Letter dated December 12, 2008 published on the Health Canada website on erlotinib adverse effects:
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 > 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.
Source: The use of Tarceva (erlotinib) in patients with moderate hepatic impairment and advanced solid tumours – For Health Professionals. PDF full text