Important safety information regarding tamoxifen and incidence of uterine malignancies, stroke and pulmonary embolism

Information on tamoxifen’s safety, including the likelihood of uterine cancer, stroke, and pulmonary embolism.

Date: 2002-02-28

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As a service to healthcare professionals, consumers, and other interested parties, the Marketed Health Products Directorate (MHPD), Therapeutic Products Directorate (TPD), and Biologics and Genetic Therapies Directorate (BGTD) publish safety alerts, public health advisories, press releases, and other notices from industry. While MHPD, TPD, and BGTD approve therapeutic items, they do not support the firm or the product in any way. Your health care provider should be consulted with any inquiries you may have about product information.

Information on tamoxifen’s safety, including the likelihood of uterine cancer, stroke, and pulmonary embolism.

7 November 2002

To: Oncologists, Hospital Chief Medical Staff

In addition to posting this NOTICE in your institution, please forward it to the relevant Departments (Medical Directors; Director, Department of Family Medicine; Director, Department of Pharmacy; Director, Department of Gynecology; Director, Department of Oncology).

Using tamoxifen with the risk of uterine cancer, stroke, and pulmonary embolism has critical safety information, which Health Canada would like to bring to your notice. The NSABP P-1 study (National Surgical Adjuvant Breast and Bowel Project Breast Cancer Preventative) involved women receiving tamoxifen in a prevention context who were at high risk for breast cancer or who had ductal carcinoma in situ (DCIS). It is stressed that the use of tamoxifen for preventative purposes is not a Canadian approved indication.

The advantages of using tamoxifen have been determined to outweigh the potential risks for the indications currently approved in Canada, “treatment of breast cancer in estrogen receptor positive tumors” (Product Monograph Novaldex-D (tamoxifen citrate), AstraZeneca Canada Inc., date of revision May 2, 2002). Regardless of the manufacturer, this information is applicable to all tamoxifen-containing drugs.

In the patient group of the NSABP P-1 study, tamoxifen medication was linked to higher rates of uterine malignancies, stroke, and pulmonary embolism than placebo. Endometrial adenocarcinomas and uterine sarcomas were the two types of uterine malignancies, and the incidence rates per 1,000 women-years were 2.20 for tamoxifen and 0.71 for a placebo, respectively. Tamoxifen had a stroke incidence rate per 1,000 women-years of 1.43 compared to a placebo’s 1.00. Tamoxifen had a 0.75 pulmonary embolism incidence rate per 1,000 women-years compared to a 0.25 incidence rate for placebo. The NSABP P-1 study’s median follow-up duration is now 6.9 years1.

It is usually assumed that reporting rates based on spontaneously reported post-marketing adverse events understate the hazards connected to pharmacological therapy.

The active involvement of healthcare professionals in programs for reporting adverse drug reactions is essential for the discovery, categorization, and management of drug-related adverse events. The Marketed Health Products Directorate at the following address is where healthcare practitioners are urged to report any suspected adverse effects in patients receiving tamoxifen:

You can also report any alleged pharmacological side effects to:

Program for Monitoring Adverse Drug Reactions in Canada (CADRMP)

Directorate of Marketed Health Products

HEC Canada

Locator for Address: 0201C2

Ontario, K1A 1B9 OTTAWA

Tel: (613) 957-0337 or

Fax: (613) 957-0335

Free phone number for patients and medical professionals: Tel: 866 234-2345,

Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

The ADR Reporting Form and the ADR Guidelines can be found in The Canadian Compendium of Pharmaceuticals and Specialties or on the TPD website.

Your professional commitment in this area plays a significant part in ensuring the health of your patients by helping to identify early warning signs and use medication wisely.

In the interest of patient safety, Health Canada requests that you distribute these recommendations to your staff or membership and encourage their implementation.

Reference:

Tamoxifen for prevention of breast cancer: a report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study, Fisher B, Costantino IP, Wickerham DL et al. pp. 1371 in J. Natl. Cancer Inst. 90 (1998).