Firmagon - Drug Monograph

Introduction

Firmagon (degarelix) is a gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the FDA in 2008 for the treatment of advanced prostate cancer. Unlike traditional GnRH agonists, Firmagon provides immediate suppression of testosterone without the initial surge that can cause disease flare.

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 testicles without the initial testosterone surge associated with GnRH agonists.

Indications

• Advanced hormone-sensitive prostate cancer
• Palliative treatment of advanced prostate cancer

Dosage and Administration

Pharmacokinetics

Contraindications

• Known hypersensitivity to degarelix or any component of the formulation
• Women who are or may become pregnant
• Pediatric patients

Warnings and Precautions

• QT prolongation: May prolong QT interval; monitor patients with congenital long QT syndrome, electrolyte abnormalities, or taking other QT-prolonging drugs
• Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment
• Injection site reactions: Common (40% of patients); may include pain, erythema, swelling, or induration
• Hypersensitivity reactions: Including anaphylaxis reported

Drug Interactions

• Class IA/III antiarrhythmics: Increased risk of QT prolongation
• Other QT-prolonging drugs: Additive effects on QT interval
• Drugs metabolized by CYP450: Unlikely to cause significant interactions due to minimal CYP450 metabolism

Adverse Effects

• Injection site reactions (pain, erythema, swelling)
• Hot flashes
• Increased weight
• Increased transaminases

• Fatigue
• Constipation
• Hypertension
• Back pain
• Chills
• Urinary tract infections

• QT prolongation
• Anaphylaxis
• Cardiovascular events

Monitoring Parameters

• Testosterone levels (target: <50 ng/dL)
• PSA levels at regular intervals
• Liver function tests at baseline and periodically
• Electrolytes (particularly potassium and magnesium)
• ECG for QT prolongation in at-risk patients
• Injection sites for reactions
• Bone density in long-term therapy

Patient Education

• Expect immediate testosterone suppression without disease flare
• Report any injection site reactions that are severe or persistent
• Be aware of potential hot flashes and discuss management strategies
• Understand the importance of regular monitoring appointments
• Report symptoms of allergic reactions (rash, itching, swelling)
• Inform all healthcare providers about Firmagon therapy
• Notify physician of any cardiac symptoms (palpitations, dizziness)
• Understand that Firmagon is not a cure but helps control disease progression

References

1. FDA Prescribing Information: Firmagon (degarelix). 2022 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. 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 4. Shore ND, et al. New considerations for ADT in advanced prostate cancer and the emerging role of GnRH antagonists. Prostate Cancer and Prostatic Diseases. 2013;16(1):7-15 5. National Comprehensive Cancer Network (NCCN) Guidelines: Prostate Cancer. Version 4.2023