.
Bullous and Exfoliative Skin Disorders
Grade 3 cutaneous reactions characterized by bullous, blistering, and exfoliating lesions occurred in 6 (0.15%) of the 3865 patients who received Gilotrif across clinical trials [see Adverse Reactions (6.1)]. In Study 1, the overall incidence of cutaneous reactions consisting of rash, erythema, and acneiform rash was 90%, and the incidence of Grade 3 cutaneous reactions was 16%. In addition, the incidence of Grade 1-3 palmar-plantar erythrodysesthesia syndrome was 7%. Discontinue Gilotrif in patients who develop life-threatening bullous, blistering, or exfoliating lesions [see Dosage and Administration (2.3)]. For patients who develop prolonged Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable Grade 2, or Grade 3 cutaneous reactions, withhold Gilotrif until the adverse reaction resolves to Grade 1 or less, and resume Gilotrif with appropriate dose reduction [see Dosage and Administration (2.3)].
Interstitial Lung Disease (ILD)
ILD or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress syndrome, or alveolitis allergic) occurred in 1.5% of the 3865 patients who received Gilotrif across clinical trials; of these, 0.4% were fatal. The incidence of ILD appeared to be higher in patients of Asian ethnicity (2.1%) as compared to non-Asians (1.2%). In Study 1, the incidence of Grade ≥3 ILD was 1.3% and resulted in death in 1% of Gilotrif-treated patients.
Withhold Gilotrif during eva luation of patients with suspected ILD, and discontinue Gilotrif in patients with confirmed ILD [see Dosage and Administration (2.3)].
Hepatic Toxicity
In 3865 patients who received Gilotrif across clinical trials, 10.1% had liver test abnormalities, of which 7 (0.18%) were fatal. In Study 1, liver test abnormalities of any grade occurred in 17.5% of the patients treated with Gilotrif.
Obtain periodic liver testing in patients during treatment with Gilotrif. Withhold Gilotrif in patients who develop worsening of liver function [see Dosage and Administration (2.3)]. In patients who develop severe hepatic impairment while taking Gilotrif, treatment should be discontinued.
Keratitis
Keratitis, characterized as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye occurred in 0.8% of patients treated with Gilotrif among 3865 patients across clinical trials. Keratitis was reported in 5 (2.2%) patients in Study 1, with Grade 3 in 1 (0.4%). Withhold Gilotrif during eva luation of patients with suspected keratitis, and if diagnosis of ulcerative keratitis is confirmed, treatment with Gilotrif should be interrupted or discontinued [see Dosage and Administration (2.3)]. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered. Gilotrif should be used with caution in patients with a history of keratitis, ulcerative keratitis, or severe dry eye [see Adverse Reactions (6.1)]. Contact lens use is also a risk factor for keratitis and ulceration.
Embryofetal Toxicity
Based on its mechanism of action, Gilotrif can cause fetal harm when administered to a pregnant woman. Afatinib was embryotoxic and, in animals with maternal toxicity, led to abortions at late gestational stages in rabbits at doses of 5 mg/kg (approximately 0.2 times the human exposure at the recommended dose of 40 mg daily) or greater. If this drug is used during pregnancy, or if the patie |
