Degarelix

Summary

Degarelix (Firmagon) is a synthetic GnRH receptor antagonist approved for the treatment of advanced prostate cancer. Unlike GnRH agonists, it causes immediate androgen deprivation without an initial testosterone flare, making it advantageous in patients with symptomatic or high-burden disease.

Mechanism of Action

Competitively and reversibly binds to pituitary GnRH receptors, immediately suppressing LH and FSH secretion, leading to rapid reduction of testosterone to castrate levels without an initial testosterone surge (flare).

Routes of Administration

Goals & Uses

• Cardiovascular risk reduction vs GnRH agonistsCardiologyModerate
• Prevention of testosterone flareOncology / Hormonal SafetyHigh
• Advanced prostate cancer treatmentOncologyHigh
• Neoadjuvant/adjuvant to radiotherapyOncologyModerate
• Androgen deprivation therapy (ADT)EndocrinologyHigh

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• Women and pediatric patientsPopulationHigh
• Hypersensitivity to degarelix or excipientsAllergyHigh

Adverse Effects

• Elevated liver enzymes (AST/ALT)HepatotoxicityUncommon
• Decreased bone mineral densityMusculoskeletalCommon
• Hot flashesEndocrine / VasomotorCommon
• QT/QTc prolongationCardiovascularUncommon
• Weight gainMetabolicCommonIncrease in body weight
• Injection site reactions (pain, erythema, swelling)LocalCommon

Drug Interactions

• Class III antiarrhythmics (amiodarone, sotalol)High
• QT-prolonging agents (e.g., antiarrhythmics, antipsychotics)High
• Class IA antiarrhythmics (quinidine, procainamide)High

Population Constraints

• Patients with congenital long QT syndromeCardiovascularRelative
• Patients with severe hepatic impairmentHepaticRelative
• Elderly patients (≥65 years)Age RelatedRelative
• Patients with severe renal impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionApprovedApproved: Advanced hormone-dependent prostate cancerEMA approved 2009 as Firmagon; full marketing authorization.
• United StatesApprovedApproved: Advanced prostate cancerFDA approved December 2008 under brand name Firmagon; 240 mg loading dose followed by 80 mg monthly maintenance.
• United KingdomApprovedApproved: Advanced hormone-dependent prostate cancerMHRA approved; retains approval post-Brexit under existing marketing authorization.

Approved by the FDA in December 2008 and by the EMA for treatment of advanced hormone-dependent prostate cancer. Administered as a monthly subcutaneous depot injection.

Evidence & Sources

No sources recorded yet.