Description

Simple

Clinical

Overview

Fedratinib, also known as SAR302503 and TG101348, is a tyrosine kinase inhibitor used to treat intermediate-2 and high risk primary and secondary myelofibrosis.[2,7] It is an anilinopyrimidine derivative.[6]

Fedratinib was granted FDA approval on August 16, 2019.[7]

Pharmacology

Indication

Fedratinib is indicated to treat adults with primary or secondary myelofibrosis that is either intermediate-2 or high risk.[7]

Pharmacodynamic

Fedratinib is a kinase inhibitor that inhibits cell division and induces apoptosis.[7] Patients taking fedratinib may experience anemia, thrombocytopenia, gastrointestinal toxicity, hepa... Read more

Mechanism of action

Fedratinib is an inhibitor of Janus Activated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3.[ Read more

Absorption

A 400mg oral dose results in a Cmax of 1804ng/mL and an AUC of 26,870ng/*hr/mL.[7] Fedratinib has a Tmax of 1.75-3 hours.[ Read more

Protein binding

Fedratinib is ≥92% protein bound in plasma.[7]

Volume of distribution

The apparent volume of distribution is 1770L.[7]

Clearance

The clearance of fedratinib is 13L/h.[7]

Half life

The half life of fedratinib is 41 hours with a terminal half life of 114 hours.[7]

Route of elimination

An oral dose of fedratinib is 77% eliminated in the feces with 23% as unchanged drug.[7] 5% is eliminated in the urine, with 3% as unchanged drug.[ Read more

Toxicity

Data regarding fedratinib in overdose is not readily available.[7] Patients given 680mg/day experienced a greater incidence and severity of adverse effects including anemia, thrombocytop... Read more

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

  • Take with or without food.

Interactions

Type in a drug name to check for interaction with Fedratinib
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of Fedratinib can be decreased when combined with (R)-warfarin.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Fedratinib.
3,5-diiodothyropropionic acid
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Fedratinib.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Fedratinib.
Abaloparatide
The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Fedratinib.
Abatacept
The metabolism of Fedratinib can be increased when combined with Abatacept.
Abemaciclib
The excretion of Abemaciclib can be decreased when combined with Fedratinib.
Abiraterone
The metabolism of Fedratinib can be decreased when combined with Abiraterone.
Acenocoumarol
The metabolism of Fedratinib can be decreased when combined with Acenocoumarol.
Acetaminophen
The serum concentration of Acetaminophen can be increased when it is combined with Fedratinib.
Acetyldigoxin
Fedratinib may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acyclovir
The excretion of Acyclovir can be decreased when combined with Fedratinib.
Adalimumab
The metabolism of Fedratinib can be increased when combined with Adalimumab.
Afatinib
The serum concentration of Afatinib can be increased when it is combined with Fedratinib.
Afelimomab
The metabolism of Fedratinib can be increased when combined with Afelimomab.
Allopurinol
Fedratinib may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Alpelisib
The serum concentration of Alpelisib can be increased when it is combined with Fedratinib.
Alvocidib
Fedratinib may decrease the excretion rate of Alvocidib which could result in a higher serum level.
Ambrisentan
The serum concentration of Ambrisentan can be increased when it is combined with Fedratinib.
Aminophenazone
The metabolism of Fedratinib can be decreased when combined with Aminophenazone.
7 References
  1. 1 . Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, Masszi T, Mishchenko E, Jourdan E, Vannucchi AM, Drummond MW, Jurgutis M, Kuliczkowski K, Gheorghita E, Passamonti F, Neumann F, Patki A, Gao G, Tefferi A: Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2015 Aug;1(5):643-51. doi: 10.1001/jamaoncol.2015.1590.PubMed: 26181658
  2. 2 . Jamieson C, Hasserjian R, Gotlib J, Cortes J, Stone R, Talpaz M, Thiele J, Rodig S, Pozdnyakova O: Effect of treatment with a JAK2-selective inhibitor, fedratinib, on bone marrow fibrosis in patients with myelofibrosis. J Transl Med. 2015 Sep 10;13:294. doi: 10.1186/s12967-015-0644-4.PubMed: 26357842
  3. 3 . Zhang M, Xu C, Ma L, Shamiyeh E, Yin J, von Moltke LL, Smith WB: Effect of food on the bioavailability and tolerability of the JAK2-selective inhibitor fedratinib (SAR302503): Results from two phase I studies in healthy volunteers. Clin Pharmacol Drug Dev. 2015 Jul;4(4):315-21. doi: 10.1002/cpdd.161. Epub 2014 Oct 27.PubMed: 27136912
  4. 4 . Zhang M, Xu CR, Shamiyeh E, Liu F, Yin JY, von Moltke LL, Smith WB: A randomized, placebo-controlled study of the pharmacokinetics, pharmacodynamics, and tolerability of the oral JAK2 inhibitor fedratinib (SAR302503) in healthy volunteers. J Clin Pharmacol. 2014 Apr;54(4):415-21. doi: 10.1002/jcph.218. Epub 2013 Nov 16.PubMed: 24165976
  5. 5 . Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM, Silverman MH, Gilliland DG, Shorr J, Tefferi A: Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol. 2011 Mar 1;29(7):789-96. doi: 10.1200/JCO.2010.32.8021. Epub 2011 Jan 10.PubMed: 21220608
  6. 6 . Roskoski R Jr: Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. Pharmacol Res. 2016 Sep;111:784-803. doi: 10.1016/j.phrs.2016.07.038. Epub 2016 Jul 26.PubMed: 27473820
  7. 7 . FDA Approved Drug Products: Fedratinib Oral Capsules Link