Label Changes for:
Tarceva (erlotinib) tablets
Changes have been made to the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – April 2010
WARNINGS AND PRECAUTIONS
Use in Pregnancy
- There are no adequate and well-controlled studies in pregnant women using Tarceva. Women of childbearing potential should be advised to avoid pregnancy while on Tarceva. Adequate contraceptive methods should be used during therapy, and for at least 2 weeks after completing therapy. If Tarceva is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Clinical Trial Experience
Non-Small Cell Lung Cancer
- Adverse reactions, regardless of causality, that occurred in at least 3% of patients treated with single-agent Tarceva at 150 mg and at least 3% more often than in the placebo group in the randomized maintenance trial are summarized by NCI-CTC (version 3.0) Grade in Table 1.
- The most common adverse reactions in patients receiving single-agent Tarceva 150 mg were rash and diarrhea. Grade 3/4 rash and diarrhea occurred in 6.0% and 1.8%, respectively, in Tarceva-treated patients. Rash and diarrhea resulted in study discontinuation in 1.2% and 0.5% of Tarceva-treated patients, respectively. Dose reduction or interruption for rash and diarrhea was needed in 5.1% and 2.8% of patients, respectively. In Tarceva-treated patients who developed rash, the onset was within two weeks in 66% and within one month in 81%.
- New Table (1)
- Liver function test abnormalities (including elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin) were observed in patients receiving single-agent Tarceva 150 mg in the Maintenance study. Grade 2 (>2.5 – 5.0 x ULN) ALT elevations occurred in 2% and 1%, and Grade 3 (>5.0 – 20.0 x ULN) ALT elevations were observed in 1% and 0% of TARCEVA and placebo treated patients, respectively. The Tarceva treatment group had Grade 2 (>1.5-3.0 x ULN) bilirubin elevations in 4% and Grade 3 (>3.0-10.0 x ULN) in <1% compared with <1% for both Grades 2 and 3 in the placebo group. Tarceva dosing should be interrupted or discontinued if changes in liver function are severe.
The following adverse reactions have been identified during post approval use of Tarceva. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Skin and subcutaneous tissue disorders: Hair and nail changes, mostly non-serious e.g. hirsutism, eyelash/eyebrow changes, paronychia and brittle and loose nails. Bullous, blistering and exfoliative skin conditions have been reported including cases suggested of Stevens-Johnson syndrome/Toxic epidermal necrolysis.
- Gastrointestinal Disorders: Gastrointestinal perforations.
- Hepatic Disorders: Hepatic failure has been reported in patients treated with single-agent Tarceva or Tarceva combined with chemotherapy.
- Co-administration of Tarceva with omeprazole, a proton pump inhibitor, decreased the erlotinib AUC by 46%.
- Co-administration of Tarceva with 300 mg ranitidine, an H2 receptor antagonist, decreased erlotinib AUC by 33%. When Tarceva was administered with ranitidine 150 mg twice daily (at least 10 h after the previous ranitidine evening dose and 2 h before the ranitidine morning dose), the erlotinib AUC decreased by 15%. If patients need to be treated with an H2-receptor antagonist such as ranitidine, it should be used in a staggered manner. Tarceva must be taken once a day, 10 hours after the H2 receptor antagonist dosing and at least 2 hours before the next dose of H2-receptor antagonist.
USE IN SPECIFIC POPULATIONS
- Tarceva can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised not to become pregnant while being treated with Tarceva.
- Of the total number of patients participating in the randomized NSCLC Maintenance trial, 66% were less than 65 years of age, and 34% of patients were aged 65 years or older. The hazard ratio for overall survival was 0.78 (95% CI: 0.65, 0.95) in patients less than 65 years of age and 0.88 (95% CI: 0.68, 1.15) in patients who were 65 years or older.
- Of the total number of patients participating in the randomized Maintenance trial, 73% were males and 27% females.There were no clinically relevant differences in safety and efficacy based on gender [OS HR = 0.88 (96% CI: 0.74, 1.05) in males and OS HR = 0.64 (95% CI: 0.46, 0.91) in females].
- In the randomized Maintenance trial, 84% of all patients were Caucasian and 15% were Asian. There were no clinically relevant differences in safety and efficacy based on race [OS HR = 0.86 (95% CI: 0.73, 1.01) in Caucasians and OS HR = 0.66 (95% CI: 0.42, 1.05) in Asians].