Vandetanib

Source: Wikipedia, the free encyclopedia.
Vandetanib
Clinical data
Trade namesCaprelsa
Other namesZD6474
AHFS/Drugs.comMonograph
MedlinePlusa611037
License data
Pregnancy
category
  • AU: D
Routes of
administration		By mouth
ATC code
Legal status
Legal status
FMO3
Elimination half-life19 days (mean)[2]
Excretion44% faeces, 25% urine
Identifiers
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
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) checkY
  • Key:UHTHHESEBZOYNR-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Vandetanib, sold under the brand name Caprelsa, is an

vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), and the RET-tyrosine kinase.[3][4] The drug was developed by AstraZeneca[2] who later sold the rights to Sanofi in 2015.[5][6]

Medical use

Vandetanib is used to treat medullary thyroid cancer in adults who are ineligible for surgery.[2][7][8]

Contraindications

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] Vandetanib is contraindicated in people with congenital long QT syndrome.[2][4]

Adverse effects

Very common (present in greater than 10% of people) adverse effects include colds, bronchitis, upper respiratory tract infections, urinary tract infections, decreased appetite,

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,

gallstones, Chemotherapy-induced acral erythema, hair loss, painful urination, bloody urine, kidney failure, frequent urination, urgent need to urinate, and fever.[7]

Interactions

Vandetanib has been reported as a substrate for the

OATP1B3 transporters. Interaction of vandetanib with OATP1B1 and OATP1B3 may alter its hepatic disposition and can lead to transporter mediated drug-drug interactions.[9] Also, vandetanib is an inhibitor of OATP1B3 transporter but not for OATP1B1.[10]

Other drugs that

3.[2][4]

Pharmacology

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]

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-desmethylvandetanib via CYP3A4 and to vandetanib-N-oxide via FMO1 and 3. Both of these are 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

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

AstraZeneca tested Vandetanib in clinical trials for

pancreatic carcinoma was negative in a prospective, randomised, double-blind, multicentre phase 2 trial.[18]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ a b c d e f "Caprelsa- vandetanib tablet, film coated". DailyMed. 19 June 2020. Retrieved 8 December 2020.
  3. ^ "Definition of vandetanib". NCI Drug Dictionary. National Cancer Institute. 2011-02-02.
  4. ^ a b c d "Vandetanib Monograph". Drugs.com. Retrieved 29 August 2012.
  5. ^ "AZ sells rare cancer drug to Sanofi". PMLive. 2015-07-27. Retrieved 2021-01-26.
  6. ^ "Genzyme to Buy Caprelsa from AstraZeneca for Up to $300M". GEN - Genetic Engineering and Biotechnology News. 2015-07-27. Retrieved 2021-01-26.
  7. ^ 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.
  8. ^
    PMID 27207700
    .
  9. ^
    PMID 24643910
    .
  10. PMID 24807167
    .
  11. PMID 12499271
    .
  12. ^ 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.
  13. PMID 22206795
    .
  14. ^ "FDA approves new treatment for rare form of thyroid cancer". Archived from the original on 10 April 2011. Retrieved 7 April 2011.
  15. ^ Starkey J (August 2, 2011). "AstraZeneca (finally) lands name for cancer drug". Delaware Inc.
  16. ^ Fourcade M (27 July 2015). "Sanofi to Buy Caprelsa Drug from AstraZeneca for $300 Million". Bloomberg.
  17. ^ "Zactima". European Medicines Agency. 17 September 2018.
  18. S2CID 46676794
    .

External links

  • "Vandetanib". Drug Information Portal. U.S. National Library of Medicine.
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