Histrelin

Histrelin
Names
Trade namesVantas, Supprelin LA, others
Other namesHistrelin acetate
IUPAC name
  • 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-1-benzyl-D-histidyl-L-leucyl-N5-(diaminomethylene)-L-ornithyl-N-ethyl-L-prolinamide
Clinical data
Drug classGnRH agonist; Antigonadotropin
Main usesProstate cancer[1]
Side effectsPain at the site of injection, hot flashes, breast enlargement, sexual dysfunction, tiredness, kidney problems, constipation, weight loss, trouble sleeping[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: X (Contraindicated)
    Routes of
    use    		Subcutaneous implant
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa601146
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability92%
    Protein binding70%
    MetabolismLiver
    Elimination half-life4.0 hours
    Chemical and physical data
    FormulaC66H86N18O12
    Molar mass1323.528 g·mol−1
    3D model (JSmol)
    SMILES
    • CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CN(C=N2)CC3=CC=CC=C3)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@H](CC7=CNC=N7)NC(=O)[C@@H]8CCC(=O)N8
    InChI
    • InChI=1S/C66H86N18O12/c1-4-70-64(95)55-17-11-25-84(55)65(96)48(16-10-24-71-66(67)68)76-58(89)49(26-38(2)3)77-62(93)53(30-43-34-83(37-74-43)33-40-12-6-5-7-13-40)81-59(90)50(27-39-18-20-44(86)21-19-39)78-63(94)54(35-85)82-60(91)51(28-41-31-72-46-15-9-8-14-45(41)46)79-61(92)52(29-42-32-69-36-73-42)80-57(88)47-22-23-56(87)75-47/h5-9,12-15,18-21,31-32,34,36-38,47-55,72,85-86H,4,10-11,16-17,22-30,33,35H2,1-3H3,(H,69,73)(H,70,95)(H,75,87)(H,76,89)(H,77,93)(H,78,94)(H,79,92)(H,80,88)(H,81,90)(H,82,91)(H4,67,68,71)/t47-,48-,49-,50-,51-,52-,53+,54-,55-/m0/s1 checkY
    • Key:HHXHVIJIIXKSOE-QILQGKCVSA-N checkY

    Histrelin, sold under the brand names Vantas among others, is a medication used to treat advanced prostate cancer.[1] It may also be used for precocious puberty and in transgender children.[2][3] It is given by injection under the skin.[1]

    Common side effects include pain at the site of injection, hot flashes, breast enlargement, sexual dysfunction, tiredness, kidney problems, constipation, weight loss, and trouble sleeping.[1] Other side effects may include osteoporosis, high blood sugar, liver problems, anaphylaxis, and pituitary apoplexy.[1] Use in pregnancy may harm the baby.[1] It acts similar to gonadotropin-releasing hormone (GnRH), resulting in increased luteinizing hormone (LH) and follicle stimulating hormone (FSH), and therefore decreased testosterone and estrogen.[1][3]

    Histrelin was approved for medical use in the United States in 1991.[1] It is available as a generic medication.[3] In the United States an implant costs about 5,100 USD per year as of 2021.[4] Since 2014 it is no longer commercially available in the United Kingdom.[5]

    Medical uses

    Histrelin is used to treat hormone-sensitive cancers of the prostate in men and uterine fibroids in women. In addition, histrelin has been proven to be highly effective in treating central precocious puberty in children.[6][7]

    Histrelin can be part of the primary care protocol in transgender children/youth, which is an off-label use in the USA[2] and the UK,[8] and is used in suppressing cis-sex puberty, until the patient is ready to begin cross-sex hormonal therapy. It is also sometimes prescribed to transgender adults who benefit from having their sex hormone production halted.

    Dosage

    It is often used as a 50 mg implant, once per year.[1]

    It is available as a daily intramuscular injection. Histrelin is also available in a 12-month subcutaneous implant (Vantas) for the palliative treatment of advanced prostate cancer, since 2005 in the US, and since Jan 2010 in the UK. A 12-month subcutaneous implant (Supprelin LA) for central precocious puberty (CPP) was approved on May 3, 2007 by the U.S. Food and Drug Administration.

    Side effects

    Side effects are mainly due to low testosterone levels and include headache, hot flashes, reduced libido, and erectile dysfunction.[9]

    Pharmacology

    It acts on particular cells of the pituitary gland called gonadotropes. Histrelin stimulates these cells to release luteinizing hormone and follicle-stimulating hormone. Thus it is considered a gonadotropin-releasing hormone agonist or GnRH agonist.

    In a process known as downregulation, daily stimulation of pituitary gonadotropes causes them to become desensitized to the effects of histrelin. As a consequence, levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) fall after a short period of time. From that point forward, as long as histrelin is administered, the levels of LH and FSH in the blood remain low.[10][11]

    This prolonged lowering of LH and FSH levels is the rationale for therapy using GnRH agonists. Since LH and FSH stimulate the gonads to produce estrogens and androgens in females and males respectively, histrelin can effectively be used to decrease the sex steroids in the blood of patients.

    Cost

    In the United States a 50 mg implant for prostate cancer costs about 5,100 USD per year as of 2021.[4] The implant for precocious puberty, despite being the same 50 mg dose costs about 45,000 USD as of 2021.[12] The first medication releases 50 micrograms per day while the second releases 65 micrograms per day, which is likely of no importance.[13]

    References

    1. 1 2 3 4 5 6 7 8 9 10 "Histrelin Monograph for Professionals". Drugs.com. Archived from the original on 29 August 2019. Retrieved 10 December 2021.
    2. 1 2 "Primary Care Protocol for Transgender Patient Care: Hormone Administration". transhealth.ucsf.edu. Archived from the original on 2012-01-17. Retrieved 2015-09-29.
    3. 1 2 3 "Histrelin". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 11 December 2021. Retrieved 10 December 2021.
    4. 1 2 "Vantas Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 22 July 2021. Retrieved 10 December 2021.
    5. ↑ "Vantas (discontinued in the UK - September 2014)". Netdoctor. 28 September 2012. Archived from the original on 4 November 2021. Retrieved 10 December 2021.
    6. ↑ "Histrelin consumer information". Archived from the original on 2009-06-04. Retrieved 2021-08-23.
    7. ↑ Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, Reiter EO, et al. (May 2007). "Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial". The Journal of Clinical Endocrinology and Metabolism. 92 (5): 1697–704. doi:10.1210/jc.2006-2479. PMID 17327379. Archived from the original on 2011-05-16. Retrieved 2021-08-23.
    8. ↑ Cohen, Deborah; Barnes, Hannah (20 September 2019). "Gender dysphoria in children: puberty blockers study draws further criticism". BMJ. 366: l5647. doi:10.1136/bmj.l5647. PMID 31540909. S2CID 202711942. Archived from the original on 17 January 2021. Retrieved 3 February 2021.
    9. ↑ Drugs.com: Histrelin Monograph
    10. ↑ Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 372–3. ISBN 3-8047-1763-2.{{cite book}}: CS1 maint: unrecognized language (link)
    11. ↑ Wuttke W, Jarry H, Feleder C, Moguilevsky J, Leonhardt S, Seong JY, Kim K (1996). "The neurochemistry of the GnRH pulse generator". Acta Neurobiologiae Experimentalis. 56 (3): 707–13. PMID 8917899. Archived from the original on 2015-12-08. Retrieved 2021-08-23.
    12. ↑ "Supprelin LA Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 20 April 2021. Retrieved 10 December 2021.
    13. ↑ "Hormone Blocker Sticker Shock: Kids Drug Costs 8 Times More Than One For Adults". NPR.org. Archived from the original on 3 December 2021. Retrieved 10 December 2021.
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