Does Iressa (gefitinib) cause side effects?
It works by preventing lung cancer cells from growing and multiplying. Many cells, including cancer cells, have receptors on their surfaces for epidermal growth factor (EGF), a protein that is normally produced by the body and that promotes the growth and multiplication of cells.
When EGF attaches to epidermal growth factor receptors (EGFRs), it causes an enzyme called tyrosine kinase to become active within the cells. Tyrosine kinase triggers chemical processes that cause the cells, including cancer cells, to grow, multiply, and spread.
Iressa attaches to EGFRs and thereby blocks the attachment of EGF and the activation of tyrosine kinase. This mechanism for stopping cancer cells from growing and multiplying is very different from the mechanisms of chemotherapy and hormonal therapy.
Common side effects of Iressa include
- skin reactions,
- nail disorders,
- inflammation of the lining of the mouth,
- decreased appetite, and
- eye irritation.
Serious side effects of Iressa include
- interstitial lung disease (symptoms include new or worsening cough, fever, or difficulty in breathing) and
- severe or persistent diarrhea,
- loss of appetite, or
Patients who receive drugs that increase an enzyme in the liver called CYP 3A4 that destroys Iressa (for example, rifampin or phenytoin) may need a higher dose of Iressa to maintain the effectiveness of Iressa.
Similarly, patients who receive drugs that reduce CYP 3A4, for example, ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, ritonavir, nelfinavir, indinavir, nefazodone, as well as grapefruit juice, may need a lower dose of Iressa to prevent side effects from increased levels of Iressa.
What are the important side effects of Iressa (gefitinib)?
About one in one hundred persons receiving gefitinib develop a potentially serious lung condition called interstitial lung disease that causes inflammation within the lung. Therefore, patients taking gefitinib who develop new or worsening cough, fever, or difficulty in breathing should contact their physician immediately.
Eye irritation has been observed in patients receiving gefitinib, and patients who develop the onset of new eye symptoms should contact their physician.
All patients taking gefitinib should seek medical advice promptly if they develop severe or persistent
Iressa (gefitinib) side effects list for healthcare professionals
The following adverse drug reactions are discussed in more detail in other sections of the labeling:
- Interstitial Lung Disease
- Gastrointestinal Perforation
- Severe or Persistent Diarrhea
- Ocular Disorders including Keratitis
- Bullous and Exfoliative Skin Disorders
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
- 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
- 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|
|Iressa (N=1126)||Placebo (N=562)|
|All Grades||Grade 3 and 4||All Grades||Grade 3 and 4|
|Skin and subcutaneous tissue disorders|
|Metabolism and nutrition disorders|
|Conjunctivitis/ blepharitis/dry eye5||6%||0%||3.2%||0%|
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 toxicity, Xeroderma
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
|Grade 3 and 4
|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|
1 Patients 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.
What drugs interact with Iressa (gefitinib)?
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.
- 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.
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.
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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.
Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.