VECLADX Venetoclax tablets

[Product Name] Venetoclax Tablets

[Other Names] Venetoclax

[English Name] Venetoclax Tablets

[Specification] 0.1g × 112 tablets; 112 tablets per box.

[Manufacturer] Bigbear Pharmaceutical Laos

Venetoclax is a selective, orally bioavailable small-molecule inhibitor of BCL-2, an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells, where it mediates tumor cell survival and is associated with resistance to chemotherapy. Venetoclax helps restore the apoptotic process by directly binding to the BCL-2 protein, displacing pro-apoptotic proteins such as BIM, and triggering mitochondrial outer membrane permeabilization and the activation of caspases. In non-clinical studies, venetoclax has demonstrated cytotoxic activity against tumor cells that overexpress BCL-2.

[Indications]

Venetoclax Tablets are a targeted therapy drug primarily indicated for the following conditions:

1. Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Venetoclax Tablets, in combination with rituximab, are indicated for the treatment of adult patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), with or without the 17p deletion (del 17p). This combination therapy regimen can improve patient response rates and extend patient survival. The 17p deletion is a cytogenetic abnormality associated with a poor prognosis in CLL/SLL patients; Venetoclax acts by targeting the specific biological mechanisms underlying this disease.

For newly diagnosed adult patients with Acute Myeloid Leukemia (AML) who are ineligible for intensive induction chemotherapy, Venetoclax Tablets may be used in combination with azacitidine, decitabine, or low-dose cytarabine. This treatment helps patients achieve better therapeutic outcomes, such as improved rates of complete remission. In the context of AML, Venetoclax primarily functions by inhibiting the anti-apoptotic protein BCL-2, thereby inducing apoptosis in leukemia cells. 2. Acute Myeloid Leukemia (AML)

- Venetoclax tablets, in combination with daunorubicin and cytarabine, are used to treat newly diagnosed adult patients with Acute Myeloid Leukemia (AML); this combination chemotherapy regimen helps to improve treatment response rates and survival rates.

It is important to note that the use of this medication should be conducted under the guidance of a medical professional. A physician will make a comprehensive assessment—based on the patient's specific circumstances, such as age, physical condition, and other comorbidities—to determine whether Venetoclax tablets are appropriate and to establish a specific treatment plan. Furthermore, certain adverse reactions—such as neutropenia, thrombocytopenia, diarrhea, and nausea—may occur during treatment and require close monitoring.

【Mechanism of Action】

Venetoclax exhibits cytotoxic activity in tumor cells that overexpress BCL-2. Venetoclax selectively inhibits the anti-apoptotic protein BCL-2, which is overexpressed in cells associated with Chronic Lymphocytic Leukemia (CLL) and Acute Myeloid Leukemia (AML). BCL-2 mediates tumor cell survival and is associated with chemotherapy resistance. Venetoclax binds directly to the BCL-2 protein, displacing pro-apoptotic proteins and restoring the apoptotic process.

【Side Effects】

Neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, fatigue.

【Dosage and Administration】

Assess the risk of Tumor Lysis Syndrome (TLS); initiate prophylactic hydration and anti-hyperuricemic therapy prior to the first dose of Venetoclax.

1. Newly Diagnosed Acute Myeloid Leukemia:

Adults aged ≥75 years or those with comorbidities: Oral administration. Note: Begin administration of azacitidine, decitabine, or low-dose cytarabine on Day 1. The dosage of Venetoclax depends on the accompanying chemotherapy agents used. Prior to initiating Venetoclax, the leukocyte count should be less than 25,000/mm³; cytoreduction may be required prior to treatment.

Day 1: 100 mg once daily.

Day 2: 200 mg once daily.

Day 3: 400 mg once daily.

Venetoclax in combination with azacitidine or decitabine: Day 4 and thereafter: 400 mg once daily, continued until disease progression or unacceptable toxicity occurs.

Venetoclax in combination with low-dose cytarabine: Day 4 and thereafter: 600 mg once daily, continued until disease progression or unacceptable toxicity occurs.

2. Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL): Oral Administration

Week 1: 20 mg once daily.

Week 2: 50 mg once daily.

Week 3: 100 mg once daily.

Week 4: 200 mg once daily.

Week 5: 400 mg once daily. Venetoclax Monotherapy:

Week 5 and thereafter: 400 mg once daily; continue treatment until disease progression or unacceptable toxicity occurs. Venetoclax in combination with obinutuzumab:

Note: Obinutuzumab is initiated on Day 1 of Cycle 1; Venetoclax is initiated on Day 22 of Cycle 1, following the 5-week ramp-up schedule for CLL/SLL described above; the ramp-up phase is completed by the end of Cycle 2. Cycle 3 (Day 1 and thereafter): 400 mg once daily, continued until the end of Cycle 12. Each cycle consists of 28 days. Venetoclax in combination with rituximab: Week 5 and thereafter: 400 mg once daily; initiated on Day 1 of rituximab administration (Cycle 1) and continued for up to 24 months, or until disease progression or unacceptable toxicity occurs. Rituximab administration should commence after the patient has received venetoclax at a daily dose of 400 mg for 7 consecutive days.

3. Relapsed/Refractory Mantle Cell Lymphoma:

Venetoclax Monotherapy: Oral administration

Week 1: 20 mg once daily

Week 2: 50 mg once daily

Week 3: 100 mg once daily

Week 4: 200 mg once daily

Week 5: 400 mg once daily

Week 6 and thereafter: 800 mg once daily; continue until disease progression, unacceptable toxicity, or until an allogeneic stem cell transplant is performed.

Venetoclax in combination with ibrutinib: Note: Venetoclax administration should begin after 4 weeks of ibrutinib monotherapy to mitigate the risk of Tumor Lysis Syndrome. Initial Dosing: Week 5: 20 mg once daily; followed by Week 6: 50 mg once daily; then Week 7: 100 mg once daily; Week 8: 200 mg once daily; and Week 9 onwards: 400 mg once daily. Continue treatment until disease progression or unacceptable toxicity occurs. If a complete response is not achieved, the once-daily dose of Venetoclax may be increased to 800 mg after Week 16.

[Storage]

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