Fedratinib: A Review of Its Pharmacology and Clinical Use

Abstract

Fedratinib (INREBIC®) is a JAK2-selective inhibitor that has been developed as an oral treatment for myelofibrosis. It was approved for the first time in the United States in August 2019 to treat adult patients with intermediate-2 or high-risk primary or secondary (post-polycythaemia vera or post-essential thrombocythemia) myelofibrosis. Fedratinib is an anilinopyrimidine derivative and is metabolized by CYP3A4, CYP2C19 and flavin-containing monooxygenase-3. Fedratinib is mainly excreted in faeces, and the effective half-life is 41 hours. The recommended dosage is 400 mg once daily (with or without food. The dosage should be reduced to 200 mg once daily in patients receiving CYP3A4 inhibitors and in patients with severe renal impairment. Fedratinib's recent approval adds to the few therapeutic option choices available to individuals with MF. The most common adverse events were mild gastrointestinal toxicities. Fedratinib comes with a boxed warning about the risk of serious and potentially deadly encephalopathies, such as Wernicke's.