What are the precautions for using midostaurin?

In clinical studies of Midostaurin (Midostaurin) in the treatment of acute myeloid leukemia (AML) and systemic mastocytosis, warnings and precautions such as embryo-fetal toxicity, pulmonary toxicity, severe neutropenia and thrombocytopenia have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Embryo-Fetotoxicity: Based on its mechanism of action and the results of animal reproduction studies, midostaurin may cause harm to the fetus when used in pregnant women. In animal studies, midostaurin has caused embryo-fetal toxicity, including late embryo-fetal death and reduced fetal birth weight, at doses lower than those recommended for humans, and resulted in delayed fetal growth.

Inform pregnant women of potential risks to the fetus. Verify pregnancy status in females of reproductive potential within 7 days before initiating treatment with midostaurin. Advise females of reproductive potential to use effective contraception during medication and for 4 months after the last dose; advise males of female partners of reproductive potential to use effective contraception during medication and for 4 months after the last dose.

2. Pulmonary toxicity: Cases of interstitial lung disease and pneumonia, some of which were fatal, have occurred in patients receiving midostaurin monotherapy or chemotherapy. Monitor patients for pulmonary symptoms. Midostaurin should be discontinued in patients who develop signs or symptoms of interstitial lung disease or pneumonia without an infectious etiology.

3. Risk of long-term severe neutropenia and thrombocytopenia in pediatric patients receiving combination chemotherapy: Two children who received unapproved midostaurin combination chemotherapy (including anthracyclines, fludarabine, and cytarabine)< span>A patient with AML developed prolonged grade 4 neutropenia and thrombocytopenia; both patients were concurrently taking an azole antifungal agent, a strong CYP3A4 inhibitor, which may increase midostaurin concentrations and thereby increase the risk of toxicity. The safety and effectiveness of midostaurin in pediatric patients have not been established.