EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer: Afatinib is used as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors carry non-resistant EGFR mutations confirmed by an approved diagnostic test.

Limitation of Use: The effectiveness and safety of Afatinib have not been established in patients with tumors that contain resistant EGFR mutations.

Previously Treated, Metastatic Squamous NSCLC: Afatinib is also indicated for patients with metastatic squamous NSCLC whose disease has progressed after platinum-based chemotherapy.

Afatinib irreversibly binds to and blocks the kinase activity of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4), thereby suppressing downstream signaling pathways responsible for tumor growth. Certain EGFR mutations, particularly non-resistant ones, enhance receptor activation and promote cancer cell proliferation. Afatinib effectively inhibits these processes by reducing receptor autophosphorylation and cellular proliferation.

Clinical evidence shows that tumors with specific EGFR mutations—such as exon 19 deletions and exon 21 L858R substitutions—respond well to Afatinib therapy, resulting in tumor shrinkage and reduced cancer progression. Laboratory studies also demonstrate its ability to inhibit growth in cancer cell lines expressing EGFR and HER2. Additionally, animal studies have shown suppression of tumor growth in models with EGFR or HER2 overexpression or specific mutation profiles.

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.

Afatinib, a P-glycoprotein (P-gp) inhibitor and inducer, may interact with drugs that affect P-gp activity. Co-administration with strong P-gp inhibitors (such as Ritonavir, Cyclosporine A, Ketoconazole, Itraconazole, Erythromycin, Verapamil, Quinidine, Tacrolimus, Nelfinavir, Saquinavir, and Amiodarone) can increase Afatinib exposure. Conversely, P-gp inducers (such as Rifampicin, Carbamazepine, Phenytoin, Phenobarbital, and St. John’s wort) may reduce its plasma concentration.

Afatinib should not be used in patients who have known hypersensitivity to Afatinib or any of its components.

Common adverse effects include:

• Diarrhea
• Bullous and exfoliative skin disorders
• Interstitial lung disease
• Hepatic toxicity
• Keratitis

Afatinib may cause fetal harm when administered during pregnancy. There is no sufficient data regarding its use in pregnant or breastfeeding women. Due to the potential risk of serious adverse effects in nursing infants, breastfeeding should be avoided during treatment and for at least 2 weeks after the last dose.

Diarrhea: Severe diarrhea may lead to dehydration and kidney failure. Prompt treatment is necessary, and dose adjustment or discontinuation may be required in severe cases.

Bullous and Exfoliative Skin Disorders: Monitor for severe skin reactions such as blistering or peeling. Discontinue treatment if serious conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis are suspected.

Interstitial Lung Disease (ILD): Rare but serious ILD-like reactions may occur. Treatment should be stopped if ILD is suspected or confirmed.

Hepatic Toxicity: Liver function should be monitored regularly. Dose modification or discontinuation may be required in patients with worsening liver function.

Keratitis: Symptoms such as eye pain, redness, or vision changes should be evaluated. Interrupt or discontinue treatment if keratitis is confirmed.

Overdose may lead to symptoms such as nausea, vomiting, abdominal pain, dizziness, and increased enzyme levels. Supportive treatment is recommended.

Tyrosine Kinase Inhibitor.

Store below 30°C in a cool, dry place, protected from direct sunlight. Keep out of reach of children.