Gilteritinib is an FLT3 tyrosine kinase inhibitor primarily used to treat relapsed/refractory acute myeloid leukemia (AML) with FLT3 mutation positivity. Its drug interactions mainly involve the CYP3A metabolic enzyme system, and there is a clinically significant risk of interaction with multiple drugs.

Pharmacological effects of Girotinib

1. Targeted inhibition: selectively inhibits FLT3-ITD and FLT3-TKD mutations, blocks downstream STAT5, ERK, and AKT signaling pathways, and induces apoptosis in leukemia cells.

2. Metabolic characteristics: Mainly metabolized through CYP3A4, with secondary pathways including UGT1A1 mediated glucuronidation.

Main drug interactions

1. CYP3A inhibitors: Combination with potent CYP3A inhibitors (such as itraconazole) can increase the exposure of gefitinib by more than 2 times. It is recommended to halve the dose or switch to alternative drugs.

2. CYP3A inducer: Combination with potent inducers such as rifampicin can reduce the AUC of gefitinib by 70%. Combination use should be avoided or consideration should be given to increasing the dose of gefitinib.

3. P-gp substrates: Girotinib may inhibit P-gp transporters, and its combination with P-gp substrates such as digoxin requires monitoring of the latter's blood drug concentration.

Special Interaction Precautions

1. Anticoagulants: may enhance the efficacy of anticoagulants such as warfarin, increase the risk of bleeding, and require close monitoring of INR values.

2. Hormonal contraceptives: may reduce estrogen exposure, non hormonal contraceptive measures are recommended.

3. Cardiotoxic drugs: Combined use with QT interval prolonging drugs may increase the risk of arrhythmia and require enhanced electrocardiogram monitoring.

Food interactions

1. Grapefruit products: containing potent CYP3A inhibitors, should be avoided from consumption.

2. High fat diet: can increase the AUC of Girotinib by 40%. It is recommended to have a fixed medication time and dietary pattern.