May 25, 2017
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"A study on ejaculation and prostate cancer risk, which made a big splash at last year's annual meeting of the American Urological Association (AUA), was published online March 29 in European Urology.

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Mechanism Of Action

Degarelix is a GnRH receptor antagonist. It binds reversibly to the pituitary GnRH receptors, thereby reducing the release of gonadotropins and consequently testosterone.


A single dose of 240 mg FIRMAGON causes a decrease in the plasma concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and subsequently testosterone.

FIRMAGON is effective in achieving and maintaining testosterone suppression below the castration level of 50 ng/dL.

Figure 1: Plasma Testosterone Levels from Day 0 to 364 for Degarelix 240 mg/80 mg (Median with Interquartile Ranges)

Plasma Testosterone Levels from Day 0 to 364 - Illustration



FIRMAGON forms a depot upon subcutaneous administration, from which degarelix is released to the circulation. Following administration of FIRMAGON 240 mg at a product concentration of 40 mg/mL, the mean Cmax was 26.2 ng/mL (coefficient of variation, CV 83%) and the mean AUC was 1054 ng·day/mL (CV 35%). Typically Cmax occurred within 2 days after subcutaneous administration. In prostate cancer patients at a product concentration of 40 mg/mL, the pharmacokinetics of degarelix were linear over a dose range of 120 to 240 mg. The pharmacokinetic behavior of the drug is strongly influenced by its concentration in the injection solution.


The distribution volume of degarelix after intravenous ( > 1 L/kg) or subcutaneous administration ( > 1000L) indicates that degarelix is distributed throughout total body water. In vitro plasma protein binding of degarelix is estimated to be approximately 90%.


Degarelix is subject to peptide hydrolysis during the passage of the hepato-biliary system and is mainly excreted as peptide fragments in the feces. No quantitatively significant metabolites were detected in plasma samples after subcutaneous administration. In vitro studies have shown that degarelix is not a substrate, inducer or inhibitor of the CYP450 or p-glycoprotein transporter systems.


Following subcutaneous administration of 240 mg FIRMAGON at a concentration of 40 mg/mL to prostate cancer patients, degarelix is eliminated in a biphasic fashion, with a median terminal half-life of approximately 53 days. The long half-life after subcutaneous administration is a consequence of a very slow release of degarelix from the FIRMAGON depot formed at the injection site(s). Approximately 20-30% of a given dose of degarelix was renally excreted, suggesting that approximately 70-80% is excreted via the hepato-biliary system in humans. Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9L/hr.

Effect of Age, Weight and Race

There was no effect of age, weight or race on the degarelix pharmacokinetic parameters or testosterone concentration.

Clinical Studies

The safety and efficacy of FIRMAGON were evaluated in an open-label, multi-center, randomized, parallel-group study in patients with prostate cancer A total of 620 patients were randomized to receive one of two FIRMAGON dosing regimens or leuprolide for one year:

  1. FIRMAGON at a starting dose of 240 mg (40 mg/mL) followed by monthly doses of 160 mg (40 mg/mL) subcutaneously,
  2. FIRMAGON at a starting dose of 240 mg (40 mg/mL) followed by monthly doses of 80 mg (20 mg/mL) subcutaneously,
  3. leuprolide 7.5 mg intramuscularly monthly.

Serum levels of testosterone were measured at screening, on Day 0, 1, 3, 7, 14, and 28 in the first month, and then monthly until the end of the study.

The clinical trial population (n=610) across all treatment arms had an overall median age of approximately 73 (range 50 to 98). The ethnic/racial distribution was 84% white, 6% black and 10% others. Disease stage was distributed approximately as follows: 20% metastatic, 29% locally advanced (T3/T4 Nx M0 or N1 M0), 31% localized (T1 or T2 N0 M0) and 20% classified as other (including patients whose disease metastatic status could not be determined definitively - or patients with PSA relapse after primary curative therapy). In addition, the median testosterone baseline value across treatment arms was approximately 400 ng/dL.

The primary objective was to demonstrate that FIRMAGON is effective with respect to achieving and maintaining testosterone suppression to castration levels (T ≤ 50 ng/dL), during 12 months treatment. The results are shown in Table 2.

Table 2: Medical Castration Rates (Testosterone ≤ 50 ng/dL) from Day 28 to Day 364

  FIRMAGON 240/160 mg
FIRMAGON 240/80 mg
Leuprolide 7.5 mg
No. of Responders 199 202 194
Castration Rate (95% CIs)* 98.3%
(94.8; 99.4)
(93.5; 98.8)
(92.5; 98.2)
* Kaplan Meier estimates within group

Percentage changes in testosterone from baseline to Day 28 (median with interquartile ranges) are shown in Figure 2 and the percentages of patients who attained the medical castration of testosterone ≤ 50 ng/dL are summarized in Table 3.

Figure 2: Percentage Change in Testosterone from Baseline by Treatment Group until Day 28 (Median with Interquartile Ranges)

Percentage Change in Testosterone from Baseline - Illustration

Table 3: Percentage of Patients Attaining Testosterone ≤ 50 ng/dL within the First 28 Days

  FIRMAGON 240/160 mg
FIRMAGON 240/80 mg
Leuprolide 7.5
mg N=201
Day 1 44% 52% 0%
Day 3 96% 96% 0%
Day 7 99% 99% 1%
Day 14 99% 99% 18%
Day 28 99% 100% 100%

In the clinical trial, PSA levels were monitored as a secondary endpoint. PSA levels were lowered by 64% two weeks after administration of FIRMAGON, 85% after one month, 95% after three months, and remained suppressed throughout the one year of treatment. These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline is related to a clinical benefit.

Last reviewed on RxList: 1/25/2016
This monograph has been modified to include the generic and brand name in many instances.

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