Description

Simple

Information currently not available.

Clinical

Information currently not available.

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

Effect Regions Age Groups Incidences Evidence Type
Anemia US
  • Kind: experimental
    • Percent: 74
  • Kind: placebo
    • Percent: 32
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 66
  • Kind: placebo
    • Percent: 16
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 62
  • Kind: placebo
    • Percent: 15
  • Clinical Trial
    Creatinine increased US
  • Kind: experimental
    • Percent: 59
  • Kind: placebo
    • Percent: 19
  • Clinical Trial
    Thrombocytopenia US
  • Kind: experimental
    • Percent: 47
  • Kind: placebo
    • Percent: 26
  • Clinical Trial
    ALT increased US
  • Kind: experimental
    • Percent: 43
  • Kind: placebo
    • Percent: 14
  • Clinical Trial
    AST increased US
  • Kind: experimental
    • Percent: 40
  • Kind: placebo
    • Percent: 16
  • Clinical Trial
    Anemia US
  • Kind: experimental
    • Percent: 40
  • Kind: placebo
    • Percent: 14
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 39
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Lipase increased US
  • Kind: experimental
    • Percent: 35
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Grade 3, grade 4, high-grade Anemia US
  • Kind: experimental
    • Percent: 34
  • Kind: placebo
    • Percent: 10
  • Clinical Trial
    Grade 3, grade 4, high-grade Anemia US
  • Kind: experimental
    • Percent: 30
  • Kind: placebo
    • Percent: 7
  • Clinical Trial
    Hyponatremia US
  • Kind: experimental
    • Percent: 26
  • Kind: placebo
    • Percent: 11
  • Clinical Trial
    Amylase increased US
  • Kind: experimental
    • Percent: 24
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Neutropenia US
  • Kind: experimental
    • Percent: 23
  • Kind: placebo
    • Percent: 13
  • Clinical Trial
    Fatigue or asthenia US
  • Kind: experimental
    • Percent: 19
  • Kind: placebo
    • Percent: 16
  • Clinical Trial
    Grade 3, grade 4, high-grade Thrombocytopenia US
  • Kind: experimental
    • Percent: 12
  • Kind: placebo
    • Percent: 10
  • Clinical Trial
    Muscle Spasms US
  • Kind: experimental
    • Percent: 12
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Grade 3, grade 4, high-grade lipase increased US
  • Kind: experimental
    • Percent: 10
  • Kind: placebo
    • Percent: 2
  • Clinical Trial
    Blood creatinine increased US
  • Kind: experimental
    • Percent: 10
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Pain in extremity US
  • Kind: experimental
    • Percent: 10
  • Kind: placebo
    • Percent: 4.2
  • Clinical Trial
    Weight increased US
  • Kind: experimental
    • Percent: 9
  • Kind: placebo
    • Percent: 4.2
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 9
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Alanine aminotransferase increased US
  • Kind: experimental
    • Percent: 9
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Bone pain US
  • Kind: experimental
    • Percent: 8
  • Kind: placebo
    • Percent: 2.1
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 8
  • Kind: placebo
    • Percent: 3.2
  • Clinical Trial
    Urinary Tract Infection US
  • Kind: experimental
    • Percent: 6
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Dysuria US
  • Kind: experimental
    • Percent: 6
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Neutropenia US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 3.3
  • Clinical Trial
    Grade 3, grade 4, high-grade Hyponatremia US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 4.3
  • Clinical Trial
    Aspartate aminotransferase increased US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Grade 3, grade 4, high-grade Diarrhea US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade fatigue or asthenia US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Grade 3, grade 4, high-grade creatinine increased US
  • Kind: experimental
    • Percent: 3.1
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Grade 3, grade 4, high-grade Vomiting US
  • Kind: experimental
    • Percent: 3.1
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade amylase increased US
  • Kind: experimental
    • Percent: 2.1
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade AST increased US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 1.1
  • Clinical Trial
    Grade 3, grade 4, high-grade ALT increased US
  • Kind: experimental
    • Percent: 1
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade blood creatinine increased US
  • Kind: experimental
    • Percent: 1
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Urinary Tract Infection US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade aspartate aminotransferase increased US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Muscle Spasms US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Dysuria US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Nausea US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Weight increased US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Pain in extremity US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Dizziness US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Headache US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade alanine aminotransferase increased US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Grade 3, grade 4, high-grade Bone pain US
  • Kind: experimental
    • Percent: 0
  • Kind: placebo
    • Percent: 0
  • Clinical Trial

    Contraindications

    Information currently not available.

    Food Interactions

    Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of fedratinib. Dose reduction may be necessary.

    Avoid St. John's Wort. This herb induces the CYP3A metabolism of fedratinib and may reduce its serum concentration.

    Take with or without food. Food may help reduce adverse effects of fedratinib such as nausea and vomiting.