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Exjade (deferasirox) - Proposed Changes to the Canadian Product Monograph - For Health Professionals

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Contact: Bureau of Metabolism, Oncology and Reproductive Sciences

The Health Products and Food Branch (HPFB) posts on the Health Canada web site safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. These advisories may be prepared with Directorates in the HPFB which includes pre-market and post-market areas as well as market authorization holders and other stakeholders. Although the HPFB grants market authorizations or licenses for therapeutic products, we do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional.

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

Health Canada Endorsed Important Safety Information on Exjade (deferasirox)

November 30, 2009

Subject: Use of EXJADE* (deferasirox) in Patients Diagnosed with Myelodysplastic Syndrome (MDS) and in Elderly Patients regarding Renal Events and Gastrointestinal Hemorrhage (Fatal in Rare Cases)

Dear Health Care Professional,

EXJADE* (deferasirox) is indicated in the management of chronic iron overload in patients with transfusion-dependent anemias aged 6 years or older. EXJADE* is also indicated in the management of chronic iron overload in patients with transfusion-dependent anemias aged two to five who cannot be adequately treated with deferoxamine.

Therapy with EXJADE* should be initiated and maintained by physicians experienced in the treatment of chronic iron overload due to blood transfusions.

Review of adverse events for patients treated with EXJADE* suggests a greater risk of kidney failure, gastrointestinal hemorrhage (potentially fatal) and deaths in patients with myelodysplastic syndrome (MDS) and in elderly patients compared to younger patients with other chronic anemias such as β-thalassemia and sickle cell disease. Many of the adverse events reported are common to elderly patients and patients with MDS, making it difficult to draw any conclusions.
Novartis has proposed changes to the Canadian Product Monograph, including a contraindication in high risk myelodysplastic syndrome (MDS) patients and those with advanced malignancies because these patients are not likely to benefit from iron chelation therapy due to the expected rapid progression of their disease.
Risk factors for kidney failure include pre-existing compromised renal function, and it is therefore recommended that creatinine clearance (and/or serum creatinine) be assessed twice before initiating therapy. Weekly monitoring of creatinine clearance (and/or serum creatinine) is recommended in the first month after initiation or modification of therapy, and monthly thereafter. In addition to the existing creatinine clearance contraindication of <60 mL/min, Novartis has proposed to include a contraindication of serum creatinine >2 times the age-appropriate upper limit of normal.
Gastrointestinal hemorrhage is a known adverse reaction of EXJADE*. There have been rare reports of fatal gastrointestinal hemorrhage, especially in elderly patients who had advanced hematologic malignancies and/or low platelet counts.

In the review of death cases in the MDS patient population, it was apparent that approximately two-thirds of the deaths were in patients who had received less than six months of therapy, indicating that patients with advanced disease and a corresponding poor prognosis have been treated with EXJADE*. These patients are unlikely to derive benefit from treatment with EXJADE*.

In clinical trials, elderly patients experienced a higher frequency of adverse reactions than younger patients, and therefore should be monitored closely for adverse reactions that may require a dose adjustment.

Novartis has proposed changes to the Canadian Product Monograph that are currently under review by Health Canada. The proposed changes include (but are not limited to) the following:

EXJADE* is contraindicated in high risk myelodysplastic syndrome (MDS) patients, any other MDS patient with a life expectancy < 1 year, and patients with other hematological and non-hematological malignancies who are not expected to benefit from chelation therapy due to the rapid progression of their disease.
In addition to monitoring serum creatinine, it is now also recommended that creatinine clearance be assessed twice before initiating therapy. Weekly monitoring of creatinine clearance (and/or serum creatinine) is recommended in the first month after initiation or modification of therapy, and monthly thereafter. EXJADE* is contraindicated in patients with serum creatinine >2 times the age-appropriate upper limit of normal.

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 serious or unexpected adverse reactions in patients receiving EXJADE* should be reported to Novartis or Health Canada at the following addresses:

Novartis Pharmaceuticals Canada Inc.
385 Bouchard Blvd.
Dorval (QC) H9S 1A9
Telephone: 1-877-631-6775 x 3425 (Drug Safety & Epidemiology)

Any suspected adverse reaction can also be reported to:
Canada Vigilance Program
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701D
Ottawa, Ontario, K1A 0K9
Telephone: 613-957-0337 or Fax: 613-957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Telephone: 1-866-234-2345
Fax: 1-866-678-6789
CanadaVigilance@hc-sc.gc.ca

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

For other inquiries related to this communication, please contact Health Canada at:
Bureau of Metabolism, Oncology and Reproductive Sciences
Therapeutic Products Directorate
E-mail: BMORS_Enquiries@hc-sc.gc.ca
Telephone: 613-941-3171
Fax: 613-941-1365

Your professional commitment in this regard has an important role in protecting the well being of your patients by contributing to early signal detection and informed drug use.

Should you have medical enquiries regarding EXJADE*, please contact our Medical Information Department at 1-800-363-8883.

For more information please consult the EXJADE* Prescribing Information and Consumer Information on our Website.