Axitinib

Synonyms :
SID103905539

Status : approved

Therapeutic Classification

OTHER ANTINEOPLASTIC AGENTS

ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS

Description

Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3. Axitinib is marketed under the name Inlyta®, and if one previous systemic therapy for kidney cell cancer has failed, axitinib is indicated.

Used

Used in kidney cell cancer and investigated for use/treatment in pancreatic and thyroid cancer.

Mechanism Of Action

Axitinib selectively blocks the tyrosine kinase receptors VEGFR-1 (vascular endothelial growth factor receptor), VEGFR-2, and VEGFR-3.

Dosage

Form Route Strength
Tablet oral 1 mg
Tablet oral 3 mg
Tablet oral 5 mg
Tablet oral 7 mg
Tablet, film coated oral 1 mg
Tablet, film coated oral 5 mg

Pharmacodynamics

Axitinib prevents the progression of cancer by inhibiting angiogenesis and blocking tumor growth.

Toxic Effect

Some of the more serious toxic effects seen in patients taking axitinib include, but are not limited to, hypertension, thrombotic events, hemorrhage, and GI perforation.

Metabolism

Axitinib undergoes mainly hepatic metabolism. CYP3A4 and CYP3A5 are the main hepatic enzymes while CYP1A2, CYP2C19, and UGT1A1 enzymes are secondary.

Absorption

After one 5 mg dose of axitinib, it takes about 2.5 to 4.1 hours to reach maximum plasma concentration.

Half Life

Axitinib has a half life of 2.5 to 6.1 hours.

Protein Binding

Plasma protein binding for axitinib is high at over 99% with most protein binding to albumin followed by α1-acid glycoprotein.

Elimination Route

Axitinib is mainly eliminated unchanged in the feces (41%) with 12% of the original dose as unchanged axitinib. There is also 23% eliminated in the urine, most of which are metabolites.

Clearance

The average clearance of axitinib is 38 L/h.

Volume of Distribution

The volume of distribution is 160 L.

Chemical Classification

Chemical Name

SID103905539

Brands

name Dosage form Country
Inlyta tablet Canada
Inlyta tablet Canada
Inlyta tablet, film coated US
Inlyta tablet Canada
Inlyta tablet Canada
Inlyta tablet, film coated US
Inlyta tablet, film coated US

Drug Drug Interactions

  •  Aprepitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Atazanavir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Bexarotene  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Boceprevir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Bosentan  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Carbamazepine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Ceritinib  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Clarithromycin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Cobicistat  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Conivaptan  : May increase the serum concentration of CYP3A4 Substrates.
  •  Dabrafenib  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Darunavir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Dasatinib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Deferasirox  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Dexamethasone  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Efavirenz  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Enzalutamide  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Eslicarbazepine acetate  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Etravirine  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Fosaprepitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Fosphenytoin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Idelalisib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Indinavir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Itraconazole  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Ivacaftor  : May increase the serum concentration of CYP3A4 Substrates.
  •  Ketoconazole  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Lopinavir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Luliconazole  : May increase the serum concentration of CYP3A4 Substrates.
  •  Mifepristone  : May increase the serum concentration of CYP3A4 Substrates.
  •  Mitotane  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Modafinil  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Nafcillin  : CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib.
  •  Nefazodone  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Nelfinavir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Netupitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Palbociclib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Phenobarbital  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Phenytoin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Posaconazole  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Primidone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Rifabutin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Rifampicin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Rifapentine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Ritonavir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Saquinavir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Siltuximab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Simeprevir  : May increase the serum concentration of CYP3A4 Substrates.
  •  Stiripentol  : May increase the serum concentration of CYP3A4 Substrates.
  •  Telaprevir  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Telithromycin  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
  •  Tocilizumab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Voriconazole  : CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.

Food Interactions

  • Avoid combination with strong CYP3A4 inhibitors such as grapefruit juice due to the likely increased levels of axitinib. If the combination cannot be avoided, reduce axitinib dose by 50%., Axitinib can be taken with or without food.

Calculated Property

kind Value Source

Affected organism

Humans and other mammals

Target within organism

  • Vascular endothelial growth factor receptor 1 : in Human
  • Vascular endothelial growth factor receptor 2 : in Human
  • Vascular endothelial growth factor receptor 3 : in Human