I. Full Name

Chinese Generic Name: Dacomitinib Tablets

English Generic Name: Dacomitinib

English Trade Names: Vizimpro, Duozerun, DAKEDX

Specifications: 15 mg × 30 tablets/box; 45 mg × 30 tablets/box

Drug Category: Second-generation irreversible EGFR tyrosine kinase inhibitor (TKI)

Manufacturer: Bigbear Pharmaceutical Laos

Drug Approval Numbers: 06 L 1357/25 / 06L 1360/25

II. Composition

Active Ingredient: Dacomitinib (monohydrate)

Chemical Name: (2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}-4-(piperidin-1-yl)but-2-enamide monohydrate

Molecular Formula: $\boldsymbol{C_{24}H_{25}ClFN_5O_2·H_2O}$

Molecular Weight: 487.95

Excipients: Microcrystalline cellulose, lactose, sodium starch glycolate, magnesium stearate, blue film coating premix

III. Description

Film-coated tablets; white or off-white in color after removal of the coating.

IV. Indications

Indicated as monotherapy for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletion mutations or exon 21 L858R substitution mutations.

Use of this medication requires confirmation of positive status for the aforementioned mutations via a validated genetic testing method.

V. Dosage and Administration

1. Recommended Dosage

45 mg, orally, once daily, taken at a fixed time each day. It may be taken with or without food. The tablet should be swallowed whole; do not break or crush it. Continue treatment until disease progression or until intolerable toxicity occurs.

2. Management of Missed Doses or Vomiting

If vomiting occurs after taking the medication, or if a dose is missed, do not take an additional dose to make up for it, and do not take a double dose. Simply resume the regular dosing schedule at the next scheduled time. 3. Dose Adjustment for Adverse Reactions (Stepwise)

Initial Dose: 45 mg/day

First Dose Reduction: 30 mg/day

Second Dose Reduction: 15 mg/day

If 15 mg remains intolerable, permanently discontinue the drug.

4. Adjustments for Specific Adverse Reactions

Interstitial Lung Disease (ILD): Permanently discontinue the drug.

Grade 3 or Higher Diarrhea or Skin Toxicity: Temporarily suspend treatment; once resolved to Grade ≤2, resume treatment at a reduced dose (stepwise reduction).

Severe Mucositis or Nail Toxicity: Temporarily suspend treatment, then resume at a reduced maintenance dose.

VI. Adverse Reactions

Common (≥20%)

Diarrhea (87%), Nail Disorders (62%), Rash/Acne (49%), Oral Mucositis (44%); followed by dry skin, pruritus, paronychia, decreased appetite, fatigue, alopecia, and weight loss.

Serious Adverse Reactions

Severe diarrhea with dehydration, severe skin toxicity, infected paronychia, interstitial lung disease, and abnormal liver function.

VII. Contraindications

Contraindicated in patients with a known hypersensitivity to dacomitinib or to any of the excipients.

VIII. Precautions

1. Management of Diarrhea: Have antidiarrheal medications (e.g., loperamide) readily available during the early stages of treatment. For Grade 3 or higher diarrhea, immediately suspend treatment and intervene to prevent dehydration and electrolyte disturbances.

2. Skin Toxicity: Maintain comprehensive sun protection and moisturizing care throughout the treatment course. For severe rash or paronychia, apply topical anti-inflammatory and anti-infective agents; suspend treatment or reduce the dose if necessary.

3. Interstitial Lung Disease (ILD): If dry cough, chest tightness, shortness of breath, or hypoxia occurs during treatment, immediately suspend the drug and conduct an evaluation. If ILD is confirmed, permanently discontinue the drug.

4. Drug Interactions

Concomitant Use Prohibited: Proton Pump Inhibitors (PPIs, e.g., omeprazole), as they significantly reduce drug absorption and efficacy.

Acceptable Alternatives: Antacids or H2 receptor antagonists (administer at least 6 to 10 hours apart from this medication).

Use with Caution: Substrates of CYP2D6; this medication may increase their plasma concentrations, thereby increasing the risk of toxicity. 5. Hepatic and Renal Function: No dose adjustment is required for mild to moderate hepatic or renal impairment; due to insufficient data regarding severe impairment, use is not recommended.

6. Reproductive Safety: Men and women of childbearing potential must practice strict contraception during treatment and for at least 17 weeks after discontinuing the medication; use is contraindicated in pregnant and breastfeeding women.

IX. Pharmacology and Toxicology

Mechanism of Action

A second-generation irreversible pan-HER inhibitor that covalently binds to the kinase domains of EGFR (HER1), HER2, and HER4. It permanently blocks kinase activation and inhibits downstream proliferative signaling. Compared to first-generation agents, it exhibits stronger binding affinity, covers a broader range of targets, and offers a longer duration of efficacy before resistance develops; it demonstrates potent activity against both 19del and L858R mutations.

Pharmacokinetics

Well absorbed following oral administration, with a time to maximum concentration (Tmax) of approximately 6 hours. It undergoes extensive tissue distribution and is primarily metabolized by the liver; with a half-life of 70 hours, its prolonged half-life facilitates the achievement of a sustained steady-state concentration. Excretion occurs primarily via feces, with only a minor amount cleared renally.

X. Storage

Keep tightly sealed. Store in a dry place below 25°C, protected from light and moisture. Keep out of reach of children.

XI. Overdosage

There is no specific antidote. Symptoms of overdose primarily manifest as severe diarrhea, dermatological toxicity, and gastrointestinal reactions. Management focuses on drug discontinuation, anti-diarrheal treatment, fluid replacement, and general symptomatic supportive care.

[Manufacturer Introduction]

Daxiong Pharmaceutical is one of the officially recognized chemical pharmaceutical enterprises in Laos. Following a comprehensive two-year site selection process—conducted in the presence of investors and accompanied by the Minister of Health of Laos—the factory was ultimately established in the national capital, Vientiane. Preparations for the facility began in 2020, culminating in the factory's completion in 2021. The parent company invested substantial capital to implement industrial upgrades, establishing production workshops that meet advanced international manufacturing standards. Furthermore, the company has made significant contributions toward alleviating the shortage of medical supplies and healthcare resources within Laos. Over the past two years, Daxiong Pharmaceutical has maintained a steadfast commitment to innovation and prudent management, achieving steady growth and continuous expansion of its business scope. The company has consistently delivered excellent performance results, with its key economic indicators consistently ranking at the forefront of the domestic pharmaceutical industry in Laos. This marks the beginning of a new chapter for Daxiong Pharmaceutical as it sets out to build a leading domestic and world-class modern pharmaceutical group.