How it is administered

Venetoclax is administered orally as a tablet. It should be taken once daily with a meal and water, and the tablets must be swallowed whole without chewing, crushing, or breaking them. Venetoclax tablets are available in strengths of 10 mg, 50 mg, and 100 mg. The dosing schedule often involves a gradual increase (ramp-up) over several weeks to reduce the risk of tumor lysis syndrome (TLS), especially in blood cancers like CLL/SLL.

How it works

Venetoclax is a targeted therapy known as a BCL-2 inhibitor. BCL-2 is a protein that helps cancer cells survive by preventing the normal process of cell death (apoptosis). In many blood cancers, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML), BCL-2 is overexpressed, allowing cancer cells to live longer than they should.

Venetoclax works by selectively binding to the BCL-2 protein, blocking its function. This action releases pro-apoptotic proteins, which then trigger the cancer cells to undergo apoptosis. By restoring the cell's ability to self-destruct, venetoclax helps reduce the number of cancer cells in the body. This mechanism is particularly effective in cancers where BCL-2 is a key factor in cell survival.

Who Should take it

Venetoclax is approved for adults with certain blood cancers:

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), either alone or in combination with other medications such as obinutuzumab or rituximab.
• Newly diagnosed acute myeloid leukemia (AML) in adults who are 75 years or older, or who have other health conditions that make them unsuitable for intensive chemotherapy. In AML, venetoclax is used in combination with azacitidine, decitabine, or low-dose cytarabine.

While there is no specific FDA indication for B-Cell Prolymphocytic Leukemia (B-PLL), venetoclax may be considered in some cases based on its mechanism and use in related B-cell malignancies. Always consult your healthcare provider for guidance on your specific diagnosis.

Who should not take it

Venetoclax should not be taken by patients who are starting therapy or in the ramp-up phase for CLL/SLL if they are also taking strong CYP3A inhibitors (such as certain antifungals or antibiotics), as this combination can greatly increase the risk of tumor lysis syndrome (TLS).

Caution is also advised in patients with severe liver impairment, and the medication is not recommended for use in children as its safety and effectiveness have not been established in pediatric patients. Women who are pregnant or breastfeeding should not take venetoclax, as it may harm the fetus or infant. Always inform your healthcare provider of all medications and supplements you are taking to avoid harmful interactions.

Commonly used with

Venetoclax is often used in combination with other medications for blood cancers:

• With obinutuzumab or rituximab for CLL/SLL
• With azacitidine, decitabine, or low-dose cytarabine for AML

These combinations are designed to increase the effectiveness of treatment by attacking cancer cells through different mechanisms.

Commonly tested with

Venetoclax has been tested in clinical trials with:

• Obinutuzumab and rituximab (for CLL/SLL)
• Azacitidine, decitabine, and low-dose cytarabine (for AML)

Drug interaction studies have also been conducted with medications such as azithromycin, cytarabine, gastric acid reducing agents, ketoconazole, ritonavir, posaconazole, rifampin, warfarin, and digoxin to understand how these drugs may affect venetoclax levels or side effects.