Venetoclax

Venetoclax, sold under the trade name Venclexta and Venclyxto, is a medication used to treat chronic lymphocytic leukemia (CLL). Venetoclax, sold under the trade name Venclexta and Venclyxto, is a medication used to treat chronic lymphocytic leukemia (CLL). Venetoclax is used for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Indication does not depend on mutation status (e. g. 17p deletion, IGHV mutation, 12+). Venetoclax is also used as part of a combination therapy for acute myeloid leukemia (AML). For this purpose it is with azacitidine, decitabine, or low-dose cytarabine for newly-diagnosed adults over 75, or those with other health problems where intensive chemotherapy cannot be used. Common side effects of venetoclax include neutropenia (low white blood cell count), nausea, anemia, diarrhea, upper respiratory tract infection, fatigue, and thrombocytopenia (low platelet count). Major side effects include tumor lysis syndrome and severe neutropenia. Additionally, this drug may cause fertility problems in males. Venetoclax is a BH3-mimetic. Venetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells. Overexpression of Bcl-2 in some lymphoid malignancies has sometimes shown to be linked with increased resistance to chemotherapy. The maximum plasma concentration achieved after oral administration occurred 5-8 hours after dose. Steady state maximum concentration with low-fat meal conditions at the 400 mg once daily dose was found to be 2.1 ± 1.1 μg/mL. It is recommended that Venetoclax be administered with a meal. The apparent volume of distribution for venetoclax is approximately 256–321 L. It is highly bound to human plasma protein. Within a concentration range of 1-30 μM (0.87-26 μg/mL), the fraction unbound in plasma was less than 0.01. Venetoclax is metabolized by CYP3A4/5 as proven by in-vitro studies. Those using the drug should not consume grapefruit products because they contain CYP3A inhibitors. Additionally, while using venetoclax it is not recommended to use other drugs which contain CYP3A inhibitors (i.e.: erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil). Venetoclax is excreted from the body via the fecal route. In 2015, the United States Food and Drug Administration (FDA) granted the breakthrough therapy designation to venetoclax for people with CLL or SLL who have relapsed, become intolerant to, or refractory to previous treatment.