I. Drug Name

Generic Name: Dasatinib Tablets

English Name: Dasatinib

Brand Names: Sprycel, Shidasai, Dasanat

Dosage Form: Film-coated tablets

Specification: 20 mg/tablet; 50 mg/tablet; 60 tablets/box

Manufacturer: NATCO PHARMA LTD

II. Indications and Usage

This product is a BCR-ABL1 and SRC family tyrosine kinase inhibitor indicated for the treatment of:

1. Chronic Myeloid Leukemia (CML): Newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) CML in the chronic phase; and adult patients with Ph+ CML in the chronic, accelerated, or blast phase (myeloid or lymphoid) who are resistant or intolerant to prior therapy, including imatinib.

2. Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (ALL): Adult patients with Ph+ ALL who are resistant or intolerant to prior therapy.

III. Dosage and Administration

Recommended Dosage:

CML Chronic Phase (Newly Diagnosed): 100 mg orally once daily.

CML Chronic Phase (Resistant/Intolerant): 140 mg orally once daily.

CML Accelerated Phase/Blast Phase and Ph+ ALL: 140 mg orally once daily.

Administration: Tablets should be swallowed whole; they should not be crushed or split. They may be taken with or without food.

Dose Adjustment: The dose may be escalated or interrupted based on the severity of hematologic and non-hematologic toxicities.

Response to Therapy: Response to therapy should be monitored periodically via cytogenetic and molecular testing.

IV. Contraindications

Patients with hypersensitivity to dasatinib or to any of the excipients.

V. Warnings and Precautions

1. Myelosuppression:

Treatment may cause severe cytopenias, particularly in patients with CML in the accelerated or blast phase, and in patients with Ph+ ALL. Complete blood counts should be monitored weekly for the first two weeks of therapy, then periodically thereafter; dose adjustments or treatment interruptions should be implemented as appropriate.

2. Hemorrhage-Related Events:

Serious hemorrhage-related events may occur. Patients with severe thrombocytopenia are at higher risk. Monitor for signs of bleeding and provide medical intervention if necessary.

3. Fluid Retention:

Pleural effusion is the most common manifestation, which may be accompanied by cough and dyspnea. Pericardial effusion, pulmonary edema, and generalized edema may also occur. Monitor body weight and signs of fluid retention; administer diuretics or short-term corticosteroid therapy as needed. In severe cases, dose reduction or discontinuation of the drug may be required.

4. Pulmonary Arterial Hypertension (PAH):

PAH may develop, manifesting as dyspnea, fatigue, hypoxia, and fluid retention. Upon confirmed diagnosis, the drug must be permanently discontinued; symptoms may be reversible in some patients following discontinuation.

5. QT Interval Prolongation:

The drug may cause prolongation of the QT interval on the electrocardiogram (ECG), carrying a potential risk of developing Torsades de Pointes. Correct hypokalemia and hypomagnesemia prior to initiating treatment, and perform periodic ECG monitoring.

6. Severe Cutaneous Reactions:

Cases of Stevens-Johnson syndrome and erythema multiforme have been reported. If such reactions occur, the drug must be permanently discontinued.

7. Fetal Toxicity:

The drug may cause harm to the fetus. Women and men of reproductive potential should utilize effective contraception during treatment and for a period of time following discontinuation of the drug.

VI. Adverse Reactions

Based on clinical trial data, common adverse reactions (incidence ≥ 20%) include:

Blood and Lymphatic System: Myelosuppression (thrombocytopenia, neutropenia, anemia).

General Disorders: Fluid retention (pleural effusion, peripheral edema), fatigue, pyrexia.

Gastrointestinal System: Diarrhea, nausea, abdominal pain, vomiting.

Musculoskeletal System: Musculoskeletal pain, headache.

Skin and Subcutaneous Tissue: Rash.

Respiratory System: Dyspnea, cough.

Infections: Pneumonia, upper respiratory tract infection.

Other: Hemorrhage, infection.

VII. Drug Interactions

CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, grapefruit juice): These agents increase plasma concentrations of dasatinib, thereby increasing the risk of adverse reactions. Concomitant use should be avoided, or patients should be closely monitored. CYP3A4 Inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, St. John's wort): These agents may significantly reduce dasatinib plasma concentrations, thereby compromising therapeutic efficacy. Consideration should be given to switching to alternative medications that do not interact, or to increasing the dasatinib dosage.

Antacids and Proton Pump Inhibitors: Reduced gastric acidity may decrease the absorption of dasatinib. Concomitant administration with antacids (e.g., aluminum hydroxide) should be avoided; if necessary, a separation of at least 2 hours between doses is recommended. Concomitant use with potent proton pump inhibitors (e.g., omeprazole) should be avoided; consideration may be given to switching to an H2-receptor antagonist (e.g., famotidine), which should be administered at least 2 hours prior to, or 10 hours after, the dasatinib dose.

CYP3A4 Substrates with a Narrow Therapeutic Window (e.g., astemizole, cyclosporine, ergot derivatives, fentanyl, pimozide, quinidine, sirolimus, tacrolimus): Dasatinib may inhibit the metabolism of these agents, leading to increased plasma concentrations and an elevated risk of toxicity; therefore, close monitoring is required.

VIII. Use in Specific Populations

Hepatic Impairment: Patients with hepatic impairment (Child-Pugh Class A, B, or C) may experience increased drug exposure; close monitoring is required, and consideration should be given to reducing the starting dosage.

Renal Impairment: No dosage adjustment is required for patients with mild to moderate renal impairment. Data regarding patients with severe renal impairment or end-stage renal disease are limited; therefore, the drug should be used with caution in these populations.

Pediatric Use: Approved for use in pediatric patients (aged ≥1 year) with Philadelphia chromosome-positive (Ph+) Chronic Myeloid Leukemia (CML) in the chronic phase. Dosage is calculated based on body weight and body surface area.

Geriatric Use: Elderly patients (aged ≥65 years) may be more susceptible to adverse reactions such as fluid retention, dyspnea, fatigue, and bleeding; therefore, close monitoring is required.

IX. Pharmacological Actions

Pharmacological Class: Multi-targeted tyrosine kinase inhibitor.

Mechanism of Action: Potently inhibits the BCR-ABL1 kinase (with greater activity than imatinib) and the SRC-family kinases. It induces apoptosis (programmed cell death) in CML and Ph+ ALL cells by blocking the proliferative signals generated by these abnormal kinases. 10. Storage

Store at room temperature (20°C–25°C).

Keep the medication in its original packaging to protect it from moisture.

Keep this medication out of the reach of children.

Important Note:

This package insert serves as a summary of information and is not a substitute for professional medical advice. Before using Dasatinib, patients must undergo a comprehensive evaluation by a specialist and strictly adhere to the detailed dosing instructions provided by their physician and pharmacist. Regular monitoring and follow-up are mandatory throughout the course of treatment.