KETOCONAZOLE - Risk of Potentially Fatal Liver Toxicity - For Health Professionals

Starting date:

June 19, 2013

Posting date:

June 19, 2013

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

Important Safety Information

Audience:

Healthcare Professionals

Identification number:

RA-34173

This is duplicated text of a letter from Apotex Inc. and Teva Canada Limited. Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on KETOCONAZOLE

June 19, 2013

Subject: KETOCONAZOLE and the Risk of potentially Fatal Liver Toxicity

Dear Health Care Professional,

The manufacturers of KETOCONAZOLE, in collaboration with Health Canada, would like to inform you of revisions to the Product Monograph for KETOCONAZOLE regarding the risk of potentially fatal liver toxicity.

KETOCONAZOLE has been associated with rare cases of serious hepatotoxicity including liver failure and death.  This risk was also observed in patients with no pre-existing liver disease and no serious underlying medical conditions. Hepatotoxicity and death have been reported to occur at recommended doses and with treatment courses longer than 10 days. 

The Warnings’ sections of the Product Monographs have been updated to include the following additional instructions:

• KETOCONAZOLE tablets are indicated for the treatment of serious or life threatening systemic fungal infections and should not be considered for mild to moderate infections.
• Oral KETOCONAZOLE has been associated with hepatic toxicity, including cases with fatal outcomes.
• Liver function tests should be performed in all patients before starting treatment, at week 2 and 4, and monthly thereafter.
• Treatment should be stopped if liver parameters are elevated (> 3 times the normal limit) or if patients develop clinical signs or symptoms consistent with liver disease such as anorexia, nausea, vomiting, jaundice, fatigue, abdominal pain, dark urine, or pale stools.

Healthcare practitioners should consider the risk of fatal liver toxicity with KETOCONAZOLE when prescribing antifungal treatment for patients who are already at risk for liver toxicity. Patients using KETOCONAZOLE concurrently with potentially hepatotoxic drugs should be carefully monitored, especially in those expected to be on prolonged therapy or at risk for hepatotoxicity.

The profile of KETOCONAZOLE is continually monitored and reassessed as new information becomes available through the literature, clinical studies, spontaneous reports, and safety database searches.

Managing marketed health product-related adverse reactions depends on healthcare 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 liver toxicity or other serious or unexpected adverse reactions in patients receiving KETOCONAZOLE should be reported to either of the respective manufacturers (Apotex Inc. or Teva Canada Limited) or Health Canada.

APOTEX INC.
150 Signet Drive
Weston, Ontario
M9L 1T9
Phone: 1-800-667-4708
Fax: 1-416-401-3884

Teva Canada Limited
30 Novopharm Court
Toronto, Ontario
M1B 2K9
Phone: 1-800-268-4127 Ext. 1255005 (English) or 1-877-777-9117 (French)
Fax:  1-416-355-4472

To correct your mailing address or fax number, contact Apotex Inc. or Teva Canada Limited.

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

Yours sincerely,

original signed by

Colin D’Cunha
Director, Global Medical Affairs
Apotex Inc.

Bruce Valliant
Director, Medical Affairs
Teva Canada Limited

References:

1. Apo-Ketoconazole Product Monograph. Apotex Inc. 2013.
2. Novo-Ketoconazole Product Monograph. Teva Canada Limited. 2013.
3. L. A. Garcia Rodriguez, A cohort study on the risk of acute liver injury among users of ketoconazole and other antifungal drugs. Br J Clin Pharmacol 1999, 48, 847–852.