Vismodegib

Vismodegib
Names
PronunciationVismodegib /ˌvɪsmoʊˈdɛɡɪb/ VIS-moh-DEG-ib
Erivedge /ˈɛrɪvɛdʒ/ ERR-i-vej
Trade namesErivedge
Other namesGDC-0449, RG-3616
IUPAC name
  • 2-Chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide
Clinical data
Drug classHedgehog pathway inhibitor[1]
Main usesBasal-cell cancer (BCC)[2]
Side effectsHair loss, tiredness, nausea, muscle spasms[2]
InteractionsSt John’s wort[3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: X (High risk)[4]
  • US: X (Contraindicated)[4]
    Routes of
    use    		By mouth (capsules)
    Typical dose150 mg once daily[1]
    External links
    AHFS/Drugs.comMonograph
    Legal
    License data
    Legal status
    Pharmacokinetics
    Bioavailability31.8%
    Protein binding>99%
    Metabolism<2% metabolised by CYP2C9, CYP3A4, CYP3A5
    Elimination half-life4 days (continuous use),
    12 days (single dose)
    ExcretionFecal (82%), Urinary (4.4%)
    Chemical and physical data
    FormulaC19H14Cl2N2O3S
    Molar mass421.29 g·mol−1
    3D model (JSmol)
    SMILES
    • CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl
    InChI
    • InChI=1S/C19H14Cl2N2O3S/c1-27(25,26)13-6-7-14(17(21)11-13)19(24)23-12-5-8-16(20)15(10-12)18-4-2-3-9-22-18/h2-11H,1H3,(H,23,24)
    • Key:BPQMGSKTAYIVFO-UHFFFAOYSA-N

    Vismodegib, sold under the brand name Erivedge, is a medication used to treat basal-cell cancer (BCC).[2] Specifically it is used in those in who the cancer has spread or has recurred and cannot be treated by other methods.[2] It is taken by mouth.[2]

    Common side effects include hair loss, tiredness, nausea, and muscle spasms.[2] Use during pregnancy may harm the baby.[2] Effective birth control is recommended for both men and women.[2] It is a hedgehog pathway inhibitor.[1]

    Vismodegib was approved for medical use in the United States in 2012 and Europe in 2013.[2][3] In the United States it costs about 12,300 USD per month as of 2021 and is only available through specialty pharmacies.[2][5] In the United Kingdom this amount costs the NHS about £6,300.[1]

    Medical uses

    Vismodegib is used for people with basal cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.[6][7]

    Such use; however, is not recommended in the United Kingdom by NICE since 2017.[1]

    Dosage

    It is taken at a dose of 150 mg once per day.[1]

    Side effects

    Common side effects included gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation), muscle spasms, fatigue, hair loss, and dysgeusia (distortion of the sense of taste). The effects were mostly mild to moderate.[4]

    Mechanism of action

    The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway.[8] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.[9] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.[10]

    History

    It was the first Hedgehog signaling pathway targeting agent to gain US approval.[6] It was developed by the biotechnology/pharmaceutical company Genentech.[6]

    Research

    The drug is also undergoing trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma as of June 2011.[8]

    See also

    • Cyclopamine, a naturally occurring SMO antagonist

    References

    1. 1 2 3 4 5 6 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 1066. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
    2. 1 2 3 4 5 6 7 8 9 10 "Vismodegib Monograph for Professionals". Drugs.com. Archived from the original on 22 March 2016. Retrieved 15 September 2021.
    3. 1 2 "Erivedge". Archived from the original on 13 August 2021. Retrieved 16 September 2021.
    4. 1 2 3 FDA Professional Drug Information
    5. ↑ "Erivedge Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 5 September 2015. Retrieved 16 September 2021.
    6. 1 2 3 "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma". Roche. 30 January 2012. Archived from the original on 9 August 2020. Retrieved 9 August 2020.
    7. ↑ Lacroix M (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7. Archived from the original on 2015-06-26. Retrieved 2021-01-06.
    8. 1 2 "Molecule of the Month". June 2011. Archived from the original on 2011-09-27. Retrieved 2021-01-06. {{cite journal}}: Cite journal requires |journal= (help)
    9. ↑ "Vismodegib (GDC-0449) Smoothened Inhibitor - BioOncology". Archived from the original on 2012-02-02. Retrieved 2021-01-06.
    10. ↑ Spreitzer H (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.{{cite journal}}: CS1 maint: unrecognized language (link)
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