The use of Tarceva (erlotinib) in patients with moderate hepatic impairment and advanced solid tumours - For Health Professionals

Starting date:

December 12, 2008

Posting date:

December 17, 2008

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-170001900

This is duplicated text of a letter from Hoffmann-La Roche Limited.

Contact the appropriate company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on Tarceva (erlotinib)

December 12, 2008

Subject: The use of Tarceva^® (erlotinib) in patients with moderate hepatic impairment and advanced solid tumours

Dear Health Care Professional,

Hoffmann-La Roche Limited, in consultation with Health Canada would like to inform prescribers of important new safety information regarding the use of Tarceva^® (erlotinib) in patients with moderate hepatic impairment and advanced solid tumors.

Tarceva^® is a Human Epidermal Growth Factor Receptor Type 1/Epidermal Growth Factor Receptor (HER1/EGFR) tyrosine kinase inhibitor. It is authorized as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen, and whose EGFR expression status is positive or unknown.

Based on review of a pharmacokinetic study in patients with advanced solid tumours comparing patients with moderate hepatic impairment and those with normal hepatic function:

• Ten of the fifteen patients with moderate hepatic impairment died during treatment or within 30 days of the last dose of Tarceva. Five of the ten subjects died within one month of initiating Tarceva daily continuous treatment.
• Reduced Tarceva 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. Tarceva dosing should be interrupted if significant changes in liver function tests are observed.
• Safety of Tarceva in subjects with severe hepatic dysfunction has not been studied.

A pharmacokinetic study was conducted in patients with advanced solid tumors comparing patients with moderate hepatic impairment (Child-Pugh Score 7-9) and patients with normal hepatic function. Ten of the fifteen patients with hepatic impairment died during treatment or within 30 days of the last Tarceva dose. Two patients died from rapidly progressing liver failure including 1 patient with hepatorenal syndrome. Laboratory findings of hepatic failure and/or renal failure were also observed in at least 4 patients out of the remaining 8 patients. Six out of the 10 patients who died had baseline total bilirubin greater than 3 x ULN suggesting severe, rather than moderate, hepatic impairment, highlighting the limitations of utilizing 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 Tarceva Product Monograph is currently being reviewed by Health Canada in conjunction with the sponsor regarding the information mentioned above, and will be updated accordingly.

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 occurrence of serious and/or unexpected adverse reactions in patients receiving Tarceva 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

Toll free: 1-888-762-4388

Fax: 905-542-5864

Email: mississauga.drug_safety@roche.com

Any suspected adverse reaction can also be reported to:

Canada Vigilance Program

Marketed Health Products Directorate

Health Canada

Address Locator: 0701C

Ottawa, Ontario, K1A 0K9

Tel.: 613-957-0337

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 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 (BMORS)

E-mail: bmors_enquiries@hc-sc.gc.ca

Tel. 613-941-3171

Fax: 613-941-1365

Should you have any questions or require additional information regarding the use of Tarceva, please contact the Drug Information Department at Hoffmann-La Roche Limited at 1-888-762-4388 from 8:30 a.m. to 4:30 p.m. Monday to Friday Eastern Standard Time.

Sincerely,

original signed by

Lorenzo Biondi,

Vice President, Medical and Regulatory Affairs

Hoffmann-La Roche Limited