Afatinib
Kinase inhibitors (targeted oncology)
Kinase inhibitors (targeted oncology)High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
A second-generation, irreversible inhibitor of EGFR, HER2 and HER4 for EGFR-mutant lung cancer; diarrhoea and rash are frequent and can be severe.
Also called: BIBW2992
Quick facts
- Group
- Kinase inhibitors (targeted oncology)
- Target
- EGFR tyrosine kinase domain
- Used for
- First-line treatment
- Key effects
- Diarrhoea · Acne-like rash · Mouth sores
- Monitor
- Stool frequency and hydration · Skin and nails
- ATC
- L01EB03
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows afatinib in the ATP pocket of the human EGFR kinase domain, where it forms a covalent bond.
Afatinib binds covalently to the kinase domains of EGFR (ErbB1), HER2 (ErbB2) and HER4 (ErbB4) and irreversibly blocks their autophosphorylation, shutting down ErbB-family signalling. It is most active in lung tumours with non-resistant activating EGFR mutations; because it also blocks normal EGFR in skin and gut, rash and diarrhoea are common.
- Enters the ATP pocket of EGFR, HER2 and HER4
- Forms a covalent, irreversible bond
- ErbB autophosphorylation and signalling stop
- Also hits normal EGFR: rash and diarrhoea
Indications
- First-line treatment of metastatic non-small cell lung cancer with non-resistant EGFR mutations; also squamous non-small cell lung cancer after platinum chemotherapy. Lung cancer →
Adverse effects
Common
- Diarrhoea
- Acne-like rash, dry skin, itching
- Mouth sores (stomatitis)
- Nail-fold inflammation (paronychia)
- Decreased appetite, nausea, vomiting
Contraindications
- No absolute contraindications in the label
Key interactions
- P-glycoprotein inhibitors (e.g. ritonavir, verapamil, ketoconazole)
- Raise afatinib exposure and toxicity.
- P-glycoprotein inducers (e.g. rifampicin, carbamazepine, St John's wort)
- Lower afatinib exposure.
What is monitored
- Stool frequency and hydration; kidney function and electrolytes if diarrhoea
- Skin and nails
- Liver tests
- New cough or breathlessness
- Eye pain or redness
Administration and safety
- Oral; swallowed whole at about the same time each day.
- Check the name carefully: kinase inhibitors with similar «-tinib» names are not interchangeable.
- Taken on an empty stomach: at least one hour before or two hours after food.
Pregnancy and breastfeeding
Can harm the fetus; effective contraception is used and breastfeeding is avoided.
Nursing care
- Make sure an antidiarrhoeal is available and the patient knows when to use it and when to call.
- Check hydration, weight and kidney function if diarrhoea persists.
- Inspect skin, mouth and nail folds; advise gentle skin care and sun protection.
- Teaching: report severe diarrhoea, blistering rash, new breathlessness or eye pain; use contraception.
Pharmacokinetics
- Absorption
- Oral; taken at least one hour before or two hours after a meal.
- Distribution
- Highly bound to plasma proteins.
- Metabolism
- Little enzymatic metabolism; it forms covalent adducts with proteins. It is a P-glycoprotein substrate.
- Elimination
- Mainly in the faeces.
- Half-life
- About 37 hours.
Test yourself
Think of the answer, then tap the question to see it.
How does afatinib's binding differ from erlotinib's?
Afatinib binds covalently and irreversibly (and also blocks HER2 and HER4); erlotinib binds reversibly.
Which transporter's inhibitors raise afatinib levels?
P-glycoprotein.
Which common afatinib effect can lead to kidney failure?
Severe diarrhoea with dehydration.
Connections
← Back to the class: Kinase inhibitors (targeted oncology)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - AFATINIB- afatinib tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.