Feasibility and potential risks of combined use of venetoclax/venetoclax and posaconazole

In recent years, the U.S. Food and Drug Administration (FDA) has approved combination treatment regimens of hypomethylating drugs (HMAs) such as azacytidine or decitabine and venetoclax, especially for acute myeloid leukemia (AML) patients over the age of 75 and those who are not suitable for intensive chemotherapy. Venetoclax As a highly efficient and selective inhibitor of B-cell lymphoma 2 (BCL-2), it has shown stable efficacy whether as a single treatment or in combination with other drugs.

However, early in treatment, patients are at risk of fungal infection. In this setting, posaconazole is often used as first-line prophylaxis and is more effective than other azoles in preventing invasive fungal infections in neutropenic AML patients. While past studies have shown that venetoclax is well tolerated at single doses of 800 and 1200 mg in patients with relapsed or refractory AML, drug-drug interactions become particularly critical when it is combined with a strong CYP3A4 inhibitor such as posaconazole.

At present, the trends in serum levels associated with the combined use of venetoclax and posaconazole are not well understood. Since posaconazole can increase the plasma concentration of venetoclax, this may result in a number of unknown physiological effects and potential risks. Therefore, patients should carefully consider the combined use of these two drugs in the absence of clear clinical guidance and physician advice.

Overall, although venetoclax and posaconazole each have significant efficacy in their therapeutic areas, the safety and efficacy of their combined use still require further clinical research and evaluation.