Degarelix
Firmagon, FE200486, degarelix acetate
1What it is
Degarelix is a GnRH antagonist — a competitive blocker of the receptor, rather than an over-stimulating . First- and second-generation antagonists caused histamine release and were unusable; degarelix, developed by Ferring, solved that with a heavily modified decapeptide that forms a gel depot under the skin and releases slowly over a month. It is approved for advanced hormone-dependent prostate cancer. Its practical advantage over agonists is speed and the absence of the testosterone flare: no anti-androgen cover is needed and castrate levels are reached in about three days rather than three to four weeks.
It has no community or self-directed use.
2How it's thought to work
Degarelix occupies the GnRH receptor without activating it. Pituitary release of LH and FSH stops almost immediately; testicular testosterone production falls to castrate range in 96% of men by day 3. FSH is suppressed more deeply than with , which may matter for prostate tissue that expresses FSH receptors. Because there is no receptor down-regulation, suppression is maintained only while drug is present, and testosterone recovers relatively quickly after stopping.
3What the research shows
Testosterone suppression versus leuprolide (CS21)
Cardiovascular safety versus agonists
Intermittent and neoadjuvant use, 3-monthly formulation
Lower urinary tract symptoms, benign prostatic hyperplasia
4Reported side effects and interactions
Literature-reported
injection-site reactions are the dominant adverse effect — pain, erythema, swelling, nodules — in roughly 35–40% of men, mostly after the larger loading injections and far more often than with ; hot flushes (~25%); weight gain; fatigue; raised liver transaminases (mostly mild and transient); chills and fever occasionally after injection. Class-level effects of androgen deprivation apply: loss of libido, erectile dysfunction, gynaecomastia, bone loss, anaemia, insulin resistance, QT prolongation. Hypersensitivity, including anaphylaxis, is rare.Community-reported
essentially none documented.Theoretical. deeper FSH suppression than agonists has unknown long-term consequences.
Interactions. no cytochrome P450 interactions identified; additive QT-prolonging risk with class IA/III antiarrhythmics and other QT-prolonging drugs.
Markers researchers commonly monitor
From the label and prostate-cancer guidelines:
| Marker | Why it's watched |
|---|---|
| Testosterone | confirms castrate suppression; particularly useful with degarelix because suppression depends on continuous drug presence. |
| PSA | tumour response; rising PSA under castrate testosterone defines castration resistance. |
| Liver enzymes (ALT/AST) | transient elevations occur; the label advises monitoring in men with liver impairment. |
| ECG (QTc), electrolytes | in men with cardiac history or on QT-prolonging drugs. |
| Bone mineral density, HbA1c, lipid panel, haemoglobin | long-term androgen-deprivation effects. |
| Injection sites | nodules and erythema are common and worth documenting. |
Free for everyone. Safety information is never behind a paywall.
5Reconstitution and handling
Supplied as a kit of 120 mg or 80 mg powder vials with pre-filled solvent syringes. at the bedside by a clinician to 40 mg/mL for the loading dose and 20 mg/mL for maintenance, swirled (not shaken) and injected deep subcutaneously into the abdomen within one hour; the gel depot forms on contact with tissue. Not a self-administered or home-reconstituted product; the calculator is not applicable.
6Commonly studied alongside
Leuprolide (the standard comparator; see GnRH analogue profiles #102–#108), goserelin (#212), buserelin (#211), relugolix (the oral non-peptide GnRH antagonist that is its main competitor), abiraterone and enzalutamide (added for castration-resistant disease), radiotherapy.
Informational cross-links. Not stack recommendations.
7Regulatory status by region
| Region | Status (checked —) |
|---|---|
| United States | FDA-approved (December 2008) for advanced prostate cancer |
| European Union | EMA-authorised (February 2009) for advanced hormone-dependent prostate cancer; 3-monthly formulation authorised in some markets † |
| United Kingdom | MHRA-licensed; prescription-only |
| Australia | TGA-registered; PBS-listed |
| South Africa | SAHPRA registration † |
| Sport (WADA) | Not named on the Prohibited List; GnRH antagonists are not listed under S2 (which covers releasing factors, i.e. agonists) † |
8Open questions
- Does antagonist therapy genuinely reduce cardiovascular events compared with in men with heart disease? PRONOUNCE was underpowered.
- Whether deeper FSH suppression translates into any oncological benefit.
- Head-to-head comparison with oral relugolix on tolerability and outcomes.
9References
- 1Klotz L et al. (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. PubMed
- 2Crawford ED et al. (2011). A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer. J Urol. PubMed · DOI
- 3Albertsen PC et al. (2014). Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol. PubMed · DOI
- 4Lopes RD et al. (2021). Cardiovascular safety of degarelix versus leuprolide in patients with prostate cancer: the primary results of the PRONOUNCE randomized trial. Circulation. PubMed · DOI
- 5Firmagon (degarelix) US prescribing information and EMA Summary of Product Characteristics (current). PubMed
References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.
† Being confirmed by our reviewers against current sources.
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Self-reported side effects Phase 2
11Page history
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