Dosage of Afatinib

1 Patient Selection for Non-Resistant EGFR Mutation-Positive Metastatic NSCLC

Select patients for first-line treatment of metastatic NSCLC with Afatinib based on the presence of non-resistant EGFR mutations in tumor specimens.

2 Recommended Dosage

The recommended dosage of Afatinib is 40 mg orally once daily until disease progression or no longer tolerated by the patient.

Take Afatinib at least 1 hour before or 2 hours after a meal.

Do not take a missed dose within 12 hours of the next dose.

3 Dosage Modifications for Adverse Reactions 

Withhold Afatinib for:

Grade* 3 or higher adverse reactions

Diarrhea of Grade 2 persisting for 2 or more consecutive days while taking anti-diarrheal medication.

Cutaneous reactions of Grade 2 that are prolonged (lasting more than 7 days) or intolerable

_{*National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v 3.0}

Resume treatment when the adverse reaction fully resolves, returns to baseline, or improves to Grade 1.

Reinstitute Afatinib at a reduced dose, i.e., 10 mg per day less than the dose at which the adverse reaction occurred.

Permanently discontinue Afatinib for:

Life-threatening bullous, blistering, or exfoliating skin lesions.

Confirmed interstitial lung disease (ILD).

Severe drug-induced hepatic impairment.

Gastrointestinal perforation.

Persistent ulcerative keratitis.

Symptomatic left ventricular dysfunction.

Severe or intolerable adverse reaction occurring at a dose of 20 mg per day.

4 Dosage Modification for Pre-Existing Severe Renal Impairment

The recommended dosage of Afatinib in patients with pre-existing severe renal impairment (estimated  glomerular filtration rate [eGFR* ]15 to 29 mL/min /1.73 m2 ) is 30 mg orally once daily. 

* Use the Modification of Diet in Renal Disease [MDRD] formula to estimate eGFR.

5 Dosage Modifications for Drug Interactions 

P-glycoprotein Inhibitors

Reduce Afatinib daily dose by 10 mg if not tolerated for patients who require therapy with a P-glycoprotein (P-gp) inhibitor. Resume the previous dose after discontinuation of the P-gp inhibitor as tolerated.  

P-glycoprotein Inducers

Increase Afatinib daily dose by 10 mg as tolerated for patients who require chronic therapy with a P-gp inducer. Resume the previous dose 2 to 3 days after discontinuation of the P-gp inducer.

from FDA，2022.04