Information about Venetoclax
Venetoclax is an oral selective BCL-2 inhibitor and antineoplastic agent used in the therapy of refractory chronic lymphocytic leukemia (CLL).
Liver safety of Venetoclax
Venetoclax is associated with a low rate of transient serum enzyme elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury with jaundice. Venetoclax has potent immunosuppressive activity and may be capable of causing reactivation of hepatitis B.
Mechanism of action of Venetoclax
Venetoclax (ven et' oh klax) is a small molecule inhibitor of BCL-2, an intracellular protein that inhibits apoptosis. BCL2 is overexpressed in cancer cells, particularly in chronic lymphocyte leukemia (CLL). Overexpression of BCL2 increases cancer cell survival and increases resistance to chemotherapy. Venetoclax binds directly to BCL2 and blocks its antiapoptotic activity, leading to programmed cell death in the malignant B cells.
FDA approval information for Venetoclax
Venetoclax was found to have activity against refractory and relapsed CLL and was approved for use as an antineoplastic agent in the United States in 2016. Current indications are limited to therapy of previously treated patients with CLL and an accompanying 17p chromosomal deletion (which is associated with a poor prognosis and resistance to standard chemotherapy).
Dosage and administration for Venetoclax
Venetoclax is available as tablets of 10, 50 and 100 mg under the brand name Venclexta. The typical initial adult dose for CLL 20 mg once daily for one week with gradual dose escalation (“ramp-up”) to as much as 400 mg daily.
Side effects of Venetoclax
Side effects are common and include bone marrow suppression, neutropenia, infections, fever, diarrhea, nausea and vomiting, anorexia, abdominal discomfort and fatigue. Severe side effects include pneumonia, neutropenic fever and sepsis, autoimmune hemolytic anemia, embryo-fetal toxicity and tumor lysis syndrome (for which prophylactic measures are recommended during the ramp-up period).