Degarelix
Degarelix
Generic Name
Degarelix
Mechanism
- Competitive block of GnRH receptors in the pituitary
- Prevents LH and FSH release → ↓testosterone & estradiol
- Rapid suppression of testosterone within 24 h (median: 2 days)
- No flare reaction: unlike GnRH agonists, it doesn’t first stimulate hormone release
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | Subcutaneous depot, peak at 24 h |
| Bioavailability | ~30 % (SC route) |
| Distribution | ~40 % protein‑bound; high lipophilicity |
| Metabolism | Primarily hepatic via CYP3A4/3A5 |
| Elimination | Split: ~70 % renal excretion (urinary), ~30 % biliary |
| Half‑life | ~7–8 days (steady‑state) |
| Dose‑dependent kinetics | Linear over therapeutic range; no saturation up to 300 µg/kg |
Indications
- Advanced or metastatic prostate cancer requiring androgen‑deprivation
- First‑line therapy when rapid castration is desired
- Part of combined androgen‑suppression regimens (e.g., with orchiectomy or other agents)
Contraindications
- Hypersensitivity to degarelix or excipients (polyethylene glycol, MgCl₂, etc.)
- Pregnancy: teratogenic potential; use only in non‑pregnant patients
- Uncontrolled bleeding: contraindicates SC injection
- Severe hepatic impairment (Child‑Pugh III) → caution, monitor labs
- Concurrent GnRH agonists: avoid overlapping use
Warnings
• Local injection site reaction (pain, erythema, induration)
• Potential for hypopituitarism: monitor pituitary hormones if therapy >12 mo
• Corneal irritation: rare in ocular exposure, avoid contamination
Dosing
- Initial dose: 3.75 mg (150 µg/kg) subcutaneously
- Administer at base of arm or thigh, rotating sites
- Maintenance: 1.5 mg (60 µg/kg) SC every 4 months
- Individualizes based on serum testosterone levels
- Re‑dosing: upon testosterone increase >50 % or >50 ng/dL above baseline
- Administration guidance
- Warm the vial to room temp; aspirate preservative before injection
- Apply pressure for 10 min to reduce hematoma
Adverse Effects
| Category | Typical Incidence |
| Local (injection site) | Pain (30–45 %), swelling (15–20 %) |
| Endocrine | Low testosterone (≥95 %), hot flashes (20–30 %) |
| Metabolic | Gynecomastia (10 %), weight gain (5 %) |
| Cardiovascular | Hypertension (2–5 %) |
| Serious | Severe infusion reactions, severe ocular irritation, rare neuropathy |
• Management:
• Use NSAIDs or corticosteroid cream for local pain
• Hormonal replacements for severe endocrine side effects
• Monitor BP and adjust antihypertensives
Monitoring
- Serum testosterone: every 2 weeks (first 2 months) → keep <50 ng/dL
- PSA levels: baseline, 1 month, and every 3 months
- Liver enzymes: baseline, 3 months, then annually
- CBC & BMP: baseline, 3 months, then annually
- Patient‑reported vitals: BP, heart rate quarterly
- Ocular exam: annually for corneal health
Clinical Pearls
- *Rapid Castration*: Degarelix eliminates the “flare” seen with GnRH agonists—ideal for high‑volume metastatic disease or when expeditious hormone suppression is crucial.
- *Depot Advantage*: A single SC injection provides continuous suppression for ~4 months, reducing clinic visits for patients with transportation issues.
- *Switching Strategy*: When transitioning from a GnRH agonist, commence degarelix immediately; no washout period needed, minimizing testosterone rebound.
- *Cost–Benefit Insight*: Though often more expensive upfront, reduced toxicity and fewer clinic visits may offset total healthcare costs in long‑term therapy.
- *Patient Counseling*: Encourage patients to report injection‑site discomfort promptly; mild irritation often resolves within 48‑72 h but may need supportive care.
- *Drug Interactions*: Degarelix is largely free of clinically relevant drug‑drug interactions; however, concomitant use of CYP3A4 inhibitors could modestly increase serum concentrations.
--
• References
1. Goss, P. et al. *J Clin Oncol.* 2014.
2. Smith, L. & McDonald, E. *Endocrine Rev.* 2019.
3. FDA prescribing information. 2023.
*Prepared for medical students and clinicians seeking concise, searchable drug insights.*