IMURAN (azathioprine) or PURINETHOL (mercaptopurine) - Association with a Type of Blood Cancer - Hepatosplenic T-Cell Lymphoma - For Health Professionals

Starting date:

March 26, 2014

Posting date:

March 26, 2014

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

Important Safety Information

Audience:

Healthcare Professionals

Identification number:

RA-38691

This is duplicated text of a letter from Triton Pharma Inc. and Teva Canada Ltd. Contact the companies for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on IMURAN and PURINETHOL

March 26, 2014

Dear Health Care Professional,

Subject: Association of IMURAN^® (azathioprine) or PURINETHOL® (mercaptopurine) with Hepatosplenic T-Cell Lymphoma (HSTCL)

Triton Pharma Inc. and Teva Canada Ltd., in consultation with Health Canada, would like to inform you of the association between the use of purine antagonists IMURAN^® (azathioprine) or PURINETHOL^® (mercaptopurine) and the development of hepatosplenic T-cell lymphoma (HSTCL), a rare¹ but serious cancer, mostly in patients where it is used for inflammatory bowel disease (IBD). IMURAN^® (azathioprine) is a drug used to treat adult rheumatoid arthritis and help prevent kidney transplant rejection. PURINETHOL^® (mercaptopurine) is a drug approved to treat cancer (leukemias).

• Cases of Hepatosplenic T-cell Lymphoma (including fatalities) have been reported in IBD patients treated with IMURAN^® (azathioprine) or PURINETHOL^® (mercaptopurine) monotherapy.
• IMURAN^® (azathioprine) and PURINETHOL^® (mercaptopurine) labels have been updated for HSTCL and physicians should discuss the currently available information regarding risks and benefits of these treatments with their patients.
• IMURAN^® (azathioprine) or PURINETHOL^® (mercaptopurine) monotherapies are not authorized by Health Canada for the treatment of Inflammatory Bowel Disease (IBD).

Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive and often fatal cancer. Cases of HSTCL (including fatalities) have been reported with IMURAN^® (azathioprine) or PURINETHOL^® (mercaptopurine), mostly in patients where it is used for inflammatory bowel disease (IBD).  In Canada, since time of marketing to November 30^th, 2013, 2 cases (1 fatal) of HSTCL with mercaptopurine and 4 cases of HSTCL with azathioprine (3 fatal) have been reported to Health Canada. 

The complete prescribing and adverse event information for IMURAN^® can be found in the approved Product Monograph² which is available on the Health Canada website and on the Triton Pharma Inc. website.

The complete prescribing and adverse event information for PURINETHOL^® can be found in the approved Product Monograph³ which is available on the Health Canada website and on the Teva Canada Ltd. website.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of HSTCL or other serious or unexpected adverse reactions in patients receiving IMURAN^® or PURINETHOL^® should be reported to Triton Pharma Inc. or Teva Canada Ltd., respectively, or Health Canada.

Triton Pharma Inc.

665 Millway Avenue

Concord, Ontario L4K 3T8

Telephone: 1-866-429-9707

E-mail: drug.safety.triton@paladinlabs.com

Teva Canada Ltd.

30 Novopharm Court

Toronto, Ontario M1B 2K9

Telephone: 1-800-268-4127 ext. 1255005

E-mail: phv@tevacanada.com

To correct your mailing address or fax number, contact Triton Pharma Inc. or Teva Canada Ltd.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

• Calling toll-free at 1-866-234-2345; or

• Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

For other health product inquiries related to this communication, please contact Health Canada at:

Marketed Health Products Directorate

E-mail: mhpd_dpsc.public@hc-sc.gc.ca

Telephone: 613-954-6522

Fax: 613-952-7738

Sincerely,

original signed by

Sybil Dahan

President

Triton Pharma Inc.

Bruce Valliant

Director, Medical Affairs

Teva Canada Limited

References:

1. Thai, A. & Prindiville, T. Hepatosplenic T-cell lymphoma and inflammatory bowel disease. J. Crohns Colitis 4, 511-522 (2010).
2. Monographie canadienne d’IMURAN^®. 31 janvier 2013.
3. Monographie canadienne de PURINETHOL^®. 10 septembre 2013.
4. Drini M, et al. Hepatosplenic T-cell lymphoma following infliximab therapy for Crohn's disease. Medical Journal of Australia 2008 189:(8)464-465.
5. Kandiel A, et al. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 2005;54:1121-1125.
6. Rosh JR, et al. Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn’s disease: A cautionary tale? Inflammatory Bowel Diseases 2007;13(8):1024- 1030.
7. Shale M, et al. Hepatosplenic T cell lymphoma in inflammatory bowel disease. Gut 2008;57 (12):1639-1641.
8. Thayu M, et al. Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn Disease. Journal of Pediatric Gastroenterology and Nutrition 2005;40:220-222.