Instructions for Venetoclax

1. Name: Venetoclax, Venetoclax, Venetoclax, Venetoclax, Venetoclax, Venetoclax

Product name: Venclexta, Venclyxto

2. Indications:

1. Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): Venetoclax (Venetoclax) is suitable for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

2. Acute myeloid leukemia (AML): Venaclat is suitable for combined treatment with azacitidine, decitabine or low-dose cytarabine Adults 75 years of age or older with newly diagnosed acute myeloid leukemia, or adults with comorbidities that preclude the use of intensive induction chemotherapy.

3. Usage and dosage:

1. Before use: For patients at risk of developing tumor lysis syndrome (TLS), doctors will evaluate specific factors and provide patients with preventive hydration and anti-hyperuricemia treatment before the first dose of venetoclax to reduce the risk of TLS.

2. Recommended dosage:

(1) Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Administration of venetoclax begins with a 5-week ramp-up phase, a 5-week escalating dose regimen designed to gradually reduce tumor burden (tumor reduction) and reduce the risk of tumor lysis syndrome. The daily oral dose is 20 mg in the first week, the daily oral dose is 50 mg in the second week , and the daily oral dose is in the third week pan>100mg, the daily oral dose in the fourth week is 200mg, and the daily oral dose in the fifth week and beyond is 400mg.

1) Monotherapy: The recommended dose of venetoclax is 400 mg once daily after completion of the 5-week escalating dose regimen, and treatment is continued until disease progression or unacceptable toxicity occurs.

2) Combined use with Obinutuzumab: 100mg of Obinutuzumab is taken starting on day 1 of cycle 1, 900mg on day 2, 1000mg on days 8 and 15 and subsequently on day 1 of each 28-day cycle for a total of 6 cycles. On day 22 of cycle 1, start venetoclax according to the 5-week accelerated dosing schedule; After completing the accelerated period on day 28 of cycle 2, continue starting on day 1 of cycle 3Take venetoclax 400 mg orally once daily until the last day of cycle 12.

3) Combined use with Rituximab: Rituximab is started after the patient has completed the 5-week escalating dose regimen of venetoclax and received the recommended dose of 400 mg of venetoclax orally once daily (for a total of 7 days). It is administered on the first day of each 28-day cycle, for a total of 6 cycles. The intravenous dosage in the first cycle is 375 mg/m2, and the intravenous dosage in cycles 2-6 is 500 mg/m2. Beginning on the 1st day of the cycle 1 of Rituximabveneclase 400 mg was taken orally once daily for 24 months.

(2) Acute myeloid leukemia (AML): The recommended doses and increments of venetoclax depend on the combination, following the dosing schedule, including 3-day or 4-day dose escalation, in Start taking it on the 1st day of cycle 1, the oral dose is 100mg, the dose on the second day is 200mg, the oral dose on the third day is 400mg, the daily oral dose on the 4th day and thereafter is 400mg;

Can be used simultaneously at this time: azacitidine 75 mg/m2 intravenously or subcutaneously once daily on days 1-7 of each 28-day cycle; or decitabine 20 mg/m2 intravenously once daily on days 1-5 of each 28-day cycle; or cytarabine 20 mg/m2 subcutaneously once daily on days 1-10 of each 28-day cycle.

3. Dosage adjustment:

For patients with severe hepatic impairment (Child-Pugh class C), reduce the once-daily dose of venetoclax by 50%; monitor these patients more closely for adverse reactions.

4. Combined medication: 2-3 days after discontinuing strong or moderate CYP3A inhibitors or P-gp inhibitors, resume the previous dose of venetoclax.

4. Adverse reactions:

In clinical studies in chronic lymphocytic leukemia/small lymphocytic lymphoma, including monotherapy or combination therapy, the most common adverse reactions (≥20%) with venetoclax were neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper respiratory tract infection, cough, musculoskeletal pain, fatigue, and edema.

In clinical studies of acute myeloid leukemia, including combination therapy, the most common adverse reactions(≥30%) were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, oropharyngeal pain, and hypotension.

5. Storage:

Veneclat may be stored in86°F (30°C) or below in its original container, protected from moisture.

6. Taboo:

Due to the potential for increased risk of tumor lysis syndrome, patients with chronic lymphocytic leukemia/small lymphocytic lymphoma are contraindicated in the initial and accelerated phases of concurrent use of venetoclax and strong CYP3A inhibitors.

7. Mechanism of action:

Venetoclaxis a selective and orally bioavailable small molecule inhibitor of the anti-apoptotic proteinBCL-2. Overexpression of BCL-2 has been demonstrated in chronic lymphocytic leukemia and acute myeloid leukemia cells, where BCL-2 mediates tumor cell survival and is associated with resistance to chemotherapeutic drugs. VeneclaBy directly bindingBCL-2 protein, it replaces pro-apoptotic proteins such as BIM, triggers mitochondrial outer membrane permeabilization and activation of caspases, and helps restore the apoptotic process. In non-clinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells overexpressing BCL-2.

The original drug of Venecla is already on the market in China and can be found in the Category B medical insurance directory, but it is limited to adult patients with acute myeloid leukemia. The price of each box of 100mg*14 tablets may be around RMB 5,000. The Turkish version of Venaclaoriginal drug, specifications100mg*112 tablets, sold overseas, costs around RMB 10,000 per box (the price may fluctuate due to exchange rates), which is even more expensive. There are also cheaper generic drugs for sale, the ingredients of which are basically the same as those of the original drugs. The price of a box of 100mg*120 tablets produced by a Bangladeshi pharmaceutical factory is around RMB 4,000 (the price may fluctuate due to the exchange rate).