inc.
WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS 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/?L. Severe neutropenia can lead to serious infection and death. Prior to initiating treatment with clozapine orally disintegrating tablets, a baseline ANC must be at least 1500/?L for the general population; and must be at least 1000/?L 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) [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)].
Because of the risk of severe neutropenia, clozapine orally disintegrating tablets are available only through a restricted program under a Risk Evaluation Mitigation Strategy (REMS) called the Clozapine REMS Program [see Warnings and Precautions (5.2)].
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 clozapine orally disintegrating 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 (2.3, 2.6) and Warnings and Precautions (5.3)].
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 clozapine orally disintegrating 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 loss of consciousness could cause serious risk to themselves or others [see Dosage and Administration (2.3) and Warnings and Precautions (5.5)].
Myocarditis and Cardiomyopathy
Fatal myocarditis and cardiomyopathy have occurred with clozapine treatment. Discontinue clozapine orally disintegrating tablets and obtain a cardiac evaluation upon suspicion of these reactions. Generally, patients with clozapine orally disintegrating tablets-related myocarditis or cardiomyopathy should not be rechallenged with clozapine orally disintegrating tablets. 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 (5.6)].
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. Clozapine orally disintegrating tablets are not approved for use in patients with dementia-related psychosis [see Warnings and Precautions (5.7) ].
1 INDICATIONS AND USAGE
1.1 Treatment-Resistant Schizophrenia
Clozapine orally disintegrating tablets are indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. Because of the risks of severe neutropenia and of seizure associated with its use, clozapine orally disintegrating tablets should be used only in patients who have failed to respond adequately to standard antipsychotic treatment [see Warnings and Precautions (5.1, 5.5)].
The effectiveness of clozapine in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active-controlled study comparing clozapine and chlorpromazine in patients who had failed other antipsychotics [see Clinical Studies (14.1)].
