Degarelix (Firmagon)
Degarelix Acetate (N-acetyl-D-Nal(2)-D-Cpa-D-Pal(3)-Ser-Aph(Hor)-D-Aph(Cbm)-Leu-ILys-Pro-D-Ala-NH2)
FDA-approved (NDA022201, 2008) synthetic decapeptide GnRH antagonist for advanced prostate cancer that achieves castrate testosterone levels within 1-3 days without testosterone flare (PMID 19035858).
Last updated: 2026-03-10
Safety Summary
In the CS21 Phase III trial (n=207 degarelix, n=201 leuprolide), the overall adverse event rate was 79% for degarelix vs 78% for leuprolide (PMID 19035858). Injection site reactions occurred in 35% of degarelix patients vs <1% leuprolide (pain 28%, erythema 17%, swelling 6%, induration 4%, nodule 3%), mostly transient and mild-to-moderate. Hot flashes: 26% degarelix vs 21% leuprolide. Liver enzyme elevations: 10% vs 5%, mostly Grade 1-2 and reversible. In the extension study (median 43 months, n=385), injection site infections including abscess occurred in 1% of patients (FDA Label). Anti-degarelix antibody development was observed in 10% of patients at 1 year but did not affect efficacy or safety (FDA Label). The 2025 meta-analysis (PMID 41216753) confirmed higher overall AE rate with degarelix (RR 1.07, p<0.001) but no increase in severe complications (RR 0.89, p=0.43) or death (RR 0.64, p=0.16). A 2026 FAERS analysis identified 53 previously unlabeled AE signals including interstitial lung disease, cardiac failure, osteoporotic fracture, and hyperkalemia (PMID 41776145).
Known Side Effects
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Who Should NOT Use This
Anaphylaxis, urticaria, and angioedema reported post-marketing. Patients with prior severe hypersensitivity should not be re-challenged (FDA Label Section 4, 5.1).
Embryo-fetal toxicity demonstrated in animal studies at doses less than clinical loading dose. Caused embryo-fetal lethality and abortion in rabbits and rats (FDA Label Section 5.4, 8.1).
Safety and effectiveness not established in pediatric patients (FDA Label Section 8.4).
ADT may prolong QT interval. In CS21 trial, 3 degarelix patients (<1%) and 4 leuprolide patients (2%) had QTcF >=500 msec. Median QTcF change: degarelix 12.3 msec, leuprolide 16.7 msec (FDA Label Section 5.2).
Not studied in severe hepatic dysfunction (Child-Pugh C). Mild/moderate impairment: degarelix exposure decreased by 10-18%, no dose adjustment needed but monthly testosterone monitoring recommended (FDA Label Section 8.7).
Limited data in moderate/severe renal impairment. 20-30% of dose renally excreted. Use with caution (FDA Label Section 8.6).
ADT associated with cardiovascular risk. PRONOUNCE trial (n=545) found no significant difference in MACE between degarelix and leuprolide (HR 1.28, p=0.53) but was underpowered (PMID 34459214). Cochrane review noted CV event data very uncertain (PMID 34350976).
Talk to Your Doctor
Before considering Degarelix (Firmagon), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-20]
Evidence Assessment
Tier 1 -- FDA-approved as a New Molecular Entity in December 2008 (NDA022201). Pivotal Phase III CS21 trial (NCT00295750, n=610) demonstrated non-inferiority to leuprolide for testosterone suppression over 12 months (PMID 19035858). Five-year extension data confirmed long-term efficacy and safety (PMID 24661333). Additional Phase III trials in Japan for 3-month formulation (PMID 29624800, n=234). PRONOUNCE cardiovascular outcomes trial (NCT02663908, n=545) (PMID 34459214). Multiple Phase IIIb studies (NCT00831233) and Phase II studies. Three systematic reviews and meta-analyses (PMID 27390687, PMID 34350976, PMID 41216753). Well-characterized safety profile from clinical trials and post-marketing surveillance including FAERS analysis of 2,984 reports (PMID 41776145). Also approved in EU (EMA) and Japan (Gonax). Superiority over GnRH agonists for survival or cardiovascular outcomes remains less certain because comparative follow-up is limited and PRONOUNCE was underpowered after early termination (PMID 34350976, PMID 34459214).
1The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancerNCT00295750PMID 19035858
Klotz L et al. - BJU International (2008) - RCT (Phase III) - 610 (207 degarelix 240/80 mg, 202 degarelix 240/160 mg, 201 leuprolide)
Degarelix non-inferior to leuprolide for testosterone suppression: 97.2% (degarelix 240/80), 98.3% (240/160), 96.4% (leuprolide) achieved castrate levels from Day 28-364. 96.1% of degarelix patients achieved castrate testosterone by Day 3 vs 0% leuprolide. PSA levels significantly lower at Day 14 and 28 (p<0.001). Injection site reactions 40% degarelix vs <1% leuprolide (p<0.001). UTI lower with degarelix (3% vs 9%, p<0.01).
Limitations: Open-label design. Leuprolide arm did not receive anti-androgen flare protection. Manufacturer-funded (Ferring).
2Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelixNCT00451958PMID 24661333
Crawford ED et al. - Urology (2014) - Phase III extension (crossover) - 385 (125+126 continued degarelix, 69+65 crossed from leuprolide)
Degarelix well tolerated over 5 years. PSA-PFS hazard rate significantly decreased after crossover from leuprolide to degarelix (0.20 to 0.09, p=0.002). In patients with baseline PSA >20 ng/mL, crossover benefit also significant (0.38 to 0.19, p=0.019). No new safety concerns.
Limitations: Extension study, not independently randomized for 5-year comparison. Open-label. Manufacturer-funded (Ferring).
3A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancerNCT00451958PMID 21788033
Crawford ED et al. - The Journal of Urology (2011) - Phase III extension - 385 (median 27.5-month follow-up)
PSA-PFS hazard rate decreased significantly after switch from leuprolide to degarelix. Testosterone and PSA suppression maintained in patients continuing degarelix. AE frequency decreased with time.
Limitations: Extension study design. Open-label. Manufacturer-funded (Ferring). Crossover analysis is post-hoc.
4Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized TrialNCT02663908PMID 34459214
Lopes RD et al. - Circulation (2021) - RCT (Phase III, prospective CV outcomes) - 545 (of planned 900; terminated early)
First prospective CV outcomes trial comparing GnRH antagonist vs agonist. MACE in 15 (5.5%) degarelix vs 11 (4.1%) leuprolide patients (HR 1.28, 95% CI 0.59-2.79, p=0.53). No significant difference. Study terminated early due to slow enrollment and fewer-than-projected events.
Limitations: Terminated early, severely underpowered (545 of 900 planned). COVID-19 impact on enrollment. Open-label. Cannot draw definitive conclusions about CV safety. Manufacturer-funded (Ferring).
5Degarelix for treating advanced hormone-sensitive prostate cancer (Cochrane Review)PMID 34350976
Zengerling F et al. - Cochrane Database of Systematic Reviews (2021) - Systematic review and meta-analysis - 11 studies, up to 2,887 participants
No data available for overall survival or cancer-specific survival. Serious AEs may be similar (RR 0.80, 95% CI 0.62-1.05; low certainty). QoL similar (moderate certainty). CV event data very uncertain (RR 0.15, 95% CI 0.04-0.61; very low certainty, from single small high-risk study). Injection site pain increased (RR 15.68, 95% CI 7.41-33.17; moderate certainty). Maximum follow-up only 14 months.
Limitations: No OS or CSS data. Short follow-up. Low to very low certainty for several outcomes. CV finding from single underpowered study in high-risk population.
6Effectiveness and safety of degarelix compared to GnRH agonists for prostate cancer: a systematic review and meta-analysisPMID 41216753
Chai Y et al. - The Aging Male (2025) - Systematic review and meta-analysis - Multiple RCTs pooled
Higher overall AE rate (RR 1.07, p<0.001) but no increase in severe complications (RR 0.89, p=0.43) or death (RR 0.64, p=0.16). Lower CV events (RR 0.7, p=0.03), lower musculoskeletal events (RR 0.79, p=0.01), lower urinary AEs (RR 0.46, p<0.00001). Higher injection site reactions (RR 19.17, p<0.00001). 96.5% castration at Day 3 vs 0% for agonists (RR 356.05). More sustained testosterone suppression at 12 months (96.1% vs 74.3%, RR 1.3, p=0.03).
Limitations: Heterogeneity across included studies. CV benefit driven by earlier post-hoc analyses. Not independent of manufacturer-sponsored data.
7Degarelix for the treatment of advanced prostate cancer compared with GnRh-Agonists: a systematic review and meta-analysisPMID 27390687
Hosseini SA et al. - Medical Journal of the Islamic Republic of Iran (2016) - Systematic review and meta-analysis - 6 RCTs, 2,296 patients
Only significant safety difference was injection site complications (OR 46.34, p<0.001). General mortality lower in degarelix group (OR 2.06, p=0.03) but drug-related mortality not different. IPSS reduction greater with degarelix at week 12 (MD -1.85, p=0.001). Testosterone reduction faster in first 28 days (OR 11.58, p<0.001). No difference after Day 28.
Limitations: Small number of included studies. Follow-up limited to 3-12 months. Some heterogeneity.
8Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: A phase III studyNCT01964170PMID 29624800
Ozono S et al. - Cancer Science (2018) - RCT (Phase III) - 234 (117 degarelix, 117 goserelin)
3-month degarelix formulation (480 mg q84d maintenance) non-inferior to goserelin for castration rate. Cumulative castration rate 95.1% degarelix vs 100.0% goserelin. Faster decreases in testosterone, LH, FSH, and PSA with degarelix. Most common AEs were injection site reactions.
Limitations: Open-label. Japanese population only. Castration rate numerically lower for degarelix though non-inferior. Manufacturer-funded (Ferring).
9A Phase II, Randomized, Open-Label Study of Neoadjuvant Degarelix versus LHRH Agonist in Prostate Cancer Patients Prior to Radical ProstatectomyPMID 27756786
Sayyid RK et al. - Clinical Cancer Research (2017) - RCT (Phase II) - 39 (3 arms: degarelix, degarelix + bicalutamide, LHRH agonist + bicalutamide)
Intratumoral DHT levels higher in degarelix-only arm vs combination arms (0.87 vs 0.26 and 0.23 ng/g, p<0.01). Serum FSH significantly lower in degarelix arms vs LHRH agonist arm (0.55-0.65 vs 3.65, p<0.01).
Limitations: Small sample size (n=39). Not powered for clinical outcomes. Open-label.
10Degarelix versus goserelin (+ antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: results from a phase IIIb studyNCT00831233PMID 23258223
Anderson J et al. - Urologia Internationalis (2013) - RCT (Phase IIIb) - 40 (27 degarelix, 13 goserelin + bicalutamide)
Degarelix non-inferior to goserelin + bicalutamide for IPSS reduction at week 12 (p=0.20 full analysis; p=0.04 per-protocol). 85% vs 46% reported improved QoL (p=0.01). Prostate volume reduction 42% vs 25% (p=0.04, post hoc). Stopped early due to recruitment difficulties.
Limitations: Very small sample size (n=40). Stopped early. Post-hoc prostate volume analysis. Manufacturer-funded (Ferring).
11Degarelix as an intermittent androgen deprivation therapy for one or more treatment cycles in patients with prostate cancerNCT00801242PMID 24954791
Boccon-Gibod L et al. - European Urology (2014) - Phase II (open-label, uncontrolled) - 213 (191 entered first off-treatment period)
Median time to PSA >4 ng/mL was 392 days (first off-treatment). Testosterone recovered to >0.5 ng/mL at median 112 days and >2.2 ng/mL at 168 days. Sexual function improved during off-treatment.
Limitations: No comparator arm. Open-label. Small number completed multiple cycles. Manufacturer-funded (Ferring).
12A Phase II trial of 8 weeks of degarelix for prostate volume reduction: Efficacy and hormonal recoveryNCT01446991PMID 29398594
Korzeniowski MA et al. - Brachytherapy (2018) - Phase II (open-label) - 50
Median prostate volume reduced from 65.0 cc to 48.2 cc at 8 weeks (26.2% decrease). Testosterone recovered to age-adjusted normal at median 34.1 weeks. FSH and LH remained elevated beyond 12 months despite testosterone recovery.
Limitations: No comparator arm. Small sample. Single-center.
13A Proof-of-Concept Clinical Trial of A Single Luteal Use of Long-Acting Gonadotropin-Releasing Hormone Antagonist Degarelix in Controlled Ovarian Stimulation for In Vitro FertilizationNCT03240159PMID 29545772
Papanikolaou EG et al. - Frontiers in Endocrinology (2018) - Proof-of-concept (Phase II) - 10 (5 donors + 5 infertile women)
Single luteal dose of 0.5 mL degarelix effectively downregulated pituitary for up to 22 days. All patients achieved LH suppression. 3 of 5 infertile patients achieved pregnancy.
Limitations: Extremely small sample (n=10). Proof-of-concept only. No comparator. Retrospectively registered.
14Disproportionality analysis of adverse events associated with degarelix: a real-world study from the FDA Adverse Event Reporting System (FAERS) databasePMID 41776145
Lin X et al. - Clinical & Translational Oncology (2026) - Pharmacovigilance (disproportionality analysis) - 2,984 degarelix reports from 17,048,812 total FAERS reports (2014-2024)
130 Preferred Terms showed significant disproportionate reporting across 22 System Organ Classes. 53 AEs not on label identified including interstitial lung disease, cardiac failure, osteoporotic fracture, hyperkalemia.
Limitations: FAERS data are voluntary reports with inherent reporting bias. Cannot establish causality. No denominator for rate calculation.
15Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancerPMID 20110043
Steinberg M - Clinical Therapeutics (2009) - Review - N/A (review of Phase II and III data)
Comprehensive review at time of approval. Phase II (n=187): 240 mg loading dose achieved 92% castration by Day 3. Phase III (n=610): non-inferior to leuprolide. Forms gel depot upon SC injection.
Limitations: Review article. Limited to data available shortly after approval.
16Androgen deprivation, androgen receptor-targeted vaccination, and nivolumab in patients with high-risk localized prostate cancerNCT04989946PMID 41781018
Jarrard D et al. - Journal for Immunotherapy of Cancer (2026) - RCT (Phase II, 3-arm, first stage) - 24 (6 degarelix alone, 9 pTVG-AR + degarelix, 9 pTVG-AR + degarelix + nivolumab)
AR-targeted vaccine (pTVG-AR) given before degarelix showed improved 1-year PSA-PFS (89% Arm 2 vs 33% Arm 1, p=0.039). Adding nivolumab did not improve outcomes.
Limitations: Very small sample (n=24). First stage of pilot study. Not powered for definitive conclusions.
17A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate CancerNCT04666129PMID 37060432
De La Cerda J et al. - Targeted Oncology (2023) - Phase I (open-label) - 25 (15 Part 1, 10 Part 2)
Patients transitioned from degarelix or leuprolide to relugolix + abiraterone or apalutamide. Castration levels of testosterone maintained. Safety profile consistent with individual medications.
Limitations: Small Phase I. Open-label. Manufacturer-funded.
18Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trialNCT03080116PMID 29606109
Tosco L et al. - BMC Cancer (2018) - RCT protocol (Phase II, double-blind, placebo-controlled) - 84 planned (42 per arm)
Protocol for evaluating apalutamide + degarelix vs placebo + degarelix as neoadjuvant therapy before prostatectomy. Primary endpoint: minimal residual disease.
Limitations: Protocol paper; results not yet published at time of review.
19Factors Predicting the Off-treatment Duration in Patients with Prostate Cancer Receiving Degarelix as Intermittent Androgen Deprivation TherapyNCT00801242PMID 28753747
Abrahamsson PA et al. - European Urology Focus (2017) - Multivariable analysis of Phase II data - 191
Baseline PSA (p<0.0001) and age (p=0.004) predicted off-treatment duration. Patients with baseline PSA <=4 ng/mL had longest off-treatment period.
Limitations: Post-hoc analysis. No comparator arm. Manufacturer-funded (Ferring).
20Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study DesignNCT02663908PMID 34396210
Melloni C et al. - JACC CardioOncology (2020) - Trial design paper - 364 enrolled at time of publication (of planned 900)
Design of first prospective CV outcomes trial in ADT. Mean age 74 years, 80% hypertension/dyslipidemia, 40% prior MI, 65% prior revascularization.
Limitations: Design paper only. Trial subsequently terminated early.