Description

Simple

A chemotherapy drug used to treat certain types of kidney and liver cancer.

Clinical

A tyrosine kinase inhibitor used to treat renal cell carcinoma and hepatocellular carcinoma.

Overview

Cabozantinib was approved in 2012 and is a non-specific tyrosine kinase inhibitor. It is marketed as Cometriq, which is indicated for the treatment of metastatic medullary thyroid cancer. It's label includes a black box warning of gastrointestinal perforations, fistulas, and hemorrhage. The FDA approved cabozantinib as Cabometyx for patients with advanced renal cell carcinoma in April 2016.

Pharmacology

Indication

For the treatment of metastatic medullary thyroid cancer and for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

Pharmacodynamic

Cabozantinib suppresses metastasis, angiogenesis, and oncognesis by inhibiting receptor tyrosine kinases.

Mechanism of action

Cabozantinib inhibits specific receptor tyrosine kinases such as VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, RET, MET, and TIE-2.

Absorption

After oral administration, peak plasma concentration was achieved in 2-5 hours.

Protein binding

Cabozantinib has extensive plasma protein binding (≥ 99.7%).

Volume of distribution

The volume of distribution is 349L.

Clearance

At steady state, the clearance is 4.4 L/hr.

Half life

Cabozantinib has a long half-life of 55 hours.

Route of elimination

Cabozantinib is eliminated mostly by the feces (54%) and also by the urine (27%).

Toxicity

Cabozantinib has a black box warning of serious gastrointestinal fistulas and perforations, and potentially fatal hemoptysis and gastrointestinal hemorrhage.

Adverse Effects

Contraindications

  • Hypersensitivity:
    • false
  • Regions: US

Food Interactions

  • Avoid grapefruit products. Combination may increase levels of cabozantinib.

Interactions

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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 Cabozantinib can be decreased when combined with (R)-warfarin.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Cabozantinib.
3,5-diiodothyropropionic acid
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Cabozantinib.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Cabozantinib.
Abaloparatide
The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Cabozantinib.
Abatacept
The metabolism of Cabozantinib can be increased when combined with Abatacept.
Abiraterone
The metabolism of Cabozantinib can be decreased when combined with Abiraterone.
Acenocoumarol
The metabolism of Acenocoumarol can be decreased when combined with Cabozantinib.
Acetaminophen
The serum concentration of Acetaminophen can be increased when it is combined with Cabozantinib.
Acetohexamide
The metabolism of Cabozantinib can be decreased when combined with Acetohexamide.
Acetyl sulfisoxazole
The metabolism of Cabozantinib can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acid
The metabolism of Cabozantinib can be decreased when combined with Acetylsalicylic acid.
Adalimumab
The metabolism of Cabozantinib can be increased when combined with Adalimumab.
Afelimomab
The metabolism of Cabozantinib can be increased when combined with Afelimomab.
Agomelatine
The metabolism of Cabozantinib can be decreased when combined with Agomelatine.
Almotriptan
The metabolism of Almotriptan can be decreased when combined with Cabozantinib.
Alosetron
The metabolism of Cabozantinib can be decreased when combined with Alosetron.
Alpelisib
The serum concentration of Cabozantinib can be decreased when it is combined with Alpelisib.
Alprazolam
The metabolism of Cabozantinib can be decreased when combined with Alprazolam.
Aminophenazone
The metabolism of Cabozantinib can be decreased when combined with Aminophenazone.
5 References
  1. 1 . Durante C, Russo D, Verrienti A, Filetti S: XL184 (cabozantinib) for medullary thyroid carcinoma. Expert Opin Investig Drugs. 2011 Mar;20(3):407-413. doi: 10.1517/13543784.2011.559163.PubMed: 21314233
  2. 2 . Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25.PubMed: 26406150
  3. 3 . Krajewska J, Olczyk T, Jarzab B: Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer. Expert Rev Clin Pharmacol. 2016;9(1):69-79. doi: 10.1586/17512433.2016.1102052. Epub 2015 Nov 4.PubMed: 26536165
  4. 4 . Grullich C: Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. Recent Results Cancer Res. 2014;201:207-14. doi: 10.1007/978-3-642-54490-3_12.PubMed: 24756794
  5. 5 . Escudier B, Lougheed JC, Albiges L: Cabozantinib for the treatment of renal cell carcinoma. Expert Opin Pharmacother. 2016 Dec;17(18):2499-2504. doi: 10.1080/14656566.2016.1258059. Epub 2016 Nov 22.PubMed: 27835047