Instructions for Dacomitinib

1. Generic name: dacomitinib

Product name:Vizimpro/Duozerun

All names: Dacomitinib tablets, Dacomitinib, Dacomitinib, Feixintuo

2. Indications:

Dacomitinib (Dacomitinib) is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, This was found in a test approved by the U.S. Food and Drug Administration (FDA).

3. Usage and dosage:

1. Before treatment: Doctors will select patients for dacomitinib first-line treatment of metastatic non-small cell lung cancer based on the presence of EGFR exon 19 deletion or exon 21 L858R substitution mutation in tumor specimens.

2. Recommended dose: The recommended dose of dacomitinib is 45 mg orally administered once daily until disease progression or unacceptable toxicity occurs. It can be taken with or without food.

3. Dosage adjustment: If a patient experiences adverse reactions while using dacomitinib, the doctor will adjust the drug dose based on the severity of the condition. The first dose will be reduced to 30 mg orally once daily, and the second dose will be reduced to 15 mg orally once daily.

(1) Drug interactions: Avoid concurrent use of proton pump inhibitors (PPIs) when taking dacomitinib. As an alternative to PPIs, use a locally acting antacid or, if using a histamine 2 (H2) receptor antagonist, give dacomitinib at least 6 hours before or at least 10 hours after taking the H2 receptor antagonist.

4. Adverse reactions:

The most common (>20%) adverse reactions in patients receiving dacomitinib were diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, weight loss, alopecia, cough, and pruritus. Laboratory abnormalities included anemia, lymphopenia, hypoalbuminemia, increased ALT, hyperglycemia, increased AST, hypocalcemia, hypokalemia, hyponatremia, increased creatinine, increased alkaline phosphatase, hypomagnesemia, and hyperbilirubinemia.

5. Storage:

Dacomitinib is stored at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F to 86°F).

6. Mechanism of action:

Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2 and HER4) and certain EGFR activating mutations (exon 19 deletion or exon 21 L858R substitution mutation). In vitro, dacomitinib also inhibitsthe activities of DDR1, EPHA6, LCK, DDR2 and MNK1 at clinically relevant concentrations. Dacomitinib demonstrated dose-dependent inhibition of EGFR and HER2 autophosphorylation and tumor growth in mice bearing subcutaneously implanted human tumor xenografts driven by HER family targets, including mutated EGFR. Dacomitinib also demonstrated antitumor activity in orally administered mice bearing intracranial human tumor xenografts driven by EGFR amplification.