Venex 100 VENETOCLAX 100mg

[Product Name] Venetoclax Tablets

[Active Ingredient] Venetoclax

[Manufacturer] Drug International Pharma Ltd

[Indications]

1. Second-line treatment for Chronic Lymphocytic Leukemia (CLL) with 17p deletion;

2. Second-line treatment for Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) in combination with rituximab;

3. First-line treatment for Acute Myeloid Leukemia (AML) in patients ineligible for standard induction therapy, in combination with azacitidine, decitabine, or cytarabine.

[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 Chronic Lymphocytic Leukemia (CLL) cells and Acute Myeloid Leukemia (AML) cells. BCL-2 mediates tumor cell survival and is associated with chemotherapy resistance. Venetoclax directly binds to the BCL-2 protein, displacing pro-apoptotic proteins and restoring the apoptotic process.

[Product Specifications] 100 mg × 120 Tablets

[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 (AML):

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 agent. 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 daily.

Day 3: 400 mg once daily.

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

Venetoclax in combination with low-dose cytarabine: Day 4 and thereafter: 600 mg daily, 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, 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 7 consecutive days after the patient has been receiving venetoclax at a daily dose of 400 mg.

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 treatment until disease progression, unacceptable toxicity, or until an allogeneic stem cell transplant is performed.

Venetoclax in combination with ibrutinib: Note: Venetoclax administration should begin 4 weeks after the initiation of ibrutinib monotherapy to mitigate the risk of Tumor Lysis Syndrome. Initial dosing schedule: 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 complete remission is not achieved, the daily Venetoclax dose may be increased to 800 mg once daily after Week 16.

**Product Specifications**

**Product Name:** Venetoclax Venex 100 (VENETOCLAX) 100 mg × 120 Tablets/Box

**Common Name:** Venetoclax Tablets

**Active Ingredient:** Venetoclax

**Dosage Form:** Tablets

**Specification:** 120 tablets/box

**Manufacturer:** Drug International Pharma Ltd

**Indications:**

1. Second-line treatment for Chronic Lymphocytic Leukemia (CLL) with chromosome 17p deletion;

2. Second-line treatment for Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) in combination with Rituximab;

3. First-line treatment for Acute Myeloid Leukemia (AML) in patients who are ineligible for standard induction chemotherapy, in combination with Azacitidine, Decitabine, or Cytarabine.

**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 (AML):**

**Adults aged ≥75 years or those with comorbidities:** Oral administration. Note: Begin administration of Azacitidine, Decitabine, or low-dose Cytarabine on Day 1. The Venetoclax dosage depends on the accompanying chemotherapy agent. 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, until disease progression or unacceptable toxicity occurs.

Venetoclax in combination with low-dose cytarabine: Day 4 and thereafter: 600 mg once daily, 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 administration begins on Day 1 of Cycle 1; Venetoclax administration begins on Day 22 of Cycle 1, following the 5-week dose escalation schedule for CLL/SLL described above; the dose escalation phase will be completed by the end of Cycle 2. Cycle 3 (Day 1 and thereafter): 400 mg once daily, continuing 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; continue Venetoclax treatment from Day 1 of rituximab administration (Cycle 1) for up to 24 months, until disease progression or unacceptable toxicity occurs. Rituximab administration should begin after the patient has received Venetoclax at the daily dose of 400 mg for 7 consecutive days. 3. Relapsed/Refractory Mantle Cell Lymphoma:

Venetoclax Monotherapy: Oral administration

Week 1: 20 mg daily

Week 2: 50 mg daily

Week 3: 100 mg daily

Week 4: 200 mg daily

Week 5: 400 mg daily

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

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