Anib 40mg

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. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methods. The most commonly found of these mutations are exon 21 L858R substitutions and exon 19 deletions.

Afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild type EGFR and in those expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.

Treatment with afatinib resulted in inhibition of tumor growth in nude mice implanted with tumors either overexpressing wild type EGFR or HER2 or in an EGFR L858R/T790M double mutant model.

Patient Selection for EGFR Mutation-Positive Metastatic NSCLC: Patients should be selected for first-line treatment of metastatic NSCLC with GILOTRIF based on the presence of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations in tumor specimens.

Recommended Dose: The recommended dose of Afatinib is 40 mg orally, once daily until disease progression or no longer tolerated by the patient.

Severe Renal Impairment: The recommended dose of Afatinib in patients with severe renal impairment (estimated glomerular filtration rate 15 to 29 mL/min /1.73 m²) is 30 mg orally, once daily. Afatinib should be taken at least 1 hour before or 2 hours after a meal. A missed dose should not be taken within 12 hours of the next dose. Or, as directed by the registered physicians.

Pediatric Use: Safety and effectiveness of Afatinib in pediatric patients have not been established.