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The following adverse drug reactions are discussed in more detail in other sections of the labeling:
- Interstitial Lung Disease [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Gastrointestinal Perforation [see WARNINGS AND PRECAUTIONS]
- Severe or Persistent Diarrhea [see WARNINGS AND PRECAUTIONS]
- Ocular Disorders including Keratitis [see WARNINGS AND PRECAUTIONS]
- Bullous and Exfoliative Skin Disorders [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of IRESSA is based on the data from 2462 patients with NSCLC who received IRESSA 250 mg daily monotherapy in three randomized clinical studies (Study 2, Study 3 and Study 4). Patients with a history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis that required steroid treatment or any evidence of clinically active interstitial lung disease were excluded from these studies.
Study 2 was a randomized, multicenter, open-label trial in which 1217 patients were randomized to receive first-line treatment for metastatic NSCLC; 607 patients received IRESSA 250 mg daily and 589 patients received carboplatin/paclitaxel. The median duration of treatment with IRESSA was 5.9 months. The study population characteristics were: median age 57 years, age less than 65 years (73%), female (79%), Asian (100%), NSCLC adenocarcinoma histology (100%), never smoker (94%), light ex-smoker (6%), ECOG PS 0 or 1 (90%).
Study 3 was a randomized, multicenter, double-blind, placebo-controlled trial in which 1692 patients were randomized to receive second- or third-line treatment for metastatic NSCLC; of which 1126 patients received IRESSA 250 mg daily and 562 patients received placebo. The median duration of treatment with IRESSA was 2.9 months. The study population characteristics were: median age 62 years, age less than 65 years (60%), female (33%), Caucasian (75%), Asian (21%), NSCLC adenocarcinoma histology (48%), never smoker (22%), ECOG PS 0 or 1 (65%), PS 2 (29%), PS 3 (5%) and two or more prior therapies (51%).
Study 4 was a randomized, multicenter, open-label trial in which 1466 patients were randomized to receive second-line treatment for metastatic NSCLC; 729 patients received IRESSA 250 mg daily and 715 patients received docetaxel. The median duration of treatment with IRESSA was 2.4 months. The study population characteristics were: median age 61 years, age less than 65 years (61%), female (36%), Caucasian (79%), Asian (21%), NSCLC adenocarcinoma histology (54%), never smoker (20%), ECOG PS 0 or 1 (88%) and two or more prior therapies (16%).
The pooled safety database from the three randomized trials was used to evaluate for serious and uncommon adverse drug reactions. Common adverse reactions were evaluated in Study 3. The most frequent adverse reactions in Study 3 (incidence of > 20% and greater than placebo) reported in IRESSA-treated patients were skin reactions (47%) and diarrhea (29%). The most frequent fatal adverse reactions in IRESSA-treated patients were respiratory failure (0.9%), pneumonia (0.8%), and pulmonary embolism (0.5%).
Approximately 5% of IRESSA-treated patients and 2.3% of placebo-treated patients discontinued treatment due to an adverse event. The most frequent adverse reactions that led to discontinuation in patients treated with IRESSA were nausea (0.5%), vomiting (0.5%) and diarrhea (0.4%).
Table 1: Selected Adverse Drug Reactions Occurring
with an Incidence Rate ≥ 5% and an Increase of > 2% of IRESSA-treated
Patients in Study 3
|Adverse Reaction||Percentage (%) of patients|
|All Grades||Grade 3 and 4||All Grades||Grade 3 and 4|
|Skin and subcutaneous tissue disorders|
|Metabolism and nutrition disorders|
|1 Includes Acne, Acne pustular, Dermatitis,
Dermatitis acneiform, Dermatitis exfoliative, Drug eruption, Dry skin,
Erythema, Exfoliative rash, Folliculitis, Pruritus, Pruritus generalized, Rash,
Rash erythematous, Rash generalized, Rash macular, Rash maculo-papular, Rash
papular, Rash pruritic, Rash pustular, Rash vesicular, Skin exfoliation, Skin
2 Includes Ingrowing nail, Nail bed infection, Nail disorder, Nail infection, Onychoclasis, Onycholysis, Paronychia
3 Includes Diarrhea, Feces soft, Frequent bowel movements
4 Includes Aphthous stomatitis, Cheilitis, Glossodynia, Mouth ulceration, Mucosal inflammation, Oral mucosal blistering, Stomatitis, Tongue disorder, Tongue ulceration
5 Includes Blepharitis, Conjunctival hyperemia, Conjunctivitis, Dry eye, Eye irritation, Eye pruritus, Eye swelling, Eyelid irritation, Eyelid edema, Eyelids pruritus
Table 2 : Treatment Emergent Laboratory Abnormalities
Occurring More Frequently in IRESSA- Treated Patients in Study 3
|All Grades %||Grade 3 and 4 %||All Grades %||Grade 3 and 4 %|
|Alanine aminotransferase increased1||38%2||2.4%||23%2||1.4%4|
|Aspartate aminotransferase increased1||40%3||2.0%||25%3||1.3%5|
|1Patients were allowed to enter the clinical study with lab
values of ALT or AST CTCAE grade 1 or 2
2 14% gefitinib patients and 10% placebo patients were CTC grade 1 or 2 ALT at baseline
3 15% gefitinib patients and 12% placebo patients were CTC grade 1 or 2 AST at baseline
4 0.2% of placebo patients were CTC grade 3 at baseline
5 0.4% of placebo patients were CTC grade 3 at baseline
The following adverse reactions have been reported with IRESSA across NSCLC trials (Study 2, Study 3 and Study 4) and are not listed elsewhere in Section 6: nausea (18%), asthenia (17%), pyrexia (9%), alopecia (4.7%), hemorrhage (including epistaxis and hematuria) (4.3%), dry mouth (2%), dehydration (1.8%), allergic reactions including angioedema and urticaria (1.1%), elevations in blood creatinine (1.5%), and pancreatitis (0.1%).
The following adverse reactions have been identified during post-approval use of IRESSA. 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.
Read the Iressa (getfitinib) Side Effects Center for a complete guide to possible side effects
Drugs Affecting Gefitinib Exposure
Drugs that are strong inducers of CYP3A4 increase the metabolism of gefitinib and decrease gefitinib plasma concentrations. Increase IRESSA to 500 mg daily in patients receiving a strong CYP3A4 inducer (e.g., rifampicin, phenytoin, or tricyclic antidepressant) and resume IRESSA at 250 mg 7 days after discontinuation of the strong inducer [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].
Drugs that are strong inhibitors of CYP3A4 (e.g., ketoconazole and itraconazole) decrease gefitinib metabolism and increase gefitinib plasma concentrations. Monitor adverse reactions when administering strong CYP3A4 inhibitors with IRESSA.
Drugs Affecting Gastric pH
Drugs that elevate gastric pH (e.g., proton pump inhibitors, histamine H2-receptor antagonists, and antacids) may reduce plasma concentrations of gefitinib. Avoid concomitant use of IRESSA with proton pump inhibitors, if possible. If treatment with a proton-pump inhibitor is required, take IRESSA 12 hours after the last dose or 12 hours before the next dose of the proton-pump inhibitor. Take IRESSA 6 hours after or 6 hours before an H2-receptor antagonist or an antacid [see CLINICAL PHARMACOLOGY].
Hemorrhage In Patients taking Warfarin
International Normalized Ratio (INR) elevations and/or hemorrhage have been reported in some patients taking warfarin while on IRESSA therapy. Patients taking warfarin should be monitored regularly for changes in prothrombin time or INR.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 7/15/2015
Additional Iressa Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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