Interstitial Lung Disease (ILD) ILD or ILD-like adverse drug reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress syndrome, or pulmonary fibrosis) occurred in 1.3% of the 2462 patients who received gefitib across clinical trials; of these, 0.7% were Grade 3 or higher and 3 cases were fatal. Withhold gefitinib and promptly investigate for ILD in any patient who presents with worsening of respiratory symptoms such as dyspnea, cough and fever. Permanently discontinue gefitinib if ILD is confirmed.
In patients who received gefitib across clinical trials, 11.4% of patients had increased alanine aminotransferase (ALT), 7.9% of patients had increased aspartate aminotransferase (AST), and 2.7% of patients had increased bilirubin. Grade 3 or higher liver test abnormalities occurred in 5.1% (ALT), 3.0% (AST), and 0.7% (bilirubin) of patients. The incidence of fatal hepatotoxicity was 0.04%. Obtain periodic liver function testing. Withhold gefitinib in patients with worsening liver function and discontinue in patients with severe hepatic impairment.
Gastrointestinal perforation occurred in three (0.1%) of the 2462 gefitinib-treated patients across clinical trials. Permanently discontinue gefitinib in patients who develop gastrointestinal perforation.
Severe or Persistent
Diarrhea Grade 3 or 4 diarrhea occurred in 3% of 2462 IRESSA-treated patients across clinical trials. Withhold gefitinib for severe or persistent (up to 14 days) diarrhea.
Ocular Disorders including Keratitis
Ocular disorders [keratitis (0.1%), corneal erosion and aberrant eyelash growth (0.2%), conjunctivitis, blephritis and dry eye (6.7%)] occurred in the 2462 gefitinib-treated patients across clinical trials. The incidence of Grade 3 ocular disorders was 0.1%. Interrupt or discontinue gefitinib for severe, or worsening ocular disorders.
Bullous and Exfoliative Skin Disorders
Bullous conditions including toxic epidermal necrolysis, Stevens Johnson syndrome and erythema multiforme have been reported from treatment with gefitinib. Erythema multiforme and dermatitis bullous have been reported in two patients (0.08%) across NSCLC trials (Study 2, Study 3 and Study 4). gefitinib treatment should be interrupted or discontinued if the patient develops severe bullous, blistering or exfoliating conditions.
Based on its mechanism of action and data from animal reproduction studies gefitinib can cause fetal harm when administered to a pregnant woman. In animal reproductive studies, oral administration of gefitinib from organogenesis through weaning resulted in fetotoxicity and neonatal death at doses below the recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with gefitinib and for at least two weeks following completion of therapy.