Afatinib

GILOTRIF is a kinase inhibitor indicated for: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test. Limitations of Use: Safety and efficacy of GILOTRIF were not established in patients whose tumors have resistant EGFR mutations. Treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy

Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding, and can support cell proliferation in NSCLC.

Recommended dosage: 40 mg orally once daily. Renal impairment: 30 mg orally once daily in patients with severe renal impairment. Instruct patients to take GILOTRIF at least 1 hour before or 2 hours after a meal

None. None.

Diarrhea: Diarrhea may result in dehydration and renal failure. Withhold GILOTRIF for severe and prolonged diarrhea not responsive to anti-diarrheal agents. Bullous and exfoliative skin disorders: Severe bullous, blistering, and exfoliating lesions occurred in 0.2% of patients. Discontinue for life-threatening cutaneous reactions. Withhold GILOTRIF for severe and prolonged cutaneous reactions. Interstitial lung disease (ILD): Occurs in 1.6% of patients. Withhold GILOTRIF for acute onset or worsening of pulmonary symptoms. Discontinue GILOTRIF if ILD is diagnosed. Hepatic toxicity: Fatal hepatic impairment occurs in 0.2% of patients. Monitor with periodic liver testing. Withhold or discontinue GILOTRIF for severe or worsening liver tests. Gastrointestinal perforation: Occurs in 0.2% of patients. Permanently discontinue GILOTRIF in patients who develop gastrointestinal perforation.

The following clinically significant adverse reactions are described elsewhere in the labeling: Diarrhea Bullous and Exfoliative Skin Disorders Interstitial Lung Disease Hepatic Toxicity Gastrointestinal Perforation Keratitis Most common adverse reactions (≥20%) were diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus.

P-glycoprotein (P-gp) Inhibitors: Co-administration of P-gp inhibitors can increase afatinib exposure. Reduce GILOTRIF by 10 mg per day if not tolerated. P-gp Inducers: Co-administration of chronic P-gp inducers orally can decrease afatinib exposure. Increase GILOTRIF by 10 mg per day as tolerated. Effect of P-glycoprotein (P-gp) Inhibitors and Inducers Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib. Reduce GILOTRIF daily dose as recommended. Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John's wort) with GILOTRIF can decrease exposure to afatinib. Increase GILOTRIF daily dose as recommended.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15° to 30°C (59° to 86°F). Dispense medication in the original container to protect from exposure to high humidity and light.