Venetoclax is indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with chromosome 17p deletion.

Venetoclax instructions

Product Name: LuciVenet

Manufacturer: Lucius Pharmaceuticals

Chinese name: Venetoclax

English name: Venetoclax

Drug approval number: 09 L 1009/23

 

【Summary】

Venetoclax is a selective and 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 like BIM, triggering mitochondrial outer membrane permeabilization and activation of caspases. In nonclinical studies, venetoclax has shown cytotoxic activity against tumor cells that overexpress BCL-2.

 

【Indications】

Indicated for patients with chromosome 17p deletion or relapsed/refractory chronic lymphocytic leukemia (CLL).

 

【Specification】

100 mg/tablet, 120 tablets/box.

 

【Storage】

Store at 20°C to 25°C (68°C to 77°F); short-distance transport is permitted at a temperature range of 15 to 30°C (59–86°F).

 

【Usage and Dosage】

The recommended dose of venetoclax is to take the drug in a weekly dose-escalating manner.

Acute myeloid leukemia (AML): 100 mg on the first day; 200 mg on the second day; 400 mg per day starting from the third day.

Chronic lymphocytic leukemia CLL: First week, once a day, 20 mg each time, 1 box of 14 tablets is required. Second week, once a day, 50 mg each time. Third week, once a day, 100 mg each time. Fourth week, once a day, 200 mg each time. From the fifth week onwards, once a day, 400 mg each time.

Until disease progression or unacceptable toxicity. Patients should take the tablet with food and water at approximately the same time each day. The tablet should be swallowed whole without chewing, crushing or breaking before swallowing.

 

【Adverse Reactions】

The most common adverse reactions (≥20%) were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue.

 

【Taboo】

Concomitant use of strong CYP3A inhibitors with venetoclax is contraindicated during initiation and ramp-up.

 

【Notes】

Tumor Lysis Syndrome

Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in previously treated CLL patients with high tumor burden when treated with venetoclax [see ADVERSE REACTIONS.

Venetoclax can cause rapid reductions in tumors and therefore carries a risk for tumor lysis syndrome (TLS) during the initial 5-week ramp-up phase. Changes in blood chemistries consistent with TLS changes requiring prompt management may occur as early as 6 to 8 hours after the first dose of venetoclax and after each dose increase.

The risk of tumor lysis syndrome (TLS) is a continuum based on multiple factors, including tumor burden (see Table 2) and comorbidities. Reduced renal function (CrCl <80 mL/min) further increases the risk. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricemic medications. Monitor blood chemistries and promptly manage abnormalities. Interrupt dosing as needed. Use more intensive measures (intravenous hydration, frequent monitoring, hospitalization) if overall risk increases.

Concomitant use of venetoclax with strong or moderate CYP3A inhibitors and P-gp inhibitors increases venetoclax exposure, potentially increasing the risk of TLS during initiation and ramp-up phases and may require venetoclax dose adjustment.

 

Neutropenia

Grade 3 or 4 neutropenia occurred in 41% (98/240) of patients treated with venetoclax. Monitor complete blood counts throughout the treatment period. Interrupt or reduce dose for severe neutropenia. Consider supportive measures including antimicrobials for signs of infection and use of growth factors.

 

Immunization

Do not administer live attenuated vaccines before, during, or after treatment with venetoclax until B-cell recovery has occurred. The safety and efficacy of immunization with live attenuated vaccines during or after venetoclax treatment have not been studied. Advise patients that vaccination may be less effective.

 

Embryo-fetal toxicity

Based on its mechanism of action and findings in animals, Venetoclax can cause embryo-fetal harm when administered to a pregnant woman. In an embryo-fetal study conducted in mice, administration of venetoclax to pregnant animals at exposures equivalent to those observed in patients at the recommended dose of 400 mg daily resulted in post-implantation loss and decreased fetal weights. There are no adequate and well-controlled studies using Venetoclax in pregnant women. Advise females of reproductive potential to avoid pregnancy during treatment. If Venetoclax is used during pregnancy or the patient becomes pregnant while taking Venetoclax, the patient should be apprised of the potential hazard to the fetus.