Fedratinib (Inrebic) is a kinase inhibitor used for the treatment of adult patients with intermediate-2 or high-risk primary myelofibrosis (MF), or myelofibrosis secondary to polycythemia vera or essential thrombocythemia.

What Are the Side Effects of Fedratinib (Inrebic)?

Gastrointestinal Reactions

Diarrhea: The incidence rate reaches 66%.

Nausea: The incidence rate is 62%.

Vomiting: The incidence rate is 39%.

Others: Constipation (14%) and abdominal pain (10%).

Hematological Toxicity

Anemia: Occurs in 40% of patients, with 34% being Grade 3/4.

Thrombocytopenia: Occurs in 30% of patients, with 12% being Grade 3/4.

Neutropenia: Occurs in 23% of patients, with 5% experiencing severe reduction.

Systemic Reactions

Fatigue: Occurs in 19% of patients.

Muscle spasms: Reported by 12% of patients.

Weight loss: Occurs in 9% of patients.

Severe Side Effects of Fedratinib (Inrebic) That Require Vigilance

Encephalopathy (Including Wernicke Encephalopathy)

Severe encephalopathy occurs in 1.3% of patients during fedratinib treatment, with 0.16% being fatal.

Wernicke encephalopathy is a neurological emergency caused by thiamine (Vitamin B1) deficiency.

Symptoms include confusion, ataxia, ophthalmoplegia, etc.

Thiamine levels must be tested before treatment, and patients need to take daily thiamine supplements (100mg orally) during treatment.

If encephalopathy is suspected, discontinue the drug immediately and administer intravenous thiamine supplementation.

Severe Gastrointestinal Toxicity

The incidence rate of severe diarrhea (≥Grade 3) is 5%.

The incidence rate of severe vomiting (≥Grade 3) is 3.1%.

It can lead to dehydration, electrolyte imbalance, and malnutrition.

Antiemetic/antidiarrheal treatment should be initiated immediately when symptoms first appear.

Uveitis

Uveitis occurs in 4% of patients after fedratinib treatment.

Symptoms include eye pain, photophobia, vision loss, etc.

40% of cases are of Grade 3/4 severity.

27% of patients discontinue treatment due to this condition.

Precautions for Fedratinib (Inrebic) Administration

Treatment Monitoring Requirements

Hematology: Complete blood count (with particular attention to hemoglobin and platelets) should be checked weekly.

Liver function: ALT/AST should be checked before treatment and at regular intervals.

Amylase/lipase: Monitoring should be conducted at baseline and regular intervals.

Thiamine levels: Must be tested before treatment and rechecked regularly during treatment.

Electrocardiogram (ECG): Should be performed at baseline and rechecked before each treatment cycle.

Pregnancy and Lactation

It has embryo-fetal toxicity and is contraindicated during pregnancy.

Women of childbearing age need to use contraception during treatment and within 1 month after the last dose.

Male patients need to use contraception during treatment and within 3 months after the last dose.

It is contraindicated during lactation.