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Vandetanib Trade names Caprelsa Other names ZD6474 AHFS /Drugs.com Monograph MedlinePlus a611037 License data
US DailyMed : Vandetanib
US FDA : Vandetanib
Pregnancy
Routes of By mouth ATC code Legal status
AU S4 (Prescription only)
CA ℞-only
UK POM (Prescription only)
US WARNING [1] [2]
EU
Protein binding 90–96% Metabolism CYP3A4 , FMO1 , FMO3 Elimination half-life 19 days (mean)[2] Excretion 44% faeces, 25% urine
N
CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEBI ChEMBL PDB ligand CompTox Dashboard (EPA ) ECHA InfoCard 100.195.611 Formula C 22 H 24 Br F N 4 O 2 Molar mass −1 3D model (JSmol )
CN1CCC(CC1)COc2cc3c(cc2OC)c(ncn3)Nc4ccc(cc4F)Br
InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21 )29-2)22(26-13-25-19)27-18-4-3-15(23 )9-17(18 )24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27) Y
Key:UHTHHESEBZOYNR-UHFFFAOYSA-N Y
N Y (what is this?) (verify)
Vandetanib , sold under the brand name Caprelsa , is an anti-cancer medication that is used for the treatment of certain tumours of the thyroid gland . It acts as a kinase inhibitor of a number of cell receptors, mainly the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), and the RET -tyrosine kinase.[3] [4] AstraZeneca [2] Sanofi in 2015.[5] [6]
Medical use [ edit ]
Vandetanib is used to treat medullary thyroid cancer in adults who are ineligible for surgery.[2] [7] [8]
Contraindications [ edit ]
The V804M mutation in RET confers resistance to Vandetanib anti-RET activity.[8]
In people with moderate and severe hepatic impairment, no dosage for vandetanib has been recommended, as its safety and efficacy has not been established yet.[9] long QT syndrome .[2] [4]
Adverse effects [ edit ]
Very common (present in greater than 10% of people) adverse effects include colds, bronchitis, upper respiratory tract infections, urinary tract infections, decreased appetite, low calcium absorption , insomnia, depressed mood , Headache, tingling sensations , weird, painful sensations , dizziness, blurred vision, damage to the cornea , long QT syndrome , high blood pressure, stomach pain, diarrhea, nausea, vomiting, indigestion, sensitivity to sunlight , rash, acne, dry and itchy skin, nail disorders, protein in urine , kidney stones, weakness, fatigue, pain, and edema.[7]
Common (present in between 1% and 10% of people) adverse effects include pneumonia, sepsis, influenza, cystitis, sinusitis, laryngitis, folliculitis, boils , fungal infection, kidney infections , low thyroid hormone levels , low potassium , high calcium levels , hyperglycemia , dehydration, low sodium levels , anxiety, tremor, lethargy, loss of consciousness, balance disorders, changes in sense of taste , visual impairment, halo vision, perceived light flashes , glaucoma, pink eye , dry eye, keratopathy, hypertensive crisis , mini strokes , nose bleeds, coughing up blood , defecating blood, colitis, dry mouth, stomatitis , constipation, gastritis, gallstones , Chemotherapy-induced acral erythema , hair loss, painful urination, bloody urine, kidney failure , frequent urination, urgent need to urinate, and fever.[7]
Interactions [ edit ]
Vandetanib has been reported as a substrate for the OATP1B1 and OATP1B3 transporters. Interaction of vandetanib with OATP1B1 and OATP1B3 may alter its hepatic disposition and can lead to transporter mediated drug-drug interactions.[9] [10]
Other drugs that prolong the QT interval can possibly add to this side effect of vandetanib. As the drug is partly metabolised via the liver enzyme CYP3A4 , strong inducers of this enzyme can decrease its blood plasma concentrations. CYP3A4 inhibitors do not significantly increase vandetanib concentrations, presumably because it is also metabolised by flavin containing monooxygenase 1 (FMO1) and 3 [2] [4]
Pharmacology [ edit ]
Vandetanib is an inhibitor of vascular endothelial growth factor receptor -2, epidermal growth factor receptor , and RET tyrosine kinases . RET tyrosine kinases; it weakly inhibits VEGFR-3.[7] [11]
Metabolites of vandetanib (top left): N CYP3A4 ), vandetanib-N FMO1 and FMO3 ), both pharmacologically active, and a minor amount of a glucuronide .[12]
Vandetanib is well absorbed from the gut, reaches peak blood plasma concentrations 4 to 10 hours after application, and has a half-life of 19 days on average, per pharmacokinetic studies. It has to be taken for about three months to achieve a steady-state concentration. In the blood, it is almost completely (90–96%) bound to plasma proteins such as albumin . It is metabolised to N N active metabolites . Vandetanib is excreted via the faeces (44%) and the urine (25%) in form of the unchanged drug and the metabolites.[4] [13] [12]
History [ edit ]
Vandetanib was approved by the FDA in April 2011, for treatment of late-stage thyroid cancer.[14]
Vandetanib was first initially marketed without a trade name; it has been marketed under the trade name Caprelsa since August 2011.[15]
In 2015 Genzyme acquired the product from AstraZeneca.[16]
Research [ edit ]
AstraZeneca tested Vandetanib in clinical trials for non-small cell lung cancer and submitted an application for approval to the EMA but then withdrew the application in October 2009 after trials showed no benefit when the drug was administered alongside chemotherapy.[17] pancreatic carcinoma was negative in a prospective, randomised, double-blind, multicentre phase 2 trial.[18]
References [ edit ]
^ "Definition of vandetanib" . NCI Drug Dictionary . National Cancer Institute . 2011-02-02.
^ a b c d "Vandetanib Monograph" . Drugs.com. Retrieved 29 August 2012 .
^ "AZ sells rare cancer drug to Sanofi" . PMLive . 2015-07-27. Retrieved 2021-01-26 .
^ "Genzyme to Buy Caprelsa from AstraZeneca for Up to $300M" . GEN - Genetic Engineering and Biotechnology News . 2015-07-27. Retrieved 2021-01-26 .
^ a b c d "UK label" . www.medicines.org.uk . UK Electronic Medicines Compendium. 16 December 2016. Archived from the original on 28 February 2017. Retrieved 27 February 2017 .
^ a b Viola D, Valerio L, Molinaro E, Agate L, Bottici V, Biagini A, et al. (April 2016). "Treatment of advanced thyroid cancer with targeted therapies: ten years of experience" . Endocrine-Related Cancer . 23 4 ): R185–R205. doi :10.1530/ERC-15-0555 PMID 27207700 .
^ a b Khurana V, Minocha M, Pal D, Mitra AK (March 2014). "Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors" . Drug Metabolism and Drug Interactions . 29 3 ): 179–190. doi :10.1515/dmdi-2013-0062 . PMC 4407685 PMID 24643910 .
^ Khurana V, Minocha M, Pal D, Mitra AK (May 2014). "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors" . Drug Metabolism and Drug Interactions . 29 4 ): 249–259. doi :10.1515/dmdi-2014-0014 . PMC 4407688 PMID 24807167 .
^ Carlomagno F, Vitagliano D, Guida T, Ciardiello F, Tortora G, Vecchio G, et al. (December 2002). "ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases" . Cancer Research . 62 24 ): 7284–7290. PMID 12499271 .
^ a b "Clinical Pharmacology Review: Vandetanib" (PDF) . US Food and Drug Administration , Center for Drug Evaluation and Research. 20 August 2010. Retrieved 29 August 2012 .
^ Martin P, Oliver S, Kennedy SJ, Partridge E, Hutchison M, Clarke D, Giles P (January 2012). "Pharmacokinetics of vandetanib: three phase I studies in healthy subjects". Clinical Therapeutics . 34 1 ): 221–237. doi :10.1016/j.clinthera.2011.11.011 . PMID 22206795 .
^ "FDA approves new treatment for rare form of thyroid cancer" . Archived from the original on 10 April 2011. Retrieved 7 April 2011 .
^ Starkey J (August 2, 2011). "AstraZeneca (finally) lands name for cancer drug" . Delaware Inc .
^ Fourcade M (27 July 2015). "Sanofi to Buy Caprelsa Drug from AstraZeneca for $300 Million" . Bloomberg .
^ "Zactima" . European Medicines Agency . 17 September 2018.
^ Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, et al. (April 2017). "Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial" . The Lancet. Oncology . 18 4 ): 486–499. doi :10.1016/S1470-2045(17 )30084-0 . PMID 28259610 . S2CID 46676794 .
External links [ edit ]
"Vandetanib" . Drug Information Portal . U.S. National Library of Medicine.
t
e
CI monoclonal antibodies ("-mab")
Tyrosine kinase inhibitors ("-nib")
Receptor tyrosine kinase
RET inhibitors:Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib , Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib , Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR).
Non-receptor
Other
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e
Angiopoietin
CNTF
EGF (ErbB)
FGF
FGFR1
FGFR2
Agonists: Ersofermin
FGF (1 2 (bFGF) , 3 4 5 6 7 KGF ), 8 9 10 (KGF2) , 17 18 22
Palifermin
Repifermin
Selpercatinib
Sprifermin
Trafermin
FGFR3
FGFR4
Unsorted
HGF (c-Met)
IGF
LNGF (p75NTR )
PDGF
RET (GFL)
SCF (c-Kit)
TGFβ
Trk
TrkA
Negative allosteric modulators: VM-902A
TrkB
Agonists: 3,7-DHF
3,7,8,2'-THF
4'-DMA-7,8-DHF
7,3'-DHF
7,8-DHF
7,8,2'-THF
7,8,3'-THF
Amitriptyline
BDNF
BNN-20
Deoxygedunin
Deprenyl
Diosmetin
DMAQ-B1
HIOC
LM22A-4
N-Acetylserotonin
NT-3
NT-4
Norwogonin (5,7,8-THF)
R7
R13
TDP6
TrkC
VEGF
Others
Additional growth factors: Adrenomedullin
Colony-stimulating factors (see here instead)
Connective tissue growth factor (CTGF)
Ephrins (A1 , A2 , A3 , A4 , A5 , B1 , B2 , B3 )
Erythropoietin (see here instead)
Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
Glia maturation factor (GMF)
Hepatoma-derived growth factor (HDGF)
Interleukins /T-cell growth factors (see here instead)
Leukemia inhibitory factor (LIF)
Macrophage-stimulating protein (MSP; HLP, HGFLP)
Midkine (NEGF2)
Migration-stimulating factor (MSF; PRG4)
Oncomodulin
Pituitary adenylate cyclase-activating peptide (PACAP)
Pleiotrophin
Renalase
Thrombopoietin (see here instead)
Wnt signaling proteins
Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)
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Predecessors and
People
R e t r i e v e d f r o m " https://en.wikipedia.org/w/index.php?title=Vandetanib&oldid=1190943153 " C a t e g o r i e s : ● A n g i o g e n e s i s i n h i b i t o r s ● R e c e p t o r t y r o s i n e k i n a s e i n h i b i t o r s ● Q u i n a z o l i n e s ● A m i n e s ● B r o m o a r e n e s ● F l u o r o a r e n e s ● P h e n o l e t h e r s ● P i p e r i d i n e s ● D r u g s d e v e l o p e d b y A s t r a Z e n e c a ● S a n o f i H i d d e n c a t e g o r i e s : ● A r t i c l e s w i t h s h o r t d e s c r i p t i o n ● S h o r t d e s c r i p t i o n m a t c h e s W i k i d a t a ● D r u g s w i t h n o n - s t a n d a r d l e g a l s t a t u s ● A r t i c l e s w i t h c h a n g e d C A S N o i d e n t i f i e r ● E C H A I n f o C a r d I D f r o m W i k i d a t a ● D r u g h a s E M A l i n k ● D r u g b o x e s w h i c h c o n t a i n c h a n g e s t o v e r i f i e d f i e l d s
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