|Trade names||Inlyta, Axinix|
|Drug class||Tyrosine kinase inhibitor|
|Main uses||Renal cell cancer (RCC)|
|Side effects||Diarrhea, high blood pressure, tiredness, nausea, weight loss, weakness, constipation|
|Typical dose||5 mg BID|
|Metabolism||Liver (mostly CYP3A4/CYP3A5-mediated but with some contributions from CYP1A2, CYP2C19, UGT1A1)|
|Elimination half-life||2.5-6.1 hours|
|Excretion||Feces (41%; 12% as unchanged drug), urine (23%)|
|Chemical and physical data|
|Molar mass||386.47 g·mol−1|
|3D model (JSmol)|
Axitinib, sold under the brand name Inlyta, is a medication used to treat renal cell cancer (RCC). It is used in advanced disease, either alone or with avelumab or pembrolizumab. It increased time to getting worse to 6.7 months from 4.7 months in those taking sorafenib. It is taken by mouth.
Common side effects include diarrhea, high blood pressure, tiredness, nausea, weight loss, weakness, and constipation. Other side effects may include blood clots, bleeding, heart failure, gastrointestinal perforation, low thyroid, poor wound healing, liver problems, and reversible posterior leukoencephalopathy syndrome (RPLS). Use in pregnancy may harm the baby. It is a tyrosine kinase inhibitor that blocks vascular endothelial growth factor (VEGF).
Axitinib was approved for medical use in the United States and Europe in 2012. In the United Kingdom 4 weeks of treatments costs the NHS about £3,500 as of 2021. In the United States this amount costs about 17,300 USD.
Renal cell cancer
It has received approval for use as a treatment for renal cell carcinoma from the US Food and Drug Administration (FDA) (27 January 2012), the European Medicines Agency (EMA) (13 September 2012), the UK Medicines and Healthcare products Regulatory Agency (MHRA) (3 September 2012) and the Australian Therapeutic Goods Administration (TGA) (26 July 2012).
Diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation are the most common side effects occurring in more than 20% of patients.
Mechanism of action
Its primary mechanism of action is thought to be vascular endothelial growth factor receptor 1-3, c-KIT and PDGFR inhibition, this, in turn, enables it to inhibit angiogenesis (the formation of new blood vessels by tumours).
|Bioavailability||Tmax||Cmax||AUC||Vd||Plasma protein binding||Metabolising enzymes||t1/2||Excretion routes|
|58%||2.5-4.1 hr||27.8 ng/mL||265 ng•h/mL||160 L||>99%||Mostly CYP3A4 and CYP3A5. Lesser contributions from CYP1A2, CYP2C19, UGT1A1||2.5-6.1 hr||Faeces (41%), urine (23%)|
Society and culture
In Bangladesh it is under the trade name Axinix.
A Phase II clinical trial showed good response in combination chemotherapy with gemcitabine for advanced pancreatic cancer. However, Pfizer reported on January 30, 2009 that Phase III clinical trials of the drug when used in combination with gemcitabine showed no evidence of improved survival rates over treatments using gemcitabine alone for advanced pancreatic cancer and halted the trial.
In 2010, a Phase III trial for previously treated metastatic renal cell carcinoma (mRCC) showed significantly extended progression-free survival when compared to sorafenib. In December 2011, the Oncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend that US FDA approve axitinib for the second-line treatment of patients with advanced renal cell carcinoma (RCC), based on the results of the Phase III trial comparing axitinib and sorafenib.
A study published in 2015 showed that axitinib effectively inhibits a mutated gene (BCR-ABL1[T315I]) that is common in chronic myeloid leukemias and adult acute lymphoblastic leukemias which have become resistant to other tyrosine kinase inhibitors like imatinib. This is one of the first examples of a new indication for an existing drug being discovered by screening known drugs using a patient's own cells.
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