FEDRATINIB CAP,ORAL

Clinical Criteria Summary

Intermediate (INT)-2- or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera or post-essential thrombocythemia)
Splenomegaly by palpation (at least 5 cm below costal margin) or imaging
ECOG performance status of 0 to 2

Absolute neutrophil count less than 1.0 x 109/L
Platelet count less than 50 x 109/L
Thiamine level within the normal reference range used by local laboratory; if deficient, replete thiamine prior to initiating fedratinib
Ruxolitinib medically inadvisable due to absolute neutrophil count persisting below 0.75 x 109/L (note: to give fedratinib, neutropenia should be grade ≤ 2 and platelet count ≥ 50 x 109/L)
Fedratinib prescribed at the FDA-approved dose for myelofibrosis, modified as recommended for severe renal impairment (CrCl 15–29 mL/min), Grade 3 or 4 toxicities, and treatment-emergent transfusion dependence

History of recurrent Wernicke’s encephalopathy
Active, uncontrolled systemic or localized infection
Untreated latent or active tuberculosis infection
Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
Active hepatitis A
Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis
Antiviral prophylaxis for HBV: Agents with high genetic barrier to resistance such as entecavir or tenofovir should be used
Completed hepatitis B screening (at minimum, HBsAg, anti-HBc and anti-HBs)
Anti-HBs may help to identify patients who require initial or booster vaccination (anti-HBs titers >= 10 IU/L are generally considered protective) or HBsAg-negative patients without past vaccination who have occult HBV from past infection (anti-HBs positive and lost anti-HBc)
Untreated hepatitis C
Completed hepatitis C screening
Untreated HIV infection or at high risk for HIV infection

Severe liver impairment (Child-Pugh Class C)
Total bilirubin ≥ 3.0 x ULN
AST or ALT ≥ 2.5 x ULN
History of chronic liver disease, unless a hepatologist documents that fedratinib may be initiated safely
Serum amylase or lipase > 1.5 x ULN

Uncontrolled NYHA Class 3 or 4 heart failure, unless a cardiologist documents that fedratinib may be initiated safely

Strong or moderate CYP3A4 inDUCers (e.g., rifampin)
Dual CYP3A4 and CYP2C19 inhibitors (e.g., fluvoxamine)
Concomitant fluconazole required at doses greater than 200 mg daily
Fedratinib prescribed with modifications recommended for CYP3A4 inhibitor drug interactions
Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation

Breastfeeding
For women of childbearing age and men who partner with women of childbearing potential: Provided counseling on use of effective contraception to prevent pregnancy and on risks and benefits of treatment

Unable to comply with recommended laboratory monitoring
Patient able and willing to have hemoglobin monitored for transfusion requirement
Patient able and willing to have thiamine levels monitored
Care provided by a VA / VA Community Care hematologist or locally designated myelofibrosis expert
Goals of care and role of Palliative Care consult discussed and documented
Ruxolitinib is medically inadvisable, not tolerated despite dosage modifications, or not adequate
For patients on ruxolitinib: Ruxolitinib has been tapered and discontinued before initiation of fedratinib
Not adequate refers to NO spleen size reduction or myelofibrosis symptom improvement, or worsening of spleen size or myelofibrosis symptoms after 6 months of ruxolitinib therapy, or loss of initial response

Uncontrolled alcohol use disorder
Patient will receive antiemetics (e.g., ondansetron) to prevent or treat fedratinib-induced nausea or vomiting

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