Vizimpro Dacomitinib Tablets

1. Indications and Usage
First-Line Treatment of Non-Small Cell Lung Cancer (NSCLC):
Indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.
Note: Patients should have their tumor tested for EGFR mutations using an FDA-approved test.
2. Dosage and Administration
Recommended Dosage:
Adults: 45 mg orally once daily.
Administration Instructions:
Administer orally without regard to food.
Swallow tablets whole; do not crush, break, or chew.
Dose Modifications:
First Dose Reduction: Reduce to 30 mg once daily.
Second Dose Reduction: Reduce to 15 mg once daily.
Dose reductions are recommended based on individual safety and tolerability, particularly for severe diarrhea, skin toxicity, or interstitial lung disease (ILD).
3. Mechanism of Action
Irreversible ErbB Family Blocker:
Dacomitinib is a small molecule, irreversible tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptor (HER1/EGFR), HER2, and HER4.
Physiological Effect:
It binds covalently to the catalytic domains of HER receptors, blocking downstream signaling pathways (such as Ras-Raf-MAPK, PLCgamma-PKC-NFkB, and PI3K/AKT) that regulate tumor cell proliferation and survival.
4. Safety and Warnings
Interstitial Lung Disease (ILD):
Fatal and severe ILD has been observed. Withhold Dacomitinib in patients with suspected ILD and discontinue permanently if ILD is confirmed.
Diarrhea:
Severe diarrhea can occur. Withhold treatment for ≥Grade 2 diarrhea and initiate anti-diarrheal therapy (e.g., loperamide) promptly.
Skin Toxicity:
Severe skin toxicity (e.g., rash, acneiform dermatitis, paronychia) is common. Withhold treatment for persistent Grade 2 or any Grade 3/4 skin toxicity.
Embryo-Fetal Toxicity:
Based on its mechanism of action and animal data, Dacomitinib can cause fetal harm.
5. Adverse Reactions
Most Common:
Diarrhea, rash, paronychia, stomatitis (oral mucositis), decreased appetite, dry skin, weight loss, alopecia, cough, and pruritus.
Laboratory Abnormalities:
Decreased albumin, lymphopenia, anemia, increased ALT, increased AST, increased blood glucose, and hypomagnesemia.
6. Drug Interactions
Proton Pump Inhibitors (PPIs):
Concomitant use of PPIs may decrease the solubility of Dacomitinib and reduce its bioavailability. Avoid co-administration.
CYP2D6 Substrates:
Dacomitinib is primarily metabolized by CYP2D6. Concomitant use with CYP2D6 substrates may increase the concentration of the substrate, potentially leading to toxicity.
7. Pharmaceutical Information
Chemical Name:
(2E)-N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl]-4-(piperidin-1-yl)but-2-enamide