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.
AFAT
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
First-line monotherapy for patients with advanced or metastatic EGFR-positive NSCLC. Not funded for patients with disease progression on prior EGFR TKI therapy, or maintenance therapy for NSCLC (see EAP criteria for details).
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.
AFAtinib
Exceptional Access Program
(AFAtinib - For first-line monotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC), according to specific criteria)
(EAP Website)
Minimal – No routine prophylaxis; PRN recommended
Other Supportive Care:
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.
Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
Dose Levels
| Dose Level | Afatinib Dose (mg/day) |
| 0 | 40 |
| -1 | 30 |
| -2 | 20 |
| -3 | Discontinue |
Do not re-escalate previously reduced doses.
Refer to G - Interactions section for dosing recommendations when co-administered with P-gp inhibitors or inducers.
Table A: Dose Modifications for Toxicity Other than Diarrhea
|
Toxicity Grade
|
Action*
|
|
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**
Or Grade 3 or 4**
|
Hold until ≤ grade 1 then restart at ↓ 1 dose level
For skin reactions, consider referral to a specialist. |
|
Keratitis
|
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
Or
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, as well as 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
|
Action
|
|
Any
|
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
or
Grade 2 < 48 hrs
|
Maintain same afatinib dose.
|
|
Grade 2 lasting ≥ 48 hours despite adequate anti-diarrheal treatment
or
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
|
Discontinue
|
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
|
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 |
| 30-59 |
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.
Refer to afatinib drug monograph(s) for additional details of adverse effects
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to afatinib drug monograph(s) for additional details
-
Avoid concomitant use with strong P-glycoprotein (P-gp) inhibitors as they may increase afatinib exposure. If concomitant use is unavoidable, monitor for toxicity. Consider reducing afatinib dose if combination is not tolerated.*
-
Avoid concomitant use with strong P-gp inducers as they may decrease afatinib exposure. May consider afatinib dose adjustment for patients requiring chronic therapy with a P-gp inducer.**
*The US Prescribing Information suggests reducing afatinib dose by 10mg and monitoring for toxicity.
**The US Prescribing Information suggests increasing afatinib dose by 10 mg, 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.
Refer to afatinib drug monograph(s) for additional details
Administration:
-
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.
-
Stored 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.
Contraindications:
- Patients who have a hypersensitivity to this drug or any of its components.
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
- 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.
Pregnancy/Lactation:
- Afatinib is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 2 weeks after the last dose.
- Breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose.
- Fertility effects: Probable
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
-
Liver function tests; baseline and at each visit, more frequently in patients with hepatic impairment
-
Renal function tests and electrolytes; baseline and at each visit (especially in patients at high risk of dehydration)
-
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, cardiac effects and hypersensitivity/immune reactions; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Afatinib drug monograph, Ontario Health (Cancer Care Ontario).
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;31(27):3327-34. 3.
Soria JC, Felip E, Cobo M, et al.; LUX-Lung 8 Investigators. 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 Aug;16(8):897-907.
Yang JC, Shih JY, Su WC, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol 2012;13(5):539-48.
June 2022 Updated Dose Modifications, Adverse Effects, Interactions, Drug Administration and Special Precautions and Recommended Clinical Monitoring sections
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. 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, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
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.