Introduction
Degarelix is a gonadotropin-releasing hormone (GnRH) receptor antagonist used in the treatment of advanced prostate cancer. Unlike traditional GnRH agonists, degarelix provides immediate suppression of testosterone without the initial testosterone surge that can exacerbate disease symptoms. It was approved by the FDA in 2008 and represents an important therapeutic option for patients requiring rapid androgen deprivation therapy.
Mechanism of Action
Degarelix competitively binds to pituitary GnRH receptors, resulting in immediate suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. This leads to rapid reduction of testosterone production from the testes without the initial surge associated with GnRH agonists. Within three days of administration, testosterone levels typically decrease to castrate levels (<50 ng/dL).
Indications
- Advanced hormone-sensitive prostate cancer
- Management of patients requiring rapid testosterone reduction to prevent potential clinical complications
- Patients in whom other hormonal therapies are not appropriate or have failed
Dosage and Administration
Initial dose: 240 mg administered as two subcutaneous injections of 120 mg each Maintenance dose: 80 mg subcutaneously every 28 days Administration:- Administer as subcutaneous injections in the abdominal area
- Rotate injection sites
- Reconstitute with sterile water for injection
- Use within 1 hour after reconstitution
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution in severe impairment
- Elderly: No dosage adjustment required
Pharmacokinetics
Absorption: Bioavailability approximately 30-40% following subcutaneous administration Distribution: Volume of distribution approximately 1 L/kg; 90% protein-bound Metabolism: Undergoes peptide hydrolysis with no specific cytochrome P450 involvement Elimination: Terminal half-life approximately 43-53 days; primarily excreted in feces (70-80%) with minimal renal excretionContraindications
- Known hypersensitivity to degarelix or any component of the formulation
- Women who are or may become pregnant
- Pediatric patients
Warnings and Precautions
QT Prolongation: Androgen deprivation therapy may prolong QT interval; consider periodic ECG monitoring Hepatic Impairment: Use with caution in patients with moderate to severe hepatic impairment Injection Site Reactions: Common, including pain, erythema, swelling, and induration Bone Loss: Increased risk of osteoporosis and fractures with long-term therapy Metabolic Effects: May cause hyperglycemia and increased risk of diabetes mellitus Cardiovascular Risk: Increased incidence of myocardial infarction, sudden cardiac death, and strokeDrug Interactions
- Other QT-prolonging drugs: Additive risk of QT prolongation (antiarrhythmics, antipsychotics, antibiotics)
- No known clinically significant pharmacokinetic interactions with CYP450 substrates
- Limited data on interactions with other hormonal therapies
Adverse Effects
Common (≥10%):- Injection site reactions (pain, erythema, swelling)
- Hot flashes (26%)
- Increased weight (10%)
- Fatigue (7%)
- Increased transaminases (5-8%)
- QT interval prolongation
- Cardiovascular events
- Severe allergic reactions
- Hepatic transaminase elevations
Monitoring Parameters
- Testosterone levels at baseline and periodically during therapy
- Prostate-specific antigen (PSA) levels every 3 months
- Liver function tests at baseline and periodically
- Bone mineral density baseline and annually
- ECG monitoring in patients at risk for QT prolongation
- Fasting glucose and lipid profile
- Signs and symptoms of cardiovascular disease
Patient Education
- Explain the expected therapeutic effects and potential side effects
- Instruct on proper injection site rotation and recognition of injection site reactions
- Discuss management strategies for hot flashes
- Emphasize importance of regular follow-up appointments and monitoring
- Counsel on bone health maintenance, including calcium and vitamin D supplementation
- Discuss lifestyle modifications for cardiovascular risk reduction
- Inform about potential impact on sexual function
- Advise to report any chest pain, palpitations, or unusual symptoms promptly
References
1. FDA Prescribing Information: Degarelix (2019) 2. Klotz L, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU International. 2008;102(11):1531-1538. 3. Shore ND, et al. New developments in castration-resistant prostate cancer: focus on novel non-hormonal agents. European Urology. 2011;59(2):202-210. 4. Van Poppel H, et al. Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 3 dosage-finding study in the treatment of prostate cancer. European Urology. 2008;54(4):805-813. 5. National Comprehensive Cancer Network (NCCN) Guidelines: Prostate Cancer (2023) 6. Albertsen PC, et al. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. The Prostate. 2014;74(15):1484-1493.