Gefitinib - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Interstitial lung disease (ILD): ILD occurred in patients taking gefitinib tablets.

Withhold gefitinib tablets for worsening of respiratory symptoms.

Discontinue gefitinib tablets if ILD is confirmed. ( 2.4 , 5.1 ) Hepatotoxicity: Obtain periodic liver function testing.

Withhold gefitinib tablets for Grade 2 or higher for ALT and/or AST elevations.

Discontinue for severe hepatic impairment. ( 2.4 , 5.2 ) Gastrointestinal perforation: Discontinue gefitinib tablets for gastrointestinal perforation. ( 2.4 , 5.3 ) Diarrhea: Withhold gefitinib tablets for Grade 3 or higher diarrhea. ( 2.4 , 5.4 ) Ocular Disorders including Keratitis: Withhold gefitinib tablets for signs and symptoms of severe or worsening ocular disorders including keratitis.

Discontinue for persistent ulcerative keratitis. ( 2.4 , 5.5 ) Bullous and Exfoliative Skin Disorders: Withhold gefitinib tablets for Grade 3 or higher skin reactions or exfoliative conditions. ( 2.4 , 5.6 ) Embryo-fetal Toxicity: Can cause fetal harm.

Advise of potential risk to a fetus and use of effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 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 gefitinib tablets across clinical trials; of these, 0.7% were Grade 3 or higher and 3 cases were fatal.

Withhold gefitinib tablets and promptly investigate for ILD in any patient who presents with worsening of respiratory symptoms such as dyspnea, cough and fever.

Permanently discontinue gefitinib tablets if ILD is confirmed [see Dosage and Administration , Adverse Reactions ] .

5.2 Hepatotoxicity In patients who received gefitinib tablets 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 tablets in patients with worsening liver function and discontinue in patients with severe hepatic impairment [see Dosage and Administration , Adverse Reactions , Use in Specific Populations ].

5.3 Gastrointestinal Perforation Gastrointestinal perforation occurred in three (0.1%) of the 2462 gefitinib tablets-treated patients across clinical trials [see Adverse Reactions ] .

Permanently discontinue gefitinib tablets in patients who develop gastrointestinal perforation [see Dosage and Administration ] .

5.4 Severe or Persistent Diarrhea Grade 3 or 4 diarrhea occurred in 3% of 2462 gefitinib tablets-treated patients across clinical trials.

Withhold gefitinib tablets for severe or persistent (up to 14 days) diarrhea [see Dosage and Administration , Adverse Reactions ] .

5.5 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 tablets-treated patients across clinical trials.

The incidence of Grade 3 ocular disorders was 0.1% [see Adverse Reactions ] .

Interrupt or discontinue gefitinib tablets for severe, or worsening ocular disorders [see Dosage and Administration ] .

5.6 Bullous and Exfoliative Skin Disorders Bullous conditions including toxic epidermal necrolysis, Stevens Johnson syndrome and erythema multiforme have been reported from treatment with gefitinib tablets.

Erythema multiforme and dermatitis bullous have been reported in two patients (0.08%) across NSCLC trials (Study 2, Study 3 and Study 4).

Gefitinib tablets treatment should be interrupted or discontinued if the patient develops severe bullous, blistering or exfoliating conditions.

5.7 Embryo-fetal Toxicity Based on its mechanism of action and data from animal reproduction studies gefitinib tablets can cause fetal harm when administered to a pregnant woman.