Health Canada releases important information on the dispensation of CLOZAPINE products in Canada - For Health Professionals

Health Canada releases important information on the dispensation of CLOZAPINE products in Canada

June 23, 2004

Subject: Monitoring of patients taking clozapine in Canada

Dear Health Care Professional,

The Marketed Health Products Directorate (MHPD) and the Therapeutic Products Directorate (TPD) would like to draw your attention to important upcoming revisions to the Product Monographs of all clozapine products marketed in Canada. These revisions will strengthen the labelling and address ongoing issues around patient consent for the sharing of information between registries. As you know, monitoring of patients with the use of registries is the risk mitigation strategy in place to address the known risk of agranulocytosis.

Revisions to clozapine Product Monographs will emphasize the following:

1. the switching of a patient from one brand of clozapine to another must not be done by a pharmacist unless he/she obtains a new, registry-specific patient registration form filled out by the prescribing physician.
2. the physician has to inform his/her patient about the potential sharing of information between clozapine registries and document if there is consent from the patient to allow it, in order to ensure the safe use and continuous monitoring of patients taking clozapine.
3. the responsibility of physicians concerning the sending of the mandatory laboratory results (white blood cell counts and differential) to the appropriate registry will be limited to informing the laboratory where the patient's haematological results have to be sent.
4. weekly monitoring of neutrophils and white cell counts for four weeks at the end of the treatment is necessary only in case of cessation of all clozapine treatment.

Due to a significant risk of agranulocytosis, patients on clozapine and their treating physicians and dispensing pharmacists have to be enrolled in registries, which are currently specific to each market authorization holder. Patients must undergo regular haematological tests to monitor their total white blood-cell and absolute neutrophil counts. Between 1991 and 2003, clozapine was distributed by a single manufacturer, and patients were monitored by this manufacturer's specific registry. The introduction of generic clozapine in the last year has led to the establishment of other registries.

After consultations with representatives from market authorization holders, the Canadian Psychiatric Association (CPA), the Schizophrenia Society of Canada and the National Association of Pharmacy Regulatory Authorities (NAPRA), Health Canada is taking the following steps to ensure the safe use and continuous monitoring of patients taking clozapine in Canada:

• inclusion of a statement in the registry-specific Patient Registration Form signed by the treating physician (see proposed text in attachment 1), certifying that the patient has been informed of the necessary sharing of information between clozapine registries to enable continuous monitoring and safe use of the medication. The inclusion of this text in the Patient Registration Form is necessary to overcome ongoing problems with the exchange of information between registries, caused in part by some potential implications of the "Personal Information Protection and Electronic Documents Act" (PIPEDA), the federal legislation protecting personal information in the private sector, including health information. As a preventive measure and to avoid any confusion, physicians may also ask patients already on clozapine to fill out the updated Patient Registration Form
• A "Questions and Answers" patient information leaflet, prepared in collaboration with the Schizophrenia Society of Canada, is also provided (see attachment 2), to help physicians to document the actual consent from the patient on information exchange between registries
• Appropriate revision of clozapine Product Monographs to reflect the above

Any questions related to a clozapine product or a registry should be directed to the company concerned. Any further questions on clozapine Products Monographs' updates should be adressed to the Therapeutic Products Directorate (TPD), by phone: (613) 957-0368, by fax: (613) 952-7756 or by email: TPD-General-DPT-Général@hc-sc.gc.ca. Any further questions related to this letter should be adressed to the Marketed Health Products Directorate (MHPD): (613) 946-5140, by fax: (613) 946-6011 or by email: mhpd_dpsc@hc-sc.gc.ca.

The implementation of these steps will permit the achievement of a more efficient network of independent registries, and therefore improve the continuity of care of patients treated with clozapine.

We thank you in advance for your collaboration in the implementation of these changes.

original signed by

Christopher Turner, MD FRCPC

Director General

Marketed Health Products Directorate

original signed by

Robert Peterson, MD MPH PhD

Director General

Therapeutic Products Directorate

Attachment 1

Statement by Treating Physician

[Note: Statement proposed to be included in Patient Registration Form]

I, the treating physician, will ensure that blood testing (white blood cell count and differential) for this patient (identified below) as required by the clozapine Product Monographs is performed at the specified frequency. I understand that no pharmacy will dispense any brand of clozapine to my patient without my prior knowledge and permission regarding which brand is being dispensed. In this way I will be able to inform the laboratory to send my patient's results to the appropriate manufacturer's clozapine database. I will not prescribe clozapine until the non-rechallengeable status of this patient has been verified.

I have informed the patient and he/she has not objected to the release of relevant safety information held within a clozapine database to any other clozapine database of an approved manufacturer of clozapine in Canada, if needed for the safe utilization of this medication and/or for the continuous monitoring of the patient. The information which may be released includes, the non-rechallengeable/haematological status of the patient, white blood cell counts and absolute neutrophils counts, dates and other information as may be relevant to the safe treatment of the patient with clozapine.

Name of treating physician:

Physician license number:

Signature of treating physician:

Date: (DD/MM/YYYY)

Patient Initials:

Date of Birth (DD/MM/YYYY):

Gender: M / F

Province / Health Card Number:

Attachment 2

Q and As Regarding Patient Consent for information sharing

1. Why does my blood need to be monitored if I am taking clozapine?

Clozapine has been associated with a serious condition that reduces white blood cell counts (agranulocytosis). Due to the risk of developing this condition, regular blood testing of white blood cell counts must take place for individuals on clozapine, to ensure that the white blood cell counts remains within the normal range.

2. Why does my doctor need my consent?

The medication you are taking, clozapine, is produced by several different suppliers. Each supplier has a different monitoring system to ensure patient safety. Should your doctor and/or pharmacist (with the approval of your doctor) change the brand of clozapine you are taking, you will be transferred to a different monitoring system. If this happens, it is very important that your new supplier is able to access your past white blood cell counts results in order to help your doctor ensure that you are properly monitored.

It is also important to check with all registries at the start of the treatment that you have not experienced in the past a decrease of your white blood cell count with clozapine. Your consent is needed to allow this verification and sharing of information to take place.

3. Why is personal information such as my initials, birth date, gender and health card number being collected and used for identification purposes?

This information will be collected and used for several reasons. Since this information is specific to you, it helps to ensure that your test results are not mixed up with those of another person on the same medication. Using this information also avoids the need to use your full name and therefore protects your privacy.

4. Can my personal information be used for other purposes?

No. Your information will only be used to ensure that you are properly monitored while using any brand of clozapine.

5. Where can I find information on the protection of health related personal information in the private sector?

Information on this topic can be found on the web site of Industry Canada.

The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse reaction reporting programmes. Any occurrences of serious and/or unexpected adverse reactions in patients receiving clozapine should be reported to Health Canada at the following address:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

HEALTH CANADA

Address Locator: 0701C

OTTAWA, Ontario, K1A 0K9

Tel: (613) 957-0337 or Fax: (613) 957-0335

To report an Adverse Reaction, consumers and health professionals may call toll free:

Tel: 866 234-2345

Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

For other inquiries: please refer to contact information.

The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.