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Health professional risk communication

Revlimid (lenalidomide) - Risk of Liver Problems - For Health Professionals

Starting date:
December 27, 2013
Posting date:
December 27, 2013
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Drugs
Source of recall:
Health Canada
Issue:
New safety information
Audience:
Healthcare Professionals
Identification number:
RA-37383

This is duplicated text of a letter from Celgene Inc. Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on REVLIMID® (lenalidomide)

December 27, 2013

Dear RevAid® Registered Prescriber, RevAid® Registered Pharmacist and Allied Health Care Professional:

Subject: Association of REVLIMID® (lenalidomide) with the risk of hepatotoxicity

Celgene Inc., in collaboration with Health Canada, would like to inform you of important new safety information which has been added to the Product Monograph for REVLIMID® (lenalidomide) capsules.

REVLIMID® is an antineoplastic and immunomodulatory agent indicated for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities (approval is based on red blood cell transfusion independence response rates). REVLIMID® is also indicated in combination with dexamethasone for the treatment of multiple myeloma (MM) in patients who have received at least one prior therapy.

The following points summarize the updated Product Monograph safety information:

  • In multiple myeloma patients treated with REVLIMID® in combination with dexamethasone, the following severe cases of liver injuries have been reported: acute hepatic failure, toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis, and mixed cytolytic/cholestatic hepatitis. Some of these cases had a fatal outcome.  
  • The mechanism of severe drug-induced hepatotoxicity in REVLIMID® exposed patients is unknown. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors.
  • Liver enzymes should be monitored periodically. REVLIMID® should be stopped if an elevation of liver enzymes is observed. After return to baseline values, treatment at a lower dose may be considered.

The REVLIMID® (lenalidomide capsules) Canadian Product Monograph was revised to include the updated risk information under the WARNINGS AND PRECAUTIONS section.

Safety reviews for REVLIMID® noted a small increase in overall reporting of hepatic-related adverse events in the patient population exposed to lenalidomide. These reports were mostly of liver-related investigations, signs and symptoms. The reporting rate of hepatic failure, fibrosis and cirrhosis, cholestasis and jaundice as well as non-infectious hepatitis was low. There were a few cases with a fatal outcome and most were complicated by advanced malignant disease, previous or active liver disease, and multiple co-morbidities. The mechanisms involved in the physiopathology remain unknown but a causal relationship between lenalidomide and hepatic disorders cannot be excluded.

Co-morbid conditions and other risk factors that may have contributed to the hepatic disorders include a history of hepatic and renal disorders or concurrent liver infection, or concomitant medications known to cause severe liver dysfunction such as acetaminophen. Monitoring of liver function is recommended, particularly when there is a history of, or concurrent, viral liver infection or when lenalidomide is combined with medications known to be associated with liver dysfunction.

A copy of the most up-to-date REVLIMID® Product Monograph can be found at:  http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp or www.RevAid.ca.

Distribution restrictions: REVLIMID® is only available through a controlled distribution program called RevAid®. Under this program, only prescribers and pharmacists registered with the program are able to prescribe and dispense the product. In addition, REVLIMID® can only be dispensed to patients who are registered and  agree to comply with the requirements of the RevAid® program. For more information, please log onto www.RevAid.ca.

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 hepatotoxicity or other serious or unexpected adverse reactions in patients receiving REVLIMID® should be reported to Celgene Inc. or Health Canada.

Suspected adverse reactions can be reported to:
Celgene Inc.
6755 Mississauga Road, Suite 600
Mississauga, ON  L5N 7Y2
Telephone: 1-877-923-5436
Facsimile: 1-289-291-4820
Email: drugsafety-canada@celgene.com

To correct your mailing address or fax number, contact Celgene Inc.

You can report any suspected side effect 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@hc-sc.gc.ca
Telephone: (613) 954-6522
Fax: (613) 952-7738

Sincerely,

original signed by

Dianne Azzarello, BSc. Phm
Senior Director, Pharmacovigilance & Regulatory Affairs