Afatinib

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.

• 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 ( 1.1 ) Limitations of Use : Safety and efficacy of GILOTRIF were not established in patients whose tumors have resistant EGFR mutations ( 1.1 ) Treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy ( 1.2 ) 1.1 EGFR Mutation-Positive, Metastatic Non-Small Cell Lung Cancer GILOTRIF is indicated for the 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 [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) , Clinical Studies (14.1) ]. Limitations of Use : The safety and efficacy of GILOTRIF have not been established in patients whose tumors have resistant EGFR mutations [see Clinical Studies (14.1) ].ICD-10: C34.90

• None. None.contraindicated

Recommended dosage : 40 mg orally once daily ( 2.2 ) Renal impairment : 30 mg orally once daily in patients with severe renal impairment ( 2.4 , 8.6 , 12.3 ) Instruct patients to take GILOTRIF at least 1 hour before or 2 hours after a meal ( 2.2 ) 2.1 Patient Selection for Non-Resistant EGFR Mutation-Positive Metastatic NSCLC Select patients for first-line treatment of metastatic NSCLC with GILOTRIF based on the presence of non-resistant EGFR mutations in tumor specimens [see Clinical Pharmacology (12.1) , Clinical Studies (14.1) ]. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Dosage The recommended dosage of GILOTRIF is 40 mg orally once daily until disease progression or no longer tolerated by the patient. Take GILOTRIF at least 1 hour before or 2 hours after a meal. Do not take a missed dose within 12 hours of the next dose. 2.3 Dosage Modifications for Adverse Reactions Withhold GILOTRIF for: Grade* 3 or higher adverse reactions Diarrhea of Grade 2 persisting for 2 or more consecutive days while taking anti-diarrheal medication [see Warnings and Precautions (5.1) ] Cutaneous reactions of Grade 2 that are prolonged (lasting more than 7 days) or intolerable [see Warnings and Precautions (5.2) ] * National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v 3.0 Resume treatment when the adverse reaction fully resolves, returns to baseline, or improves to Grade 1.

Diarrhea : Diarrhea may result in dehydration and renal failure. Withhold GILOTRIF for severe and prolonged diarrhea not responsive to anti-diarrheal agents. ( 2.3 , 5.1 ) 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. ( 2.3 , 5.2 ) 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. ( 2.3 , 5.3 ) 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. ( 2.3 , 5.4 ) Gastrointestinal perforation : Occurs in 0.2% of patients. Permanently discontinue GILOTRIF in patients who develop gastrointestinal perforation. ( 2.3 , 5.5 ) Keratitis : Occurs in 0.7% of patients. Withhold GILOTRIF for keratitis evaluation. Withhold or discontinue GILOTRIF for confirmed ulcerative keratitis. ( 2.3 , 5.6 ) Embryo-fetal toxicity : Can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.7 ) 5.1 Diarrhea Diarrhea has resulted in dehydration with or without renal impairment across the clinical experience; some cases were fatal.

The following clinically significant adverse reactions are described elsewhere in the labeling: Diarrhea [see Warnings and Precautions (5.1) ] Bullous and Exfoliative Skin Disorders [see Warnings and Precautions (5.2) ] Interstitial Lung Disease [see Warnings and Precautions (5.3) ] Hepatic Toxicity [see Warnings and Precautions (5.4) ] Gastrointestinal Perforation [see Warnings and Precautions (5.5) ] Keratitis [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥20%) were diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the Warnings and Precautions section reflect exposure to GILOTRIF for clinically significant adverse reactions in 4257 patients enrolled in LUX-Lung 3 (n=229) and LUX-Lung 8 (n=392), and 3636 patients with cancer enrolled in 42 studies of GILOTRIF administered alone or in combination with other anti-neoplastic drugs at GILOTRIF doses ranging from 10-70 mg daily or at doses 10-160 mg in other regimens. The mean exposure was 5.5 months.

Lactation : Advise women not to breastfeed ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , GILOTRIF can cause fetal harm when administered to a pregnant woman. There are no available data on the use of GILOTRIF in pregnant women. Administration of afatinib to pregnant rabbits during organogenesis at exposures approximately 0.2 times the exposure in humans at the recommended dose of 40 mg daily resulted in embryotoxicity and, in rabbits showing maternal toxicity, increased abortions at late gestational stages (see Data ) . Advise a pregnant woman of the potential risk to a fetus . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study in rabbits, administration of afatinib to pregnant animals at doses of 5 mg/kg (approximately 0.2 times the exposure by AUC at the recommended human dose of 40 mg daily) or greater during the period of organogenesis caused increased post-implantation loss, and in animals showing maternal toxicity, abortion at late gestational stages.

Metabolism

Absorption Following oral administration of GILOTRIF tablets, time to peak afatinib plasma concentrations (T max ) is 2 to 5 hours. Maximum concentration (C max ) and area under the concentration-time curve from time zero to infinity (AUC 0-INF ) values increased slightly more than dose proportional in the range of 20 to 50 mg.

Overdose was reported in 2 healthy adolescents each of whom ingested 360 mg of GILOTRIF (as part of a mixed-drug ingestion) resulting in nausea, vomiting, asthenia, dizziness, headache, abdominal pain, and elevated amylase [<1.5 times upper limit of normal (ULN)]. Both subjects recovered.

• Jul 12, 2013NDANDA201292Boehringer Ingelheim

1. 1Diarrhoea2,10932%
2. 2Malignant Neoplasm Progression1,68426%
3. 3Rash88013%
4. 4Death5157.9%
5. 5Nausea4837.4%
6. 6Stomatitis4837.4%
7. 7Decreased Appetite4496.9%
8. 8Vomiting4066.2%
9. 9Paronychia3535.4%
10. 10Dehydration3164.8%
11. 11Fatigue2924.5%
12. 12Off Label Use2744.2%
13. 13Metastases To Central Nervous System2684.1%
14. 14Asthenia2353.6%
15. 15Drug Ineffective2293.5%

Recent PubMed references pinned to Afatinib as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Acquired Resistance to Afatinib Mediated by EGFR T790M in Lung Adenocarcinoma Patients Harboring EGFR-KDD: A Case Report and Literature Review.
  Current oncology (Toronto, Ont.) · 2026 · Liu Q, Lv L, Pang G, et al.
  PMID 42041733DOI 10.3390/curroncol33040214
• Real-World Outcomes of Sequential Afatinib and Osimertinib Versus Afatinib and Chemotherapy in EGFR-Mutant NSCLC: Taiwan Multicenter GIANT Study.
  Targeted oncology · 2026 · Ko HW, Liao YT, Liang SK, et al.
  PMID 41862776DOI 10.1007/s11523-026-01203-6
• Efficacy and safety findings of the EXTRA study in older adult EGFR-mutant lung cancer patients receiving afatinib as first-line treatment.
  Scientific reports · 2026 · Morikawa K, Takata S, Tanaka H, et al.
  PMID 41673455DOI 10.1038/s41598-026-38944-3
• First-Line Afatinib 30 mg Versus 40 mg in Non-small Cell Lung Cancer Patients With Uncommon EGFR Mutations: Real-world Efficacy and Tolerability in Taiwan.
  Anticancer research · 2026 · Hung HY, Lee TH, Chuang CH, et al.
  PMID 41617459DOI 10.21873/anticanres.17999
• Afatinib alters DNA methylation and Paneth-like differentiation markers in Caco-2 cells.
  Advances in biological regulation · 2026 · Uemura I, Takahashi-Suzuki N, Satoh T, et al.
  PMID 41616404DOI 10.1016/j.jbior.2026.101146
• Afatinib inhibits esophageal squamous cell carcinoma by regulating ferroptosis and NRF2 protein homeostasis.
  International immunopharmacology · 2026 · Liao Y, Chen W, Sun Z, et al.
  PMID 41520560DOI 10.1016/j.intimp.2025.116131
• Afatinib exerts an inhibitory effect on T cell-mediated cytotoxicity.
  Cancer immunology, immunotherapy : CII · 2026 · Yokomura M, Nagano S, Kawamoto H, et al.
  PMID 41484217DOI 10.1007/s00262-025-04279-7
• Combined treatment of TKIs with Cilengitide overcomes afatinib-resistance in EGFR-mutated NSCLC cells.
  Molecular biology reports · 2025 · Kang HE, Seo Y, Kim Y, et al.
  PMID 41460535DOI 10.1007/s11033-025-11405-2

The 10 most recently updated of 241 ClinicalTrials.gov registrations naming Afatinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study to Evaluate Efficacy and Safety of Firmonertinib Compared With Investigator's Choice of EGFR Inhibitor as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic NSCLC With EGFR P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations
  Recruiting · Phase 3 · Interventional · 480 enrolled · ArriVent BioPharma, Inc.
  NCT07185997updated 2026-06-08
• Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
  Active not recruiting · Phase 2 · Interventional · 6,452 enrolled · National Cancer Institute (NCI)
  NCT02465060updated 2026-06-03
• Exploratory Study of Inhaled Afatinib Dimaleate PK Profile
  Terminated · Phase 1 · Interventional · 4 enrolled · Petrov, Andrey
  NCT06897735updated 2026-06-03
• Testing Afatinib as Potentially Targeted Treatment in Cancers With EGFR Genetic Changes (MATCH - Subprotocol A)
  Active not recruiting · Phase 2 · Interventional · 19 enrolled · National Cancer Institute (NCI)
  NCT06385483updated 2026-05-28
• Afatinib in Patients With Fanconi Anemia (FA) and Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
  Recruiting · Phase 1 · Phase 2 · Interventional · 25 enrolled · Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
  NCT06648096updated 2026-05-27
• S1403, Afatinib Dimaleate With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage IV or Recurrent, EGFR Mutation Positive Non-small Cell Lung Cancer
  Completed · Phase 2 · Phase 3 · Interventional · 174 enrolled · SWOG Cancer Research Network
  NCT02438722updated 2026-05-18
• Pemigatinib + Afatinib in Advanced Refractory Solid Tumors
  Recruiting · Phase 1 · Interventional · 70 enrolled · Massachusetts General Hospital
  NCT06302621updated 2026-05-15
• EGFR-mutated Lung Cancer in Randomized Investigator-Initiated Study
  Recruiting · Phase 3 · Interventional · 200 enrolled · Region Skane
  NCT06486142updated 2026-05-14
• A Clinical Trial Comparing Low-Dose RT + Targeted Therapy+ Immunotherapy vs Targeted Therapy+ Immunotherapy Alone as Neoadjuvant Therapy in Operable HNSCC Patients.
  Recruiting · Phase 2 · Interventional · 98 enrolled · West China Hospital
  NCT07040956updated 2026-05-04
• Testing Afatinib as a Potential Targeted Treatment in Cancers With HER2 Genetic Changes (MATCH-Subprotocol B)
  Active not recruiting · Phase 2 · Interventional · 40 enrolled · National Cancer Institute (NCI)
  NCT04439136updated 2026-04-29

Frequently asked questions

How does Afatinib work?

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.

What is Afatinib used for?

According to FDA labeling, Afatinib carries indications including: 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 ( 1.1 ) Limitations of Use : Safety and efficacy of GILOTRIF were not established in patients whose tumors have resistant EGFR mutations ( 1.1 ) Treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy ( 1.2 ) 1.1 EGFR Mutation-Positive, Metastatic Non-Small Cell Lung Cancer GILOTRIF is indicated for the 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 [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) , Clinical Studies (14.1) ]. Limitations of Use : The safety and efficacy of GILOTRIF have not been established in patients whose tumors have resistant EGFR mutations [see Clinical Studies (14.1) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Afatinib?

Afatinib is classified as Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, Kinase Inhibitor, Protein Kinase Inhibitors, Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Afatinib?

Afatinib is marketed under brand names including Gilotrif.

What are the contraindications for Afatinib?

Afatinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.