Systemic Therapy Program
Search Again


Disease Group

Cancer Type

Document Type

Drug Monographs
Treatment Regimens
Scientific Name:
Brand Name(s):

Drug Monograph


Mechanism of Action

Afatinib covalently binds to the kinase domains of both wild-type and mutated  EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2. 


Oral Absorption:
Peak plasma concentration (Tmax): 2-5 hours.
Taking with food decreases absorption. A high-fat meal decreased Cmax by 50% and AUC0-∞ by 39% relative to fasted conditions.
Time to reach steady-state plasma concentrations: 8 days with 2.8x accumulation in exposure at steady state
PPB: 95%.
Covalent adducts to proteins are the major circulating metabolites of Afatinib and enzymatic metabolism of Afatinib is minimal
Mainly excreted as parent drug.
Excretion primarily via feces (85%) with 4% recovered in the urine.
The elimination half-life of afatinib is 37 hours after repeat dosing in cancer patients.

Side Effects

EARLY ONSET  (days to weeks)
   diarrhea (96%; 15% Grade 3), stomatitis (71%; 9% Grade 3), chelitis(12%)
   rash/dermatitis acneiform 90% (grade 3- 16%); pruritus (21%); dry skin (31%); palmar-plantar erythrodysesthesia syndrome (7%)
   paronychia 58% (grade 3- 11%)
   cystitis (13%)
   decreased appetite (29%)
   epistaxis (17%), rhinorrhea (11%)
   pyrexia (12%)
   conjunctivitis (11%)
   LVEF reduction by 10-20% (25%) or greater than 20% (5.9%)
* pulmonary toxicity/ interstitial lung disease-like adverse reactions (1.3%)
* hepatic failure (>1%)


Approved Indications

Metastatic non-small cell lung cancer (NSCLC- including cytologically proven pleural effusion) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations




Take once daily on an empty stomach (at least 1 hour before or 2 hours after a meal)


• 40 mg orally, once daily
• Do not take a missed dose within 12 hours of the next dose

Dose Adjustment Criteria

P-gp Inhibitors
For patients who require therapy with a P-glycoprotein (P-gp) inhibitor, reduce  Afatinib daily dose by 10 mg if not tolerated. Resume the previous dose after discontinuation of the P-gp inhibitor as tolerated.
P-gp Inducers
For patients who require chronic therapy with a P-gp inducer, increase  Afatinib daily dose by 10 mg as tolerated. Resume the previous dose 2 to 3 days after discontinuation of the P-gp inducer
Permanently discontinue Afatinib for:
• Life-threatening bullous, blistering, or exfoliative skin lesions
• Confirmed interstitial lung disease (ILD)
• Severe drug-induced hepatic impairment 
• Persistent ulcerative keratitis
• Symptomatic left ventricular dysfunction
• Severe or intolerable adverse reaction occurring at a dose of 20 mg per day




Clinical Monitoring

• Liver function tests; baseline and regular
• Renal function tests and electrolytes (especially in patients at high risk of dehydration); baseline and regular
• LVEF for patients with cardiac risk factors; baseline and regular
• Clinical toxicity assessment of diarrhea, skin and nails, mucositis and other GI, respiratory,  ophthalmic, hypersensitivity/immune reactions; regular
• Grade toxicity using the current NCI­CTCAE (Common Terminology Criteria for Adverse  Events) version

Extravasation Hazard

not applicable

Significant Interactions

• 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 • Drug-drug interactions with compounds that are substrates and/or modulate CYP450 enzyme activity are unlikely

Product Information

Commercial Product Description

Brand Name: Giotrif 40 mg: light blue, film-coated, round, biconvex, bevel-edged tablets debossed with “T40” on one side and the Boehringer Ingelheim company symbol on the other side. 30 mg: dark blue, film-coated, round, biconvex, bevel-edged tablets debossed with “T30” on one side and the Boehringer Ingelheim company symbol on the other side. 20 mg: white to slightly yellowish, film-coated, round, biconvex, bevel-edged tablets debossed with “T20” on one side and the Boehringer Ingelheim company symbol on the other side. Store at room temperature away from direct light and humidity.


Handling Risk Level:
FDA Pregnancy Risk Factor D
• This drug must be handled using precautions outlined in CCNS Policies for Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy and the CCNS Standard for Oral Systemic Therapy for Cancer
• Go to "Additional Information" tab (above) for links to CCNS Policies

Advanced Non Small Cell Lung Cancer
pCODR Recommendations: Afatinib as first-line treatment for pateints with EGFR mutation positive advanced or metastatic adenomacarcinoma of the lung and with an ECOG performace status.  Afatinib may be used in sites where cisplatin-pemetrexed is currently the main treatment option in current use, and maybe used as an alternative treatment to gefitinib - see pCODR website for most current recommendations.  May 2, 2014

Visit the Pan-Canadian Oncology Drug Review website ( for the guidelines on afatinib for advanced non small cell lung cancer.
• Go to "Additional Information" tab (above) for links to pCODR Reviews

Availability & Funding