Dosage Guidelines for Afatinib

As a targeted therapeutic agent, the dosage and administration of afatinib should be individually adjusted based on the patient’s specific condition, body surface area and tolerability. It must be used under the guidance of a physician experienced in antineoplastic therapy.

Recommended Dosage for Adult Patients with Non-Small Cell Lung Cancer

The standard dosage for adult patients with non-small cell lung cancer is 40 mg orally once daily, with continuous administration until disease progression or unacceptable toxicity occurs.

Administration Notes

Afatinib should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal.

The epidermal growth factor receptor (EGFR) mutation status of the patient should be confirmed prior to initiation of treatment.

If a dose is missed, the missed dose should not be taken if the next scheduled dose is due in less than 12 hours.

Dosage Adjustment in Patients with Renal Impairment

Dosage adjustment for patients with renal impairment is determined based on creatinine clearance (CrCl):

No dosage adjustment is required for mild to moderate renal impairment (CrCl ≥30 mL/min).

For severe renal impairment (CrCl 15–29 mL/min), the dosage should be reduced to 30 mg orally once daily.

No data are available in patients with end-stage renal disease (CrCl <15 mL/min) or those requiring dialysis; the dosage should be determined by a physician after comprehensive evaluation.

Dosage Adjustment in Patients with Hepatic Impairment

Dosage adjustment for patients with hepatic impairment is based on the Child-Pugh classification:

No dosage adjustment is required for mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment.

For severe hepatic impairment (Child-Pugh Class C), close monitoring of the patient’s condition is recommended, and prompt dosage adjustment should be made if intolerable adverse reactions occur.

Dosage Adjustment Regimens

(I) Dosage Adjustment Based on Adverse Reactions

Situations Requiring Treatment Interruption

Treatment should be interrupted if adverse events of Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) occur.

Treatment should be interrupted if Grade 2 or higher diarrhea persists for 2 or more days despite the use of antidiarrheal medication.

Treatment should be interrupted if Grade 2 skin reactions persist for more than 7 days or are intolerable to the patient.

Treatment should be interrupted if Grade 2 or higher renal impairment occurs.

Requirements for Resuming Treatment

Treatment may be resumed when adverse reactions resolve completely, return to baseline pretreatment levels, or improve to Grade 1. The dosage should be reduced by 10 mg per day from the dose at which the adverse reaction occurred when resuming treatment.

Situations Requiring Permanent Discontinuation

Permanent discontinuation is required if life-threatening bullous, blistering or exfoliative skin lesions occur.

Permanent discontinuation is required if interstitial lung disease (ILD) is diagnosed.

Permanent discontinuation is required if severe drug-induced hepatic impairment occurs.

Permanent discontinuation is required if persistent ulcerative keratitis occurs.

Permanent discontinuation is required if symptomatic left ventricular dysfunction occurs.

Permanent discontinuation is required if severe or intolerable adverse reactions occur at a daily dosage of 20 mg.

(II) Dosage Adjustment Based on Drug-Drug Interactions

Concomitant Use with P-glycoprotein (P-gp) Inhibitors

If a patient requires concomitant treatment with a P-gp inhibitor and intolerable adverse reactions occur, the daily dosage of afatinib should be reduced by 10 mg. The previous dosage of afatinib may be resumed upon discontinuation of the P-gp inhibitor if tolerated by the patient.

Concomitant Use with P-glycoprotein (P-gp) Inducers

If a patient requires long-term concomitant treatment with a P-gp inducer, the daily dosage of afatinib may be increased by 10 mg if tolerated. The previous dosage of afatinib may be resumed 2–3 days after discontinuation of the P-gp inducer.