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Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.


( a-FA-ti-nib )
Exceptional Access Program
  • AFAtinib - For first-line monotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC), according to specific criteria
Other Name(s): Giotrif®
Appearance: tablet in various strengths and colours
A - Drug Name



B - Mechanism of Action and Pharmacokinetics

Afatinib is an irreversible inhibitor of the ErbB family of tyrosine kinases, including epidermal growth factor receptor (EGFR), HER2 and HER4. It also inhibits transphosphorylation of HER3. EGFR inhibition plays a role in downregulating ErbB signaling, decreasing tumor cell proliferation and vascularization.


Afatinib shows non-linear PK, with exposure increasing slightly more than proportional between 20 mg to 50 mg doses.

Peak plasma levels 2-5 hours
Time to reach steady state 8 days, with 2.8x accumulation in exposure at steady state
Effects with food

Administration following a high-fat meal decreased afatinib exposure by 50%. When food was consumed 3 hrs before or 1 hr after the dose, exposure decreased on average by 26%.




Afatinib is equally distributed into most tissues and covalently binds to albumin and hemoglobin. It accumulates in the retina and skin.

PPB 95%
Cross blood brain barrier? Low with single oral dosing, but accumulation occurs with repeat dosing.

Afatinib undergoes negligible enzymatic metabolism. Metabolized through Michael addition reactions resulting in adduct formation to proteins or small nucleophilic molecules.

Main enzymes involved

P-gp, BCRP

Inactive metabolites



Mainly excreted as parent drug

Half-life 37 hours (terminal, steady state)
Feces 85%
Urine 4%
C - Indications and Status
Health Canada Approvals:

  • Non-small cell lung cancer (NSCLC) 

Refer to the product monograph for a full list and details of approved indications.

D - Adverse Effects

Emetogenic Potential:  

Minimal – No routine prophylaxis; PRN recommended

Extravasation Potential:   Not applicable

The following table lists adverse effects that occurred in ≥ 10% of patients treated with afatinib in a pivotal phase III trial comparing afatinib to pemetrexed/cisplatin in patients with EGFR mutation positive metastatic adenocarcinoma of the lung. It also includes severe, life-threatening and post-marketing adverse effects from other sources.

Cardiovascular Cardiotoxicity (<1%) (6% LVEF decrease of >20%) E  D
Hypertension (2%) E
Venous thromboembolism (<1%) E
Dermatological Alopecia (13%) D
Dry skin (31%) E
Hand-foot syndrome (7%) (1% severe) E
Paronychia (58%) (11% severe) E
Rash, pruritus (71%) (severe 14%) E
Stevens-Johnson syndrome (rare) E
Toxic epidermal necrolysis (rare) E
Gastrointestinal Anorexia, weight loss (29%) E
Constipation (13%) E
Diarrhea (96%) (severe 15%) E
Dyspepsia (4%) E
GI perforation (<1%) E
Mucositis (71%) (severe 9%) E
Nausea, vomiting (25%) E
Hematological Myelosuppression (2%) E
Hepatobiliary ↑ LFTs (11%) (may be severe) E
Pancreatitis (<1%) E
Infection Infection (14%) (including herpes zoster, rarely sepsis) E
Metabolic / Endocrine Abnormal electrolyte(s) (11%) (hypokalemia) E
Musculoskeletal Musculoskeletal pain (14%) E
Nervous System Dizziness (11%) E
Dysgeusia (7%) E
Headache (14%) E
Insomnia (15%) E
Ophthalmic Cataract (1%) (or blurred vision) E  D
Conjunctivitis (11%) E
Keratitis (2%) E
Renal Proteinuria (1%) E
Renal failure (4%) E
Respiratory Cough (15%) E
Epistaxis (17%) E
Other (11%) - Rhinorrhea E
Pneumonitis (1%) (may be severe) E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

The most common side effects for Afatinib include diarrhea, mucositis, rash, pruritus, paronychia, dry skin, anorexia, weight loss, nausea, vomiting, epistaxis, cough and insomnia.

Decreases in left-ventricular ejection fraction (LVEF) were observed in the afatinib arm of the pivotal trial, including decrease of > 20% from baseline or lower than the institution's lower limit of normal.

Severe diarrhea resulting in dehydration, hypokalemia, renal insufficiency and/or death has been reported. Diarrhea appears within the first 2 weeks of treatment, while severe cases occurred within the first 6 weeks of treatment. Patients should be adequately educated on early management and should have a sufficient supply of loperamide. Patients should avoid lactose-containing products or foods that aggravate diarrhea. Ensure hydration and electrolyte replacement is maintained if diarrhea occurs.

Gastrointestinal perforation, including fatal cases, has been rarely reported with afatinib. Patients receiving concomitant medications such as corticosteroids, NSAIDs, or anti-angiogenic agents may be at increased risk. Older patients or those with an underlying history of gastrointestinal ulceration, diverticular disease, or bowel metastases may also be at increased risk of perforation.

Keratitis has been reported with afatinib. Patients with acute or worsening ocular symptoms  (e.g. eye inflammation, lacrimation, light sensitivity, blurred vision, or eye pain) should be referred promptly to an ophthalmologist. Patients should avoid the use of contact lenses during treatment, given an increased risk of keratitis.

Rash generally manifests itself as a mild to moderate erythematous and acneiform rash that may worsen with sun exposure. Patients should protect themselves from the sun. Stevens-Johnson syndrome and toxic epidermal necrolysis have also been reported rarely.

Paronychia is a common side effect. Patients should avoid trauma to nails, finger tips, and chemicals such as soaps, detergents and nail products. Topical antibiotics/antiseptics and/or steroids may be used to treat mild paronychia. For moderate to severe cases, topical or systemic antibiotics and/or steroids as well as periodic silver nitrate application may be beneficial.

E - Dosing

Refer to protocol by which patient is being treated.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

In patients with adenocarcinoma of the lung, EGFR mutation-positive status must be confirmed by a validated test before treatment.

  • Safety and efficacy have not been established in patients with EGFR mutations other than exon 19-deletions (DEL19) and the exon 21 L858R point mutation.
  • Evidence for activity in EGFR TKI naïve patients with uncommon EGFR mutations including the T790M is limited.

Patients must be adequately educated about the management of diarrhea and provided with loperamide when starting afatinib.

Since sunlight can exacerbate skin rash reactions, patients should be advised to avoid the sun or use adequate sun protection.


Oral: 40 mg/day



Dosage with Toxicity:

Dose Level Afatinib Dose (mg/day)
0 40
-1 30
-2 20
-3 Discontinue

Do not re-escalate previously reduced doses.


Refer to H – Interactions section for dosing recommendations when co-administered with P-gp inhibitors or inducers.

Note: The U.S. Prescribing Information suggests reducing afatinib dose by 10mg with P-gp inhibitors and monitoring for toxicity, and increasing afatinib dose by 10mg (as tolerated)
when used with chronic concomitant P-gp inducer therapy. Then, reducing afatinib back to the original dose 2 to 3 days after discontinuing the P-gp inducer.

Table A: Dose Modifications for Toxicity Other than Diarrhea

Toxicity Grade
Grade 1 or 2
Maintain same dose
Prolonged (≥ 7 days) or intolerable grade 2 (including rash, nausea, vomiting and renal impairment) despite adequate symptomatic management**
Grade 3 or 4**
Hold until ≤ grade 1 then restart at ↓ 1 dose level

For skin reactions, consider referral to a specialist.

Hold and refer to ophthalmologist; consider discontinuation
Interstitial Lung Disease
Hold; investigate and treat patient appropriately. Discontinue if confirmed.
LVEF below institution’s lower limit of normal
Cardiac signs and symptoms
Hold and refer to cardiologist; consider discontinuation
Severe hepatic impairment during treatment Discontinue
Gastrointestinal perforation
Bullous, blistering or exfoliating skin conditions, suspected toxic epidermal necrolysis or Stevens-Johnson syndrome

*Permanently discontinue afatinib for any toxicity not recovered to ≤ grade 1 within 14 days or if cannot tolerate 20 mg/day.

**Consider holding afatinib for worsening hepatic function; discontinue if severe hepatic impairment

Table B: Management of Diarrhea

Patients should have an adequate supply of loperamide readily available at the start of and during treatment.

Diarrhea Grade
Take 4mg (2 tablets) of loperamide immediately, followed by 2mg (1 tablet) with every loose bowel movement up to maximum daily dose of 20mg (10 tablets).  Continue until resolved for ≥ 12 hours.
Give oral hydration (1.5L/m2/day plus equivalent of actual fluid loss) and electrolytes especially for ≥ grade 2.
Hospitalize for IV fluids if patients becomes dehydrated.
Avoid lactose containing products.
Grade 1
Grade 2 < 48 hrs
Maintain same afatinib dose.
Grade 2 lasting  ≥ 48 hours despite adequate anti-diarrheal treatment
Grade 3
Hold afatinib until grade ≤ 1 then restart at ↓ 1 dose level. 
Discontinue if not recovered to ≤ grade 1 within 14 days.
Grade 4

Dosage with Hepatic Impairment:

Similar exposure was observed in single-dose study in normal hepatic function versus mild/moderate hepatic impairment.

Hepatic Impairment
Afatinib Starting Dose / Action
Mild (Child Pugh A)
No dose adjustment required. Monitor closely for toxicity.
Moderate (Child Pugh B)
Severe (Child Pugh C)
Do not treat

Dosage with Renal Impairment:

Higher exposure of afatinib was observed in renal impairment, which may increase the risk of developing adverse events. Monitor patients closely for toxicities.

CrCl (mL/min) Afatinib Starting Dose
≥ 60 No adjustment required

No adjustment required; monitor for adverse reactions

15-29 30 mg daily
< 15 or on dialysis Do not treat (not studied) 

Dosage in the elderly:

No dose adjustment required. Elderly patients are more likely to experience severe adverse events, especially diarrhea. Monitor these patients closely for toxicities.

Dosage based on gender:

Higher exposure was observed in female patients as well as patients with lower body weight, which may increase the risk of developing adverse events. Monitor closely for toxicities.

Dosage based on ethnicity:

Population pharmacokinetic analysis suggests that race does not have a clinically important effect on afatinib exposure.


The safety and efficacy of afatinib has not been established in the pediatric population.

F - Administration Guidelines
  • Tablets should be swallowed whole with a glass of water and not crushed or chewed.
  • Afatinib should be taken on an empty stomach, at least 1 hour before or 3 hours after eating.
  • If a dose is missed, afatinib should be taken as soon as it is remembered. If there are less than 8 hours until the next scheduled dose, patients should skip the missed dose and take the next one as scheduled.
  • If vomiting occurs after taking the dose, patients should not take a replacement tablet. The next dose should be taken at its scheduled time.
  • Patients should have an adequate supply of loperamide readily available at the start of, and throughout therapy.
  • Store at 15 - 30oC.
  • Blister card should be stored in the original package away from moisture and light;
  • Only one pouch should be opened at a time.  All the tablets in a blister card should be consumed, before opening a new one.
G - Special Precautions

  • Patients who have a hypersensitivity to this drug or any of its components

Other Warnings/Precautions:

  • Afatinib is not recommended for patients with:
    • Significant or recent gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption or any other relevant disorder).
    • A history of interstitial lung disease
    • Severe hepatic or renal impairment
    • HER-2 positive metastatic breast cancer, in combination with vinorelbine, as increased adverse effects and increased mortality have been reported.
    • With hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption as afatinib tablets contains lactose.
  • Use with caution in patients with:
    • Abnormal LVEF or those with significant cardiac history as afatinib has not been studied in these patient populations.
    • A history of keratitis, ulcerative keratitis, severe dry eye or those who use contact lenses.
  • Blurred vision and keratitis have been observed; caution is required when driving or operating machinery.

Other Drug Properties:

  • Carcinogenicity: Unknown
  • Phototoxicity: Probable
    • Patients should be advised to avoid sun exposure or wear sufficient sun protection.

Pregnancy and Lactation:
  • Mutagenicity: No
  • Genotoxicity: No
  • Embryotoxicity: Yes

    Afatinib is not recommended for use in pregnancy.  Adequate contraception should be used by patients and their partners during treatment, and for at least 2 weeks after the last dose.

  • Fetotoxicity: Yes
  • Breastfeeding:

    Excretion into breast milk documented in animals.

    Breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose.

  • Fertility effects: Probable
H - Interactions

Drug-drug interactions due to inhibition or induction of CYP enzymes or UGT1A1 by concomitant medications are unlikely.

Although afatinib is a moderate inhibitor of Pgp in vitro, clinical data suggest the drug is unlikely to affect other Pgp substrates.

Smoking and alcohol consumption had no significant effects on afatinib pharmacokinetics, while food significantly decreased drug exposure (see Pharmacokinetics).

P-glycoprotein inhibitors (i.e. quinidine, verapamil, cyclosporine, ritonavir) or BCRP inhibitors (i.e. ritonavir) ↑ afatinib exposure (up to 48% observed when P-gp/BCRP inhibitor given before afatinib) ↓ metabolism of afatinib Avoid strong inhibitors if possible. If concomitant use is unavoidable, monitor for toxicity. Consider reducing afatinib dose if combination is not tolerated (See Dosing section).
P-glycoprotein inducers (i.e. rifampin) ↓ afatinib exposure (up to 34% observed) ↑ metabolism of afatinib Avoid strong inducers. Consider adjusting afatinib dose for patients who require chronic therapy with a P-glycoprotein inducer (See Dosing section).
BCRP substrates (i.e. topotecan, rosuvastatin, sulfasalazine) ↑ exposure of BCRP substrates (theoretical) afatinib is a BCRP inhibitor Caution
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Monitor Type Monitor Frequency

Liver function tests

Baseline and at each visit; more frequently in patients with hepatic impairment

Renal function tests and electrolytes (especially in patients at high risk of dehydration)

Baseline and at each visit

LVEF for patients with cardiac risk factors or conditions that can affect LVEF.

Baseline and as clinically indicated

Clinical toxicity assessment of skin and nails, diarrhea, mucositis and other GI, respiratory, ophthalmic and cardiac effects and hypersensitivity/immune reactions

At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Supplementary Public Funding

Exceptional Access Program (EAP Website)

  • AFAtinib - For first-line monotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC), according to specific criteria ()

K - References

Dungo RT, Keating DM. Afatinib: first global approval. Drugs (2013) 73:1503–1515.

Prescribing Information: Gilotrif® (afatinib). Boehringer Ingelheim Pharmaceuticals, Inc. October 2019.

Product Monograph: Giotrif ® (afatinib dimaleate). Boehringer Ingelheim (Canada) Ltd., June 2019.

Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013.

Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol 2015;16(8):897-907.

Yap TA, Popat S. The role of afatinib in the management of non-small cell lung carcinoma. Expert Opin Drug Metab Toxicol 2013; 11:1529-1539.

April 2024 Updated pregnancy/breastfeeding section

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.