Erlotinib
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 reversible EGFR kinase inhibitor for lung cancer with EGFR exon 19 or L858R mutations, and for pancreatic cancer; rash and diarrhoea are typical.
Quick facts
- Group
- Kinase inhibitors (targeted oncology)
- Target
- EGFR tyrosine kinase domain
- Used for
- Advanced pancreatic cancer
- Key effects
- Acne-like rash · Diarrhoea · Loss of appetite
- Monitor
- EGFR mutation test before starting · Skin
- ATC
- L01EB02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows erlotinib in the ATP pocket of the human EGFR kinase domain.
Erlotinib competes with ATP and reversibly inhibits the tyrosine kinase of EGFR, so the receptor cannot autophosphorylate and downstream growth and survival signals stop. It binds the common activating mutations (exon 19 deletion, L858R) more tightly than the normal receptor, which is why lung tumours with these mutations respond best. Tumours escape mainly through the T790M gatekeeper mutation.
- Competes with ATP in the EGFR kinase pocket
- Receptor autophosphorylation is blocked
- Downstream growth signals stop
- Best in exon 19 deletion or L858R tumours
Indications
- Metastatic non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858R mutation. Lung cancer →
- Advanced pancreatic cancer, with gemcitabine. Pancreatic cancer →
Adverse effects
Common
- Acne-like rash
- Diarrhoea
- Loss of appetite, nausea, vomiting
- Fatigue
- Cough and breathlessness
- Dry eyes and eyelash changes
Contraindications
- No absolute contraindications in the label; it is not recommended with platinum chemotherapy
Key interactions
- Strong CYP3A4 inhibitors and inducers
- Inhibitors raise and inducers lower erlotinib levels; avoided when possible.
- Cigarette smoking
- Induces CYP1A2 and lowers erlotinib levels; stopping smoking is encouraged.
- Proton pump inhibitors, H2 blockers and antacids
- Raise gastric pH and reduce absorption; proton pump inhibitors are avoided, the others are separated in time.
- Warfarin
- Raised INR and bleeding; the INR is followed closely.
What is monitored
- EGFR mutation test before starting
- Liver tests and kidney function with electrolytes
- New or worse cough, breathlessness or fever (lung disease)
- Skin, eyes and bowel habit
- INR if on warfarin
Administration and safety
- Oral, on an empty stomach (food raises absorption).
- Proton pump inhibitors are avoided; H2 blockers and antacids are taken hours apart.
- Diarrhoea is treated early to avoid dehydration and kidney injury.
Pregnancy and breastfeeding
Can harm the fetus; effective contraception is used and breastfeeding is avoided.
Nursing care
- Ask about rash, diarrhoea, eye pain or redness and new cough at each visit.
- Check hydration, kidney function and electrolytes if diarrhoea is significant.
- Ask about smoking and review the medicine list for acid reducers and warfarin.
- Teaching: gentle skin care and sun protection, report sudden breathlessness, eye pain or severe diarrhoea; use contraception.
Pharmacokinetics
- Absorption
- Oral; food increases absorption, so it is taken on an empty stomach; high gastric pH reduces it.
- Distribution
- Highly bound to albumin and alpha-1 acid glycoprotein.
- Metabolism
- Liver, mainly CYP3A4 and partly CYP1A2; smoking (CYP1A2 induction) lowers its levels.
- Elimination
- Mainly in the faeces as metabolites.
- Half-life
- About a day and a half.
Test yourself
Think of the answer, then tap the question to see it.
Which EGFR mutations predict response to erlotinib?
Exon 19 deletions and the exon 21 L858R substitution.
Why do smokers have lower erlotinib levels?
Tobacco smoke induces CYP1A2, which helps metabolise erlotinib.
Which resistance mutation usually appears after erlotinib, and which drug covers it?
T790M; osimertinib is active against it.
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 - ERLOTINIB tablet, film coated (DailyMed (U.S. National Library of Medicine), 2022); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.