- It 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 Limitation of Use: Safety and efficacy of it 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. 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.
- Recommended dose: 40 mg orally, once daily · Renal impairment: 30 mg orally, once daily in patients with severe renal impairment · Instruct patients to take it at least 1 hour before or 2 hours after a meal .
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 Afatinib can increase exposure to Afatinib. Concomitant taking of P- gp inducers (including but not limited to Rifampicin, Carbamazepine, Phenytoin, Phenobarbital, and St. John's wort) with Afatinib can decrease exposure to Afatinib.
- Diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus.
- Lactation: Advise women not to breastfeed
Overdose was reported in 2 healthy adolescents each of whom ingested 360 mg of Anib (as part of a mixed-drug ingestion) resulting in nausea, vomiting, asthenia, dizziness, headache, abdominal pain, and elevated amylase. Both subjects recovered.
Store below 30°C in a cool and dry place, away from sunlight. Keep out of reach of children.
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