Fedratinib (Specialist drug)

How it works

It is a selective JAK2 inhibitor that blocks signalling through the JAK-STAT pathway, which is dysregulated in myeloproliferative disease, reducing splenomegaly and constitutional symptoms.

Prescribing in practice

• Serious and potentially fatal encephalopathy, including Wernicke's encephalopathy, has been reported; thiamine levels must be assessed and corrected before and during treatment and the drug stopped if encephalopathy is suspected.
• Initiate only under specialist haematology supervision, with dose adjustment in renal impairment and avoidance in significant hepatic impairment.
• It causes myelosuppression and gastrointestinal toxicity, and interacts with strong CYP3A4 inhibitors and inducers.

Monitoring

Monitor thiamine levels, full blood count, and hepatic and renal function before and during treatment.

Counselling the patient

• Report confusion, memory problems, unsteadiness or vision changes immediately.
• Nausea, vomiting and diarrhoea are common and should be reported if severe so they can be managed.
• Do not stop or change the dose without specialist advice, and avoid grapefruit.

Evidence & guidelines

The JAKARTA trials established fedratinib's efficacy in reducing spleen volume and symptom burden in myelofibrosis, informing its licensed use.