Venetoclax is used as a second line treatment for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have shown disease progression after, or intolerance to a prior line of treatment.
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 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.
In October 2016 a European Medicines Agency committee recommended conditional marketing approval for venetoclax for CLL in the presence of 17p deletion or TP53 mutation; the drug had already been granted orphan status in 2012 for that use.