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Erlotinib Linked to Deaths in Patients With Hepatic Impairment, Advanced Solid Tumours

OTTAWA, Ontario -- December 18, 2008 -- Hoffmann-La Roche Limited, in consultation with Health Canada, is informing healthcare professionals of important new safety information regarding the use of erlotinib (Tarceva) in patients with moderate hepatic impairment and advanced solid tumours.

A review of a pharmacokinetic study in patients with advanced solid tumours comparing patients with moderate hepatic impairment (Child-Pugh Score 7-9) and those with normal hepatic function showed that 10 of the 15 patients with moderate hepatic impairment died during treatment or within 30 days of the last dose of erlotinib. Of those 10 patients, 5 died within 1 month of initiating erlotinib daily continuous treatment.

Reduced doses should be considered for subjects with moderate hepatic impairment. Hepatic function should be closely monitored in patients with pre-existing liver disease or concomitant hepatotoxic medications.

Erlotinib dosing should be interrupted if significant changes in liver function tests are observed. Safety of erlotinib in subjects with severe hepatic dysfunction has not been studied.

Of the patients who died, 2 were the result of rapidly progressing liver failure including 1 patient with haepatorenal syndrome. Laboratory findings of hepatic failure and/or renal failure were also observed in at least 4 patients out of the remaining 8 patients.

Of the 10 patients who died, 6 had baseline total bilirubin > 3 x ULN, suggesting severe, rather than moderate, hepatic impairment, highlighting the limitations of utilising the Child-Pugh criteria in an oncology patient population.

All patients had hepatic impairment due to advanced cancer with liver involvement such as hepatocellular carcinoma, cholangiocarcinoma, or liver metastases.

The erlotinib Product Monograph is currently being reviewed by Health Canada in conjunction with the manufacturer regarding the information mentioned above, and will be updated accordingly.

Any occurrence of serious and/or unexpected adverse reactions in patients receiving erlotinib should be reported to Hoffmann-La Roche Limited, or Health Canada at the following addresses:

Hoffmann-La Roche Limited
Drug Safety Department
2455 Meadowpine Boulevard
Mississauga, Ontario, L5N 6L7
or call toll free at: 1-888-762-4388
or Fax at: 905-542-5864
mississauga.drug_safety@roche.com

Canada Vigilance Program
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
Ottawa, Ontario, K1A 0K9
Tel: 613-957-0337 or Fax: 613-957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866-234-2345
Fax: 866-678-6789
CanadaVigilance@hc-sc.gc.ca

The adverse reactions reporting form and guidelines can be found here:
http://www.hc-sc.gc.ca/dhp-mps/medeff/report-declaration/form/ar-ei_form_e.html
http://www.hc-sc.gc.ca/dhp-mps/medeff/report-declaration/guide/ar-ei_guide-ldir_e.html

SOURCE: Health Canada