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/essential thrombocythemia.

Precautions for Fedratinib (Inrebic) Administration

Pre-Administration Assessment

Vitamin B1 Level Assessment: Thiamine (vitamin B1) levels must be measured before treatment. If deficiency exists, supplementation should be completed before initiating treatment.

Hematological Assessment: Baseline platelet count must be ≥ 50×10⁹/L, and hemoglobin and neutrophil levels should be evaluated.

Hepatic and Renal Function Assessment: Liver function indicators (ALT/AST/bilirubin) and renal function (creatinine clearance) need to be checked.

Cardiac Assessment: An electrocardiogram (ECG) is required to evaluate the QT interval.

Drug Interaction Assessment: Avoid concurrent use with strong CYP3A4 inhibitors/inducers.

Administration in Special Populations

Patients with Hepatic Impairment: No dose adjustment is needed for mild to moderate hepatic impairment; data on severe hepatic impairment is limited.

Patients with Renal Impairment: No dose adjustment is needed for mild to moderate renal impairment; for severe cases, reduce the dose to 200mg per day.

Elderly Patients: No dose adjustment is needed for patients ≥ 65 years old, but close monitoring is required.

Pregnant Women: Has embryotoxicity and should be avoided.

Lactating Women: Breastfeeding is prohibited during treatment and within 1 month after the last dose.

Management of Drug Interactions

Strong CYP3A4 Inhibitors: Such as ketoconazole, clarithromycin, etc. The dose of fedratinib needs to be reduced to 200mg per day.

Strong/Moderate CYP3A4 Inducers: Such as rifampicin, carbamazepine, etc. Concurrent use should be avoided.

Drugs That Are Substrates of CYP3A4/CYP2C19/CYP2D6: When used in combination, monitor for adverse reactions and consider dose adjustment.

Drugs That Are Substrates of OCT2 and MATE1/2-K: Such as metformin. When used in combination, monitor for adverse reactions.

Administration Monitoring of Fedratinib (Inrebic)

Encephalopathy and Vitamin B1 Monitoring

Monitoring Frequency: Thiamine levels must be measured before treatment and regularly during treatment.

Preventive Measures: All patients should take 100mg of oral thiamine daily as supplementation.

Symptom Monitoring: Pay attention to neurological symptoms such as confusion, ataxia, and ophthalmoplegia.

Management Measures: If encephalopathy is suspected, discontinue the drug immediately and initiate intravenous thiamine treatment.

Liver Function Monitoring

Elevated Transaminases: The incidence of ALT elevation is 43%, and AST elevation is 40%.

Monitoring Frequency: Regular monitoring before and during treatment.

Management Measures: Suspend drug administration if ALT/AST elevation reaches Grade 3 or higher.

After recovery, restart treatment with a daily dose reduced by 100mg.

If Grade 3 or higher elevation recurs, discontinue the drug permanently.

Amylase and Lipase Monitoring

Abnormal Elevation: The incidence of lipase elevation is 35%, with Grade 3 accounting for 10%.

Monitoring Frequency: Regular monitoring before and during treatment.