- March 15, 2022
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Brand Name :
Inrebic
Synonyms :
fedratinib
Class :
Anti-cancer and Kinase Inhibitors
Dosage forms & Strengths
Capsule
100mg
fedratinib treats adults with a high risk of thrombocythemia or polycythemia (myelofibrosis). The oral dose for the adult patient for the same is 400 mg four times daily.
If the baseline platelet count is more than 50 x 109/L: 400mg orally each day
Dose Adjustments
If unable to tolerate the dose of 200mg per day, discontinue the treatment
Co-administration with strong CYP3A4 inhibitors
Reduce the dose of fedratinib to 200 mg each day
If strong CYP3A4 inhibitors are discontinued, increase the dose of fedratinib to 300 mg daily
Discontinue the usage of CYP3A4 inhibitors for initial 2 weeks. Continue the dose later to 400 mg each day
In case of hematologic adverse reactions, restart the dose with 100 mg per day
In case of high-grade nausea, diarrhea, and vomiting, interrupt the dose until it is resolved to lower grade baseline. Restart from 100 mg per day below the last given dose
In case of high-grade hepatoxicity, discontinue the treatment
Safety and efficacy of fedratinib are not found for pediatric dosing.
Refer to the adult dosing
abametapir increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
amobarbital decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
apalutamide decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
bosentan decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
butalbital decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
carbamazepine decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
darunavir increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
efavirenz decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
encorafenib decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
enzalutamide decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
fosphenytoin decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
idelalisib increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
lopinavir increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of mobocertinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
pacritinib increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
phenobarbital decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
rabeprazole increases the effect of fedratinib and vice versa
rifampin decreases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
saquinavir increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
tipranavir increases the effect of fedratinib by altering the intestinal/hepatic CYP3A4 enzyme metabolism
tucatinib increases the effect of fedratinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
voriconazole increases the effect of fedratinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
alfentanil increases the effect of fedratinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib: they may diminish the serum concentration of CYP3A4 Inducers
fedratinib: they may diminish the serum concentration of CYP3A4 Inducers
fedratinib: they may diminish the serum concentration of CYP3A4 Inducers
fedratinib: they may diminish the serum concentration of CYP3A4 Inducers
fedratinib: they may diminish the serum concentration of CYP3A4 Inducers
It may diminish the levels when combined with efavirenz by CYP3A4 metabolism
nafcillin will decrease the effect of action of fedratinib by affecting enzyme CYP3A4 metabolism.
the level or effect of fedratinib is increased by lenvatinib
CYP3A strong enhancers of the small intestine may reduce the bioavailability of fedratinib
fedratinib increases the effect of abemaciclib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of amlodipine by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of avanafil by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
belzutifan decreases the effect of abemaciclib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of bortezomib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of buspirone by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of cariprazine by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of ceritinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of darifenacin by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of dasatinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of deutetrabenazine by altering the intestinal/ hepatic CYP2D6 enzyme metabolism
fedratinib increases the effect of dihydroergotamine by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of elagolix by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of erlotinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of estropipate by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of everolimus by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of fenofibrate by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of fentanyl by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of flecainide by altering the intestinal/ hepatic CYP2D6 enzyme metabolism
fedratinib increases the effect of fluphenazine by altering the intestinal/ hepatic CYP2D6 enzyme metabolism
fedratinib increases the effect of gefitinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of guanfacine by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of haloperidol by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of irinotecan by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of ivacaftor by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of lacosamide by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of lefamulin by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of linagliptin by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of macimorelin by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of maraviroc by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of mestranol by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of metoprolol by altering the intestinal/ hepatic CYP2D6 enzyme metabolism
fedratinib increases the effect of montelukast by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of nebivolol by altering the intestinal/ hepatic CYP2D6 enzyme metabolism
fedratinib increases the effect of nortriptyline by altering the intestinal/ hepatic CYP2D6 enzyme metabolism
fedratinib increases the effect of omeprazole by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of paclitaxel by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of paricalcitol by altering the intestinal/ hepatic CYP3A4 enzyme metabolism fedra
fedratinib increases the effect of ritonavir by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of sunitinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
tezacaftor increases the effect of mestranol by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of ulipristal by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of verapamil by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of zolpidem by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of mestranol by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
It may enhance the serum concentration when combined with CYP3A4 Inhibitors (Moderate)
It may enhance the serum concentration when combined with CYP3A4 Inhibitors (Moderate)
It may enhance the serum concentration when combined with CYP3A4 Inhibitors (Moderate)
It may enhance the serum concentration when combined with CYP3A4 Inhibitors (Moderate)
It may enhance the serum concentration when combined with CYP3A4 Inhibitors (Moderate)
when both drugs are combined, there may be a decreased rate of excretion of paclitaxel
has a synergistic effect over brentuximab vedotin, by showing altered intestinal/hepatic CYP3A4 enzyme metabolism.
when both drugs are combined, there may be an increased level or effect of romidepsin by affecting hepatic or intestinal enzyme cyp3a4 metabolism
fedratinib increases the effect of ixazomib by altering intestinal/hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect of gefitinib by altering the intestinal/ hepatic CYP3A4 enzyme metabolism
fedratinib increases the effect or level of midostaurin by altering the CYP3A4 enzyme metabolism
idelalisib increases the effect or level of fedratinib by altering the intestinal/hepatic CYP3A4 metabolism
it increases the effect or level of palbociclib by altering the intestinal or hepatic CYP3A4 enzyme metabolism
Actions and Spectrum:
Actions:
fedratinib is a selective and potent inhibitor of the Janus kinase 2 (JAK2) enzyme, which plays a crucial role in the signaling pathways of various cytokines and growth factors. By inhibiting JAK2, fedratinib can block the activation of downstream signaling pathways, which are implicated in the growth and proliferation of certain types of cancer cells.
Spectrum:
The spectrum of fedratinib refers to the range of conditions against which it is effective. fedratinib is a selective inhibitor of the JAK2 enzyme, which is involved in the signaling pathways of various cytokines and growth factors. Therefore, fedratinib has been studied primarily for treating hematological malignancies, including myelofibrosis, polycythemia vera, and essential thrombocythemia.
Frequency defined:
>10%
Diarrhea
Nausea
Anemia
Blood creatinine increased
Thrombocytopenia
ALT increased
AST increased
Vomiting
Lipase Increased
Hyponatremia
Amylase increased
Neutropenia
Fatigue or asthenia
Muscle spasms
1-10%
Pain in extremity
Headache
Weight increased
Dizziness
Bone pain
Urinary tract infection
Dysuria
Hypertension
Black-Box Warning:
Encephalopathy
Wernicke encephalopathy is a severe and potentially fatal condition that can occur in patients taking fedratinib. Thiamine deficiency is a known risk factor for Wernicke encephalopathy, and it is recommended that thiamine levels be assessed in all patients before starting treatment with fedratinib.
If thiamine deficiency is detected, it should be corrected before starting treatment with fedratinib. Patients should be monitored for symptoms of encephalopathy during treatment, and treatment should be immediately discontinued if encephalopathy is suspected.
If encephalopathy is diagnosed, parenteral thiamine should be initiated immediately, and patients should be closely monitored until symptoms resolve or improve and thiamine levels normalize. Early recognition and treatment of encephalopathy are critical to preventing severe complications and death.
Contraindications/Caution:
Contraindications:
Caution:
Pregnancy consideration: The drug is unsafe for pregnant women and the developing fetus.
Lactation: No data available regarding the excretion of fedratinib in breast milk. Hence, potential adverse effects and potential benefits should be compared and considered.
Pregnancy category:
Pharmacology:
fedratinib is a selective inhibitor of Janus kinase 2 (JAK2), which is a tyrosine kinase involved in signaling pathways for a number of cytokines and growth factors, including erythropoietin, thrombopoietin, and interleukins.
Pharmacodynamics:
By inhibiting JAK2, fedratinib prevents the downstream activation of STAT (signal transducer and activator of transcription) proteins, which play a key role in the signaling pathway for JAK2. This results in decreased proliferation and survival of malignant cells in diseases such as myelofibrosis and polycythemia vera.
Pharmacokinetics:
The pharmacokinetics of fedratinib is described as:
Absorption
fedratinib is rapidly absorbed after oral administration
Distribution
It reaches peak plasma concentration within 2 hours. Its bioavailability is approximately 30% and is increased with food.
Metabolism
fedratinib is extensively metabolized in the liver by CYP3A4
Elimination/Excretion
The drug is excreted in feces and urine.
Administration:
fedratinib is administered orally in the form of capsules and should be taken with food to increase its bioavailability. The recommended dose of fedratinib for the treatment of myelofibrosis is 400 mg orally once daily.
If a dose of fedratinib is missed, it should be taken as soon as possible unless it is within 12 hours of the next scheduled dose. In this case, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time. fedratinib capsules should not be opened, crushed, or chewed.
If a patient has difficulty swallowing the capsules, they can be opened, and the contents sprinkled on applesauce immediately before administration. The applesauce should be swallowed whole without chewing, followed by a glass of water to ensure that all of the medication is swallowed.
Patient information leaflet
Generic Name: fedratinib
Pronounced: feh-drah-tih-nib
Why do we use fedratinib?
fedratinib is a medication that is used to treat certain blood disorders, specifically myelofibrosis, which is a type of bone marrow disorder that causes abnormal blood cell production and scarring of the bone marrow. Myelofibrosis can cause a range of symptoms, including fa
