Apo-Clozapine (clozapine) is indicated in the management of symptoms of treatment-resistant schizophrenia. In controlled clinical trials, clozapine was found to improve both positive and negative symptoms.

Due to the significant risk of agranulocytosis and seizure associated with its use, clozapine should be limited to treatment-resistant schizophrenic patients who are non-responsive to, or intolerant of, conventional antipsychotic drugs.

Non-responsiveness is defined as the lack of satisfactory clinical response, despite treatment with appropriate courses of at least 2 marketed chemically-unrelated antipsychotic drugs. Intolerance is defined as the inability to achieve adequate benefit with conventional antipsychotic drugs because of dose-limiting, intolerable adverse effects.

Because of the significant risk of agranulocytosis and seizure, events which both present a continuing risk over time, the extended treatment of patients failing to show an acceptable level of clinical response to clozapine should ordinarily be avoided. In addition, the need for continuing treatment in patients exhibiting beneficial clinical responses should be periodically re-evaluated.

Clozapine can be used only if regular hematological examinations can be guaranteed, as specified under Warnings and Dosage and Administration.

Apo-Clozapine is available only through a distribution system (Apo-Clozapine Risk Management Program) that ensures weekly or every-two-week hematological testing prior to the delivery of the next period's supply of Apo-Clozapine (see Warnings).

This requires:

• registration of the patient, their current location, treating physician, testing laboratory and dispensing pharmacist with the Apo-Clozapine Risk Management Program.
• maintenance of a national Apotex Inc.-specific database that enables the monitoring of the hematological results of all patients on Apo-Clozapine and provides timely feedback (within 24 hours of receipt of the blood test results) to the treating physician and dispensing pharmacist/or pharmacy.
• the ability to identify patients who have been assigned a Non-rechallengeable Status (see Warnings). This requires that Apotex Inc. both provide to, and obtain from all other approved suppliers* of clozapine, the Non-rechallengeable Status/Hematological Status of all patients (see Dosage and Administration). Apotex Inc. must be able to provide this information within 24 hours of receiving a written request.

Physicians should not prescribe Apo-Clozapine until the non-rechallengeable status and the hematological status of the patient has been verified.

For the distribution system to be effective, treating physicians must ensure that the hematological testing is performed at the required frequency (see Warnings) and that the hematological results are sent to Apo-Clozapine Risk Management Program.

Physicians may obtain details on Apo-Clozapine Risk Management Program by calling a toll-free phone number (1-877-276-2569 [1-877-APO-CLOZ]).