Formulation and Specifications: Tablets: 40 mg
Indications: This product is for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) carrying FMS-like tyrosine kinase 3 (FLT3) mutations as detected using a well-validated assay.
Key points for rational drug use:
1. Patients with relapsed or refractory AML must be identified as having a FLT3 mutation [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] in their peripheral blood or bone marrow prior to the use of giretinib fumarate tablets.
2. Baseline evaluation should be done prior to treatment and hematologic, cytogenetic and molecular biological responses should be monitored regularly during treatment in accordance with relevant disease guidelines.
3. The recommended starting dose of giretinib fumarate tablets is 120 mg once daily, every 28 days as a treatment cycle. Administered orally, whole tablets are to be taken with water, not broken or crushed, at approximately the same time each day. If a dose is missed or not taken at the scheduled time, it may be taken as soon as possible during the day, but should be made up 12 hours before the next scheduled dose and continued the next day at the normal scheduled time. The dose should be adjusted according to the efficacy and adverse effects during treatment.
4. Treatment with this product should be continued until the patient no longer has clinical benefit or develops intolerable toxicity. Because clinical remission may be delayed, consideration should be given to continuing treatment at the prescribed dose for up to 6 treatment cycles to ensure adequate time to achieve clinical remission.
5. If one of the following is not achieved after 4 weeks of treatment, the dose should be increased to 200 mg once daily if tolerated by the patient or clinically assured: (1) Complete remission (CR). (2) Complete remission (CRp) is achieved by all criteria except incomplete platelet recovery (platelets <100×109/L). (3) Complete remission (CRi) was achieved by all criteria except for remaining neutropenia (neutrophils <1×109/L) with or without complete platelet recovery.
6. Blood counts and blood biochemical assessments (including creatine phosphokinase) should be performed prior to the start of treatment, weekly in the 1st treatment cycle, week 2 in the 2nd treatment cycle, and each subsequent treatment cycle.
Patients with prolonged QTc intervals (>500 ms) should have their treatment interrupted and the dose of this product reduced.
8. Common adverse events (≥10%) were elevated ALT, elevated AST, anemia, thrombocytopenia, neutropenic fever, decreased platelet count, diarrhea, nausea, elevated blood alkaline phosphatase, fatigue, decreased white blood cell count, and elevated blood creatine phosphokinase.
9. This product is mainly metabolized by CYP3A4 enzyme and should be avoided in combination with potent CYP3A/P-glycoprotein inducers. When combined with potent CYP3A and/or P-glycoprotein inhibitors, the exposure of this product increases approximately 1.5-fold.
10. This product may reduce the efficacy of drugs targeting 5HT2B receptors or σ nonspecific receptors (e.g., escitalopram, fluoxetine, sertraline). The combination of these drugs with this product should be avoided unless it is confirmed that the benefit to the patient outweighs the risk.
11. No dose adjustment is required in patients with mild to moderate hepatic impairment. The use of this product in patients with severe hepatic impairment is not recommended because safety and efficacy have not been evaluated in this population.
12. Based on population pharmacokinetic modeling, no dose adjustment is required in patients with mild to moderate renal impairment. There is no clinical experience in patients with severe renal impairment.