An independent peptide reference — no sellers, every claim sourced

Degarelix

Also known as Firmagon, FE200486, degarelix acetate

GnRH receptor antagonist for prostate cancer: castrate testosterone within days, with no agonist flare.

clinically proven Hormonal & sexual approved drug

At a glance

Category
Hormonal & sexual
Status
approved drug
Made from
synthetic Chemically synthesised decapeptide, supplied as the acetate salt 1.
Route
subcutaneous injection into the abdomen only, given by a healthcare professional
Half-life
a median terminal half-life of approximately 53 days after subcutaneous administration — not a property of the molecule but of the depot, since degarelix gels at the injection site and is released from it very slowly 1
Onset
very fast, and this is the point of the drug: 52% of patients were below the castrate testosterone threshold of 50 ng/dL by day 1 and 96% by day 3, against 0% on leuprolide at both timepoints 1
Molecular weight
1632.3 daltons; empirical formula C82H103N18O16Cl 1
Sequence
A synthetic linear decapeptide amide containing seven unnatural amino acids, five of them D-amino acids

Prescription-only medicine, administered by a healthcare professional. Approved by the FDA on 24 December 2008 under NDA 022201 for advanced prostate cancer 51. The EU marketing authorisation was issued on 17 February 2009 and is broader: advanced hormone-dependent prostate cancer, and high-risk localised or locally advanced hormone-dependent disease before or together with radiotherapy 2.

Doping status: Not listed by WADA — GnRH agonists are prohibited in males under S2.2.1, but the antagonists are not named and do not stimulate testosterone

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Degarelix binds reversibly and competitively to pituitary GnRH receptors, reducing the release of luteinising hormone and follicle-stimulating hormone and therefore of testosterone 1. That is the whole mechanism, and its simplicity is what distinguishes it from the drugs it replaced.

The contrast with the GnRH agonists is the reason this compound exists. Leuprolide, triptorelin, goserelin and nafarelin are agonists: they occupy the same receptor but activate it. Continuous rather than pulsatile stimulation eventually desensitises and downregulates the gonadotroph, which is where the therapeutic suppression comes from — but before that happens the receptor is being driven hard, and LH, FSH and testosterone all surge. That surge is the 'flare', and in prostate cancer it is not a curiosity: a testosterone spike in a man with bony metastases or a tumour near the spinal cord can worsen bone pain, precipitate cord compression or cause urinary obstruction, which is why agonist therapy is conventionally covered with an antiandrogen for the first weeks. An antagonist has no agonist phase to get through. Blockade begins with the first injection and testosterone falls immediately.

The registration trial quantified this precisely. Testosterone was measured on days 0, 1, 3, 7, 14 and 28. On degarelix, 52% of patients were at or below 50 ng/dL by day 1, 96% by day 3, 99% by day 7 and 100% by day 28. On leuprolide the figures were 0%, 0%, 1%, 18% and 100% 1. By day 28 the two drugs are equivalent — 97.2% versus 96.4% castration rates maintained from day 28 to day 364 1 — so the difference is entirely in the first month, and it is total.

The same logic makes cetrorelix and ganirelix useful in assisted reproduction: an antagonist can be introduced mid-cycle to block a premature LH surge without first provoking one, which an agonist cannot do. Degarelix is the oncology member of the same family, differing mainly in that it is formulated to form a subcutaneous gel depot lasting a month rather than to act over hours.

That depot is also the source of the drug's main practical drawback. Degarelix is reconstituted immediately before use and injected as a solution that gels under the skin, from which the peptide is released over 28 days — hence the 53-day terminal half-life, which reflects release rather than elimination 1. Injection site reactions occurred in 35% of degarelix patients against under 1% of those on intramuscular leuprolide 1. Elimination itself is by peptide hydrolysis during hepatobiliary passage, with 70-80% excreted via the hepatobiliary route and 20-30% renally; degarelix is not a substrate, inducer or inhibitor of CYP450 or P-glycoprotein 1.

What the research shows

The evidence for the drug's central claim — immediate testosterone suppression without a flare — is direct, quantitative and from a randomised comparison against an agonist. The evidence that this translates into better cancer outcomes is much weaker: the pivotal trial's endpoint was a testosterone threshold, not survival. Whether antagonists carry a lower cardiovascular risk than agonists remains genuinely unresolved.

Research in humans

The pivotal trial (NCT00295750) was an open-label, multicentre, randomised, parallel-group study in 620 men with prostate cancer, median age 73, comparing degarelix 240 mg then 80 mg monthly against leuprolide 7.5 mg intramuscularly monthly for 12 months 13. The primary objective was achieving and maintaining testosterone at or below 50 ng/dL from day 28 to day 364: 97.2% on degarelix (95% CI 93.5 to 98.8) against 96.4% on leuprolide (92.5 to 98.2) 1. Within the first 28 days the divergence was complete, as set out above. PSA fell 64% at two weeks, 85% at one month and 95% at three months, though the label cautions that this should be read carefully given the heterogeneity of the population and that no evidence shows the speed of PSA decline relates to clinical benefit 1. A 5-year extension in 385 patients, with a crossover arm from leuprolide, reported a median treatment duration of about 43 months 14.

Animal and lab research

Two-year subcutaneous carcinogenicity studies were conducted in both species. In rats, 25 mg/kg every two weeks increased the combined incidence of benign haemangiomas and malignant haemangiosarcomas in females; in mice there was no statistically significant increase in tumour incidence at any dose 1. Degarelix did not cause genetic damage in bacterial mutation, human lymphocyte chromosome aberration or rodent bone marrow micronucleus assays 1. Single doses caused reversible infertility in male rats at about 5% of the clinical loading dose on a body surface area basis, and reduced fertility in female rats at about 0.5% 1.

Caveats. The pivotal trial was open-label, which is defensible given the different routes and schedules but is still a limitation. Its endpoint was a biochemical castration threshold rather than progression, metastasis or survival, so the demonstrated advantage over an agonist is pharmacological rather than oncological. Patients with severe liver or kidney dysfunction were not studied 1. On cardiovascular risk — where observational data had suggested antagonists might be safer than agonists in men with existing cardiovascular disease — the PRONOUNCE randomised trial was terminated early with fewer events than planned and did not demonstrate a difference, leaving the question open rather than answered 7. Real-world comparisons have reached mixed conclusions 8.

What it is used for

  • Advanced hormone-dependent prostate cancer, as androgen deprivation therapy 12
  • High-risk localised and locally advanced hormone-dependent prostate cancer, before or together with radiotherapy — an indication on the EU authorisation but not the US label 2
  • In practice, the situation where the antagonist is specifically preferred is the patient in whom a testosterone surge would be dangerous: extensive bony metastases, impending spinal cord compression or urinary obstruction, where an agonist would need antiandrogen cover for the first weeks and degarelix does not
  • Degarelix is not used for fertility treatment. The GnRH antagonists used to prevent premature LH surges in assisted reproduction are cetrorelix and ganirelix, which are formulated for short action rather than as a monthly depot

Dosing

Dose
A starting dose of 240 mg, given as two subcutaneous injections of 120 mg at 40 mg/ml, then a maintenance dose of 80 mg at 20 mg/ml every 28 days
Frequency
loading dose once, then once every 28 days; the first maintenance dose is given 28 days after the starting dose
Route
subcutaneous, into the abdomen only, avoiding areas exposed to pressure such as the waistband or near the ribs, with the site varied at each visit
Duration
Continued as long as androgen deprivation is indicated; the extension study reported a median treatment duration of about 43 months, up to 58 months
  • These are the figures from the FDA-approved product information 1. Degarelix is administered by a healthcare professional only 1; it is not a self-administered product, and this entry is reference material rather than advice.
  • There is no antiandrogen cover and no flare protection, because there is no flare to protect against. This is the practical difference from starting an agonist.
  • The concentration is part of the dose, not an afterthought. The label notes that degarelix pharmacokinetics are strongly influenced by the concentration of the injection solution 1, which is why the loading dose is prepared at 40 mg/ml and the maintenance dose at 20 mg/ml, from different reconstitution volumes.
  • A 160 mg monthly maintenance dose at 40 mg/ml was studied in the pivotal trial but is not approved 1.
  • Response is monitored by measuring PSA periodically; if PSA rises, testosterone is measured 1. Because the drug suppresses the pituitary-gonadal axis, diagnostic tests of gonadotropic and gonadal function performed during and after treatment may be affected 1.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Firmagon — androgen deprivation in prostate cancer

approved product information

Source: FIRMAGON (degarelix) FDA prescribing information

Day 0 (starting dose)240 mg, given as two subcutaneous injections of 120 mg each at a concentration of 40 mg/ml
Day 28 and every 28 days thereafter80 mg as a single subcutaneous injection at a concentration of 20 mg/ml

Administered by a healthcare professional, into the abdomen only. Reconstituted product must be given within one hour of adding the diluent. No antiandrogen cover is required, because a GnRH antagonist produces no testosterone surge: in the registration trial 96% of patients were at or below the castrate threshold by day 3, against 0% on leuprolide.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes
Starting dose kit: two single-dose vials each delivering 120 mg, with two prefilled syringes of 3 ml Sterile Water for Injection, two vial adapters and two needles, Maintenance dose kit: one single-dose vial delivering 80 mg, with one prefilled syringe of 4.2 ml Sterile Water for Injection, one vial adapter and one needle
Solvent
Sterile Water for Injection, USP, supplied in a prefilled syringe within the kit
Storage
Store the kit at 20-25 °C, with excursions permitted to 15-30 °C. Reconstituted product must be administered within one hour of adding the Sterile Water for Injection.

Worked example

Not a syringe calculation. Each vial is reconstituted with the diluent syringe supplied with it and the whole dose is given: the 120 mg vial takes 3 ml of Sterile Water and 3 ml is withdrawn to deliver 120 mg at 40 mg/ml; the 80 mg vial takes 4.2 ml and 4 ml is withdrawn to deliver 80 mg at 20 mg/ml. The two concentrations are deliberately different and must not be interchanged, because degarelix pharmacokinetics depend on the concentration injected.

Swirl gently until the solution is clear; do not shake, which causes bubbles. Reconstitution can take up to 15 minutes though it usually takes a few. Reconstitute immediately before administration. The injection is given slowly and deeply into the subcutaneous tissue at a 45-degree angle over about 30 seconds, with aspiration first — if blood appears, the dose is discarded and a new one prepared. This is a professionally administered kit, not a patient-reconstituted vial.

Safety

Side effects

  • Injection site reactions in 35% of patients against under 1% on intramuscular leuprolide: pain (28%), erythema (17%), swelling (6%), induration (4%) and nodule (3%). These were mostly transient, mild to moderate, occurred principally with the starting dose and led to discontinuation in under 1% 1. In the long-term extension, 1% of patients had injection site infections including abscess 1
  • Hot flashes in 26% against 21% on leuprolide 1
  • Increases in transaminases and gamma-glutamyltransferase in 10% against 5% on leuprolide, primarily Grade 1 or 2 and generally reversible; in the 5-year extension, Grade 1 or 2 transaminase elevations occurred in 47% of patients and Grade 3 in 1% 1
  • Weight increase (9%), hypertension (6%), back pain (6%), chills, constipation, arthralgia and urinary tract infection, each around 5% 1
  • Erectile dysfunction, testicular atrophy and gynaecomastia — the expected consequences of androgen deprivation rather than of this drug specifically 1
  • Asthenia, fatigue, fever, night sweats, nausea, dizziness, headache and insomnia in 1-5% of patients 1
  • QT interval prolongation: androgen deprivation therapy of any kind may prolong the QT interval. In the randomised trial, three patients (under 1%) on degarelix and four (2%) on leuprolide had a QTcF of 500 msec or more; the median change from baseline was 12.3 msec on degarelix and 16.7 msec on leuprolide 1
  • Hypersensitivity reactions including anaphylaxis, urticaria and angioedema have been reported after marketing 1
  • The long-term consequences of androgen deprivation — bone loss, loss of muscle mass, metabolic change, mood effects — apply to degarelix as to any agent in this class

Do not use if

  • A history of severe hypersensitivity to degarelix or to any component of the product; patients with such a history should not be re-challenged 1
  • Pregnancy — degarelix can cause fetal harm and loss of pregnancy based on animal data, with embryo-fetal lethality, abortion, increased post-implantation loss and fewer live fetuses at doses below the clinical loading dose on a body surface area basis 1
  • Not indicated in children; safety and effectiveness in paediatric patients have not been established 1
  • Caution in congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and with other QT-prolonging drugs; electrolyte abnormalities should be corrected and periodic ECG and electrolyte monitoring considered 1
  • Patients with severe liver or kidney dysfunction have not been studied, so caution is warranted 1
  • Degarelix may impair fertility in males and females of reproductive potential 1

Interactions

Degarelix is not a substrate, inducer or inhibitor of the CYP450 enzymes or of P-glycoprotein in vitro, and no quantitatively significant metabolites are detectable in plasma after subcutaneous administration, so pharmacokinetic interactions are not expected 1. The interaction that matters clinically is additive QT prolongation: androgen deprivation therapy may prolong the QT interval, and the label advises weighing the benefit against the risk in patients with congenital long QT syndrome, congestive heart failure or frequent electrolyte abnormalities, and in those taking other drugs known to prolong the QT interval 1. Because degarelix suppresses the pituitary-gonadal axis, diagnostic tests of pituitary gonadotropic and gonadal function carried out during and after treatment may be affected 1.

Sources