Fedratinib

Fedratinib Uses, Dosage, Side Effects, Food Interaction and all others data.

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

Fedratinib was granted FDA approval on August 16, 2019.

Fedratinib is a kinase inhibitor that inhibits cell division and induces apoptosis. Patients taking fedratinib may experience anemia, thrombocytopenia, gastrointestinal toxicity, hepatic toxicity, or elevated amylase and lipase. These effects should be managed by reducing the dose, temporarily stopping the medication, or providing transfusions on a case by case basis.

Trade Name Fedratinib
Availability Prescription only
Generic Fedratinib
Fedratinib Other Names Fedratinib
Related Drugs Jakafi, ruxolitinib, Vonjo, pacritinib, Inrebic
Weight 100mg
Type Oral capsule
Formula C27H36N6O3S
Weight Average: 524.678
Monoisotopic: 524.256959738
Protein binding

Fedratinib is ≥92% protein bound in plasma.

Groups Approved, Investigational
Therapeutic Class
Manufacturer
Available Country United States
Last Updated: September 19, 2023 at 7:00 am
Fedratinib
Fedratinib

Uses

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

Fedratinib is also used to associated treatment for these conditions: Primary Myelofibrosis, Secondary Myelofibrosis

How Fedratinib works

Fedratinib is an inhibitor of Janus Activated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3. JAK2 is highly active in myeloproliferative neoplasms like myelofibrosis. Fedratinib's inhibition of JAK2 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5, which prevents cell division and induces apoptosis.

Toxicity

Data regarding fedratinib in overdose is not readily available. Patients given 680mg/day experienced a greater incidence and severity of adverse effects including anemia, thrombocytopenia, gastrointestinal toxicity, hepatic toxicity, and elevated amylase and lipase. These effects were treated symptomatically as well as by reducing the dose or temporarily stopping fedratinib.

Food Interaction

  • 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.

[Moderate] MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability).

In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.

Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4.

Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

Orange juice is not expected to interact with these drugs.

Volume of Distribution

The apparent volume of distribution is 1770L.

Elimination Route

A 400mg oral dose results in a Cmax of 1804ng/mL and an AUC of 26,870ng/*hr/mL. Fedratinib has a Tmax of 1.75-3 hours. A high fat breakfast does not significantly affect the absorption of fedratinib.

Half Life

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

Clearance

The clearance of fedratinib is 13L/h.

Elimination Route

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

Innovators Monograph

You find simplified version here Fedratinib

*** Taking medicines without doctor's advice can cause long-term problems.
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