Degarelix

Last updated

Degarelix
Degarelix.svg
Clinical data
Trade names Firmagon, others
Other namesFE-200486
AHFS/Drugs.com Monograph
MedlinePlus a609022
License data
Pregnancy
category
Routes of
administration 		Subcutaneous injection
Drug class GnRH analogue; GnRH antagonist; Antigonadotropin
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only) [2]
  • US: ℞-only [3]
  • EU:Rx-only [4]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 30–40%
Protein binding ~90%
Metabolism Subject to common peptidic degradation during passage through the hepato-biliary system; not a substrate for the human CYP450 system
Elimination half-life 23–61 days
Excretion Feces: 70–80%
Urine: 20–30%
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard 100.234.843 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C82H103ClN18O16
Molar mass 1632.29 g·mol−1
3D model (JSmol)
  • C[C@H](C(=O)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCNC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc2ccc(cc2)NC(=O)N)NC(=O)[C@H](Cc3ccc(cc3)NC(=O)[C@@H]4CC(=O)NC(=O)N4)NC(=O)[C@H](CO)NC(=O)[C@@H](Cc5cccnc5)NC(=O)[C@@H](Cc6ccc(cc6)Cl)NC(=O)[C@@H](Cc7ccc8ccccc8c7)NC(=O)C
  • InChI=1S/C82H103ClN18O16/c1-45(2)35-60(72(107)92-59(16-9-10-33-87-46(3)4)80(115)101-34-12-17-68(101)79(114)88-47(5)70(84)105)93-74(109)63(38-51-23-30-58(31-24-51)91-81(85)116)95-76(111)64(39-50-21-28-57(29-22-50)90-71(106)66-42-69(104)100-82(117)99-66)97-78(113)67(44-102)98-77(112)65(41-53-13-11-32-86-43-53)96-75(110)62(37-49-19-26-56(83)27-20-49)94-73(108)61(89-48(6)103)40-52-18-25-54-14-7-8-15-55(54)36-52/h7-8,11,13-15,18-32,36,43,45-47,59-68,87,102H,9-10,12,16-17,33-35,37-42,44H2,1-6H3,(H2,84,105)(H,88,114)(H,89,103)(H,90,106)(H,92,107)(H,93,109)(H,94,108)(H,95,111)(H,96,110)(H,97,113)(H,98,112)(H3,85,91,116)(H2,99,100,104,117)/t47-,59+,60+,61-,62-,63-,64+,65-,66+,67+,68+/m1/s1 X mark.svgN
  • Key:MEUCPCLKGZSHTA-XYAYPHGZSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Degarelix, sold under the brand name Firmagon among others, is a hormonal therapy used in the treatment of prostate cancer. [3] [5]

Contents

Testosterone is a male hormone that promotes growth of many prostate tumours and therefore reducing circulating testosterone to very low (castration) levels is often the treatment goal in the management of advanced prostate cancer. Degarelix has an immediate onset of action, binding to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and blocking their interaction with GnRH. This induces a fast and profound reduction in luteinizing hormone (LH), follicle-stimulating hormone (FSH) and in turn, testosterone suppression. [6]

Medical uses

The GnRH antagonist degarelix, through its ability to reduce serum testosterone, is used to treat hormone-sensitive prostate cancer. [7]

Side effects

Degarelix is commonly associated with hormonal side effects such as hot flashes and weight gain. [7] [8] [9] Due to its mode of administration (subcutaneous injection), degarelix is also associated with injection-site reactions such as injection-site pain, erythema or swelling. Injection-site reactions are usually mild or moderate in intensity and occur predominantly after the first dose, decreasing in frequency thereafter. [7] Less common: Anemia. Diarrhea, nausea. Hyperhidrosis including night sweats, rash. Gynecomastia, testicular atrophy, erectile dysfunction. Increased transaminases. Musculoskeletal pain and discomfort. Dizziness, headache. Insomnia. Weight gain. Chills, fever, fatigue, flu-like illness. [10]

Pharmacology

Testosterone levels during the first month of androgen deprivation therapy in men with prostate cancer treated with subcutaneous injections of the GnRH antagonist degarelix (240 then 80 mg/month or the GnRH agonist leuprorelin (7.5 mg/month). Testosterone levels in men with prostate cancer treated with GnRH agonists and antagonists.png
Testosterone levels during the first month of androgen deprivation therapy in men with prostate cancer treated with subcutaneous injections of the GnRH antagonist degarelix (240 then 80 mg/month or the GnRH agonist leuprorelin (7.5 mg/month).

GnRH antagonists (receptor blockers) such as degarelix are synthetic peptide derivatives of the natural GnRH decapeptide – a hormone that is made by neurons in the hypothalamus. GnRH antagonists compete with natural GnRH for binding to GnRH receptors in the pituitary gland. This reversible binding blocks the release of LH and FSH from the pituitary. The reduction in LH subsequently leads to a rapid and sustained suppression of testosterone release from the testes and subsequently reduces the size and growth of the prostate cancer. This in turn results in a reduction in prostate-specific antigen (PSA) levels in the patient's blood. Measuring PSA levels helps to monitor how patients with prostate cancer are responding to treatment.[ medical citation needed ]

Unlike GnRH agonists, which cause an initial stimulation of the hypothalamic-pituitary-gonadal axis (HPGA), leading to a surge in testosterone levels, and under certain circumstances, a flare-up of the tumour, GnRH antagonists do not cause a surge in testosterone or clinical flare. [12] Clinical flare is a phenomenon that occurs in patients with advanced disease, which can precipitate a range of clinical symptoms such as bone pain, urethral obstruction, and spinal cord compression. Drug agencies have issued boxed warnings regarding this phenomenon in the prescribing information for GnRH agonists. As testosterone surge does not occur with GnRH antagonists, there is no need for patients to receive an antiandrogen as flare protection during prostate cancer treatment. GnRH agonists also induce an increase in testosterone levels after each reinjection of the drug – a phenomenon that does not occur with GnRH antagonists such as degarelix.[ medical citation needed ]

GnRH antagonists have an immediate onset of action leading to a fast and profound suppression of testosterone and are therefore especially valuable in the treatment of patients with prostate cancer where fast control of disease is needed.[ medical citation needed ]

History

In December 2008, the US Food and Drug Administration (FDA) approved degarelix for the treatment of people with advanced prostate cancer. [13] [14] It was subsequently approved by the European Commission at the recommendation of the European Medicines Agency (EMA) in February 2009, for use in adult males with advanced, hormone-dependent prostate cancer. [4] Ferring Pharmaceuticals markets the drug under the name Firmagon. [4]

Research

Degarelix is studied for use as a chemical castration agent on men with pedophilia in Sweden. [15] A study demonstrated a reduced the risk score for committing child sexual abuse in men with pedophilic disorder two weeks after initial injection. [16]

See also

Related Research Articles

<span class="mw-page-title-main">Gonadotropin-releasing hormone</span> Mammalian protein found in Homo sapiens

Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released from GnRH neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.

<span class="mw-page-title-main">Goserelin</span> Chemical compound

Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones, particularly in the treatment of breast and prostate cancer. It is an injectable gonadotropin releasing hormone agonist.

<span class="mw-page-title-main">Abarelix</span> Chemical compound

Abarelix, sold under the brand name Plenaxis, is an injectable gonadotropin-releasing hormone antagonist which is marketed in Germany and the Netherlands. It is primarily used in oncology to reduce the amount of testosterone made in patients with advanced symptomatic prostate cancer for which no other treatment options are available.

<span class="mw-page-title-main">Gonadorelin</span> Chemical compound

Gonadorelin is a gonadotropin-releasing hormone agonist which is used in fertility medicine and to treat amenorrhea and hypogonadism. It is also used in veterinary medicine. The medication is a form of the endogenous GnRH and is identical to it in chemical structure. It is given by injection into a blood vessel or fat or as a nasal spray.

<span class="mw-page-title-main">Nafarelin</span> Pharmaceutical drug

Nafarelin, sold under the brand name Synarel among others, is a gonadotropin-releasing hormone agonist medication which is used in the treatment of endometriosis and early puberty. It is also used to treat uterine fibroids, to control ovarian stimulation in in vitro fertilization (IVF), and as part of transgender hormone therapy. The medication is used as a nasal spray two to three times per day.

<span class="mw-page-title-main">Buserelin</span> Chemical compound

Buserelin, sold under the brand name Suprefact among others, is a medication which is used primarily in the treatment of prostate cancer and endometriosis. It is also used for other indications such as the treatment of premenopausal breast cancer, uterine fibroids, and early puberty, in assisted reproduction for female infertility, and as a part of transgender hormone therapy. In addition, buserelin is used in veterinary medicine. The medication is typically used as a nasal spray three times per day, but is also available for use as a solution or implant for injection into fat.

<span class="mw-page-title-main">Flutamide</span> Chemical compound

Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair growth, and high androgen levels in women. It is taken by mouth, usually three times per day.

<span class="mw-page-title-main">Triptorelin</span> GnRH-agonist

Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

<span class="mw-page-title-main">Gonadotropin-releasing hormone agonist</span> Drug class affecting sex hormones

A gonadotropin-releasing hormone agonist is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatment of hormone-sensitive cancers such as prostate cancer and breast cancer, certain gynecological disorders like heavy periods and endometriosis, high testosterone levels in women, early puberty in children, as a part of transgender hormone therapy, and to delay puberty in transgender youth among other uses. It is also used in the suppression of spontaneous ovulation as part of controlled ovarian hyperstimulation, an essential component in IVF. GnRH agonists are given by injections into fat, as implants placed into fat, and as nasal sprays.

<span class="mw-page-title-main">Gonadotropin-releasing hormone antagonist</span> Class of medications

Gonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.

The gonadotropin-releasing hormone receptor (GnRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is the receptor of gonadotropin-releasing hormone (GnRH). The GnRHR is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate.

<span class="mw-page-title-main">Histrelin</span> Chemical compound

Histrelin acetate, sold under the brand names Vantas and Supprelin LA among others, is a nonapeptide analogue of gonadotropin-releasing hormone (GnRH) with added potency. When present in the bloodstream, 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.

<span class="mw-page-title-main">Ganirelix</span> Pharmaceutical drug

Ganirelix acetate, sold under the brand names Orgalutran and Antagon among others, is an injectable competitive gonadotropin-releasing hormone antagonist. It is primarily used in assisted reproduction to control ovulation. The drug works by blocking the action of gonadotropin-releasing hormone (GnRH) upon the pituitary, thus rapidly suppressing the production and action of LH and FSH. Ganirelix is used in fertility treatment to prevent premature ovulation that could result in the harvesting of eggs that are too immature to be used in procedures such as in vitro fertilization.

<span class="mw-page-title-main">Cetrorelix</span> Drug used in IVF procedures

Cetrorelix, or cetrorelix acetate, sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) antagonist. A synthetic decapeptide, it is used in assisted reproduction to inhibit premature luteinizing hormone surges The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, cetrorelix can be used to treat hormone-sensitive cancers of the prostate and breast and some benign gynaecological disorders. It is administered as either multiple 0.25 mg daily subcutaneous injections or as a single-dose 3 mg subcutaneous injection. The duration of the 3 mg single dose is four days; if human chorionic gonadotropin (hCG) is not administered within four days, a daily 0.25 mg dose is started and continued until hCG is administered.

Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology, others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

<span class="mw-page-title-main">Deslorelin</span> Chemical compound

Deslorelin, sold under the brand names Ovuplant, SucroMate, and Suprelorin among others, is an injectable gonadotropin releasing hormone superagonist which is used in veterinary medicine for various indications.

<span class="mw-page-title-main">Relugolix</span> Chemical compound

Relugolix, sold under the brand names Orgovyx and Relumina among others, is a gonadotropin-releasing hormone antagonist medication which is used in the treatment of prostate cancer in men and uterine fibroids in women. It is also under development for use in the treatment of endometriosis. It is taken by mouth once per day.

<span class="mw-page-title-main">Pharmacology of bicalutamide</span>

The pharmacology of bicalutamide is the study of the pharmacodynamic and pharmacokinetic properties of the nonsteroidal antiandrogen (NSAA) bicalutamide. In terms of pharmacodynamics, bicalutamide acts as a selective antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). It has no capacity to activate the AR. It does not decrease androgen levels and has no other important hormonal activity. The medication has progonadotropic effects due to its AR antagonist activity and can increase androgen, estrogen, and neurosteroid production and levels. This results in a variety of differences of bicalutamide monotherapy compared to surgical and medical castration, such as indirect estrogenic effects and associated benefits like preservation of sexual function and drawbacks like gynecomastia. Bicalutamide can paradoxically stimulate late-stage prostate cancer due to accumulated mutations in the cancer. When used as a monotherapy, bicalutamide can induce breast development in males due to its estrogenic effects. Unlike other kinds of antiandrogens, it may have less adverse effect on the testes and fertility.

Drugs and sexual desire is about sexual desire being manipulated through drugs from various approaches. Sexual desire is generated under the effects from sex hormones and microcircuits from brain regions. Neurotransmitters play essential roles in stimulating and inhibiting the processes that lead to libido production in both men and women. For instance, a positive stimulation is modulated by dopamine from the medial preoptic area in the hypothalamus and norepinephrine. At the same time, inhibition occurs when prolactin and serotonin are released for action.

References

  1. 1 2 "Degarelix (Firmagon) Use During Pregnancy". Drugs.com. 3 February 2020. Archived from the original on 26 February 2020. Retrieved 25 February 2020.
  2. ↑ "Firmagon 120mg Injection - Summary of Product Characteristics (SmPC)". (emc). 15 January 2020. Archived from the original on 26 February 2020. Retrieved 25 February 2020.
  3. 1 2 "Firmagon- degarelix kit". DailyMed. 18 September 2019. Archived from the original on 12 August 2020. Retrieved 26 February 2020.
  4. 1 2 3 "Firmagon EPAR". European Medicines Agency (EMA). 10 January 2020. Archived from the original on 26 February 2020. Retrieved 25 February 2020.
  5. ↑ "Degarelix Acetate Monograph for Professionals". Drugs.com. 7 October 2019. Archived from the original on 26 February 2020. Retrieved 25 February 2020.
  6. ↑ Princivalle M, Broqua P, White R, Meyer J, Mayer G, Elliott L, et al. (March 2007). "Rapid suppression of plasma testosterone levels and tumor growth in the dunning rat model treated with degarelix, a new gonadotropin-releasing hormone antagonist". The Journal of Pharmacology and Experimental Therapeutics. 320 (3): 1113–8. doi:10.1124/jpet.106.112326. PMID   17179469. S2CID   2892725.
  7. 1 2 3 Clinton TN, Woldu SL, Raj GV (June 2017). "Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer". Expert Opinion on Pharmacotherapy. 18 (8): 825–832. doi:10.1080/14656566.2017.1328056. PMC   7171911 . PMID   28480768.
  8. ↑ Gittelman M, Pommerville PJ, Persson BE, Jensen JK, Olesen TK (November 2008). "A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America". The Journal of Urology. 180 (5): 1986–92. doi:10.1016/j.juro.2008.07.033. PMID   18801505.
  9. ↑ Van Poppel H, Tombal B, de la Rosette JJ, Persson BE, Jensen JK, Kold Olesen T (October 2008). "Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer". European Urology. 54 (4): 805–13. doi:10.1016/j.eururo.2008.04.065. PMID   18538469.
  10. ↑ "Firmagon "Ferring Pharmaceuticals A/S" - Felleskatalogen". www.felleskatalogen.no. Archived from the original on 28 November 2020. Retrieved 5 May 2020.
  11. ↑ Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, et al. (December 2008). "The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer". BJU Int. 102 (11): 1531–8. doi:10.1111/j.1464-410X.2008.08183.x. PMID   19035858. S2CID   8280692.
  12. ↑ van Poppel H, Nilsson S (June 2008). "Testosterone surge: rationale for gonadotropin-releasing hormone blockers?". Urology. 71 (6): 1001–6. doi:10.1016/j.urology.2007.12.070. PMID   18407326.
  13. ↑ "Drug Approval Package: Degarelix NDA #022201". U.S. Food and Drug Administration (FDA). Archived from the original on 9 August 2020. Retrieved 29 September 2020.
  14. ↑ "FDA Approves Ferring Pharmaceuticals' Degarelix (Generic Name) for Treatment of Advanced Prostate Cancer" (Press release). Ferring Pharmaceuticals. 24 December 2008. Archived from the original on 8 June 2011. Retrieved 25 February 2020– via PR Newswire.
  15. ↑ "Pedofiler ska stoppas – med kemisk kastrering". Expressen. Archived from the original on 26 February 2021. Retrieved 4 August 2016.
  16. ↑ Landgren V, Malki K, Bottai M, Arver S, Rahm C (April 2020). "Effect of Gonadotropin-Releasing Hormone Antagonist on Risk of Committing Child Sexual Abuse in Men With Pedophilic Disorder: A Randomized Clinical Trial". JAMA Psychiatry. 77 (9): 897–905. doi:10.1001/jamapsychiatry.2020.0440. PMC   7191435 . PMID   32347899.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.