The most commonly reported adverse drug reactions (ADRs), occurring in more than 20 % of the patients, are diarrhea, and skin reactions (including rash, acne, dry skin and pruritus). ADRs usually occur within the first month of therapy and are generally reversible. Approximately 10% of patients had a severe ADR (Common Toxicity Criteria, (CTC) grade 3 or 4). Approximately 3% of patients stopped therapy due to an ADR.
Adverse Drug Reactions (ADRs) have been assigned to the frequency categories in the following table where possible based on the incidence of comparable Adverse Event reports in a pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2462 IRESSA-treated patients). In assigning these frequencies no account was taken of the frequency of reports within the comparative treatment groups or whether the investigator considered it to be related to study medication.
Frequency of ADRs relating to abnormal laboratory values is based on patients with a 2 or more CTC grade change from baseline in the relevant laboratory parameters. (See Table 2.)
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From a phase III double blind clinical trial (1692 patients) comparing IRESSA plus best supportive care (BSC) to placebo plus BSC in patients with advanced NSCLC who had received 1 or 2 prior chemotherapy regimens and were refractory or intolerant to their most recent regimen, the incidence of ILD-type events in the overall population was similar, and approximately 1% in both treatment arms. The majority of ILD-type events reported were from patients of Oriental ethnicity and the ILD incidence among patients of Oriental ethnicity receiving IRESSA therapy and placebo was similar, approximately 3% and 4% respectively. One ILD-type event was fatal, and this occurred in a patient receiving placebo.
In a Post-Marketing Surveillance study in Japan (3350 patients) the reported rate of ILD-type events in patients receiving IRESSA was 5.8%.
In a Japanese Pharmacoepidemiological case control study (see Precautions) in patients with NSCLC, the crude cumulative incidence of ILD (unadjusted for imbalances in patient characteristics) at 12 weeks follow-up was 4.0% in patients receiving IRESSA and 2.1% in those receiving chemotherapy and the adjusted odds ratio (OR) of developing ILD was 3.2 (95% confidence interval (CI) 1.9 to 5.4) for IRESSA versus chemotherapy. An increased risk of ILD on IRESSA relative to chemotherapy was seen predominantly during the first 4 weeks of treatment (adjusted OR 3.8; 95% CI 1.9 to 7.7); thereafter the relative risk was lower (adjusted OR 2.5; 95% CI 1.1 to 5.8).
In a phase III open-label clinical trial (1217 patients) comparing IRESSA to carboplatin/paclitaxel doublet chemotherapy as first-line treatment in selected patients with advanced NSCLC in Asia, the incidence of ILD-type events was 2.6% on the IRESSA treatment arm versus 1.4% on the carboplatin/paclitaxel treatment arm.