Fedratinib (Inrebic) is a kinase inhibitor. It is indicated for the treatment of adult patients with intermediate-2 or high-risk primary myelofibrosis, or myelofibrosis secondary to polycythemia vera or essential thrombocythemia.
How to Use Fedratinib (Inrebic)
Administration Regimen
Standard Dosage: The recommended starting dose is 400mg, administered orally once daily. It can be taken with or without food. This dosage is applicable to patients with a baseline platelet count ≥ 50×10⁹/L.
Special Administration Method: For patients with swallowing difficulties or those requiring nasogastric tube administration, the contents of the capsule can be dispersed in approximately 180mL of Ensure® Plus nutritional supplement, and the prepared mixture must be taken within 2 hours. If administered via a nasogastric tube (French size 14 or 16), the tube must be flushed with 60mL of water after administration.
Combination Medication: All patients must take 100mg of vitamin B1 (thiamine) orally daily as a preventive measure during fedratinib treatment.
Administration Instructions
Management of Missed Dose: If a dose is missed, skip that dose and take the next dose as scheduled on the following day. Do not take a double dose to make up for the missed one.
Monitoring Requirements
Serum thiamine levels must be measured before treatment. Patients with thiamine deficiency must receive supplementation before starting treatment.
During treatment, regularly monitor the complete blood count, liver function, amylase, and lipase levels.
Conduct regular electrocardiogram (ECG) examinations at baseline and during treatment to ensure QTcF < 450ms.
Dosage Adjustment of Fedratinib (Inrebic)
Hematologic Toxicity
Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with active bleeding: Discontinue treatment until recovery to ≤ Grade 2 or baseline. After recovery, reduce the daily dose by 100mg.
Grade 4 neutropenia: Discontinue treatment until recovery to ≤ Grade 2 or baseline. After recovery, reduce the daily dose by 100mg.
Gastrointestinal Toxicity
Grade 3 or higher diarrhea, nausea, or vomiting that does not respond to symptomatic treatment within 48 hours: Discontinue treatment until recovery to ≤ Grade 1. After recovery, reduce the daily dose by 100mg.
Liver Function Abnormalities
ALT/AST > 5×ULN: Discontinue treatment until recovery to ≤ Grade 1. After recovery, reduce the daily dose by 100mg. If the abnormality recurs, discontinue the drug permanently.
Drug Interactions
Strong CYP3A4 inhibitors (e.g., ketoconazole): Reduce the dose to 200mg per day.
After discontinuing strong CYP3A4 inhibitors: Adjust the dose to 300mg per day for the first two weeks, then resume the 400mg per day dose.
Strong/moderate CYP3A4 inducers: Avoid concurrent use.
Fedratinib (Inrebic) Use in Special Populations
Pregnancy and Lactation
Pregnancy: Animal studies have shown that fedratinib may cause abnormal fetal development. Women of childbearing age should take effective contraceptive measures during treatment and within 1 month after the last dose.
Lactation: Breastfeeding is prohibited during treatment and for at least 1 month after the last dose.
Elderly Patients
In clinical studies, 47.3% of patients were over 65 years old, and 12.3% were over 75 years old.
Elderly patients are more prone to adverse reactions and treatment interruptions; enhanced monitoring is required, but no special dose adjustment is needed.
Patients with Hepatic or Renal Impairment
Hepatic Impairment: No dose adjustment is needed for mild to moderate hepatic impairment. Use should be avoided in patients with severe hepatic impairment due to insufficient data.
Renal Impairment: For patients with severe renal impairment (CLcr 15-29mL/min), the dose should be halved. No dose adjustment is needed for mild to moderate renal impairment, but enhanced monitoring is required.
