Degaris

Approved Indications:

• Advanced Prostate Cancer (Hormone‑Sensitive, Non‑Metastatic or Metastatic):
• For rapid reduction of testosterone levels in adult men with advanced prostate cancer.
• Androgen Deprivation Therapy (ADT):
• As first-line medical castration when rapid testosterone suppression is needed (e.g., symptomatic disease or impending spinal cord compression).

Clinically Accepted Off-label Uses:

• Intermittent ADT protocols.
• Use in combination with androgen receptor-targeted therapies or chemotherapy in metastatic hormone-sensitive prostate cancer (off-label/under investigation).

Adults:

• Loading Dose:
• 240 mg subcutaneous injection (2 × 120 mg cartridges) in the abdominal region.
• Maintenance Dose:
• 80 mg subcutaneously every 28 days, starting 28 days after initial dose.
• Administration Note:
• Administer in lower abdominal wall; rotate injection sites.

Special Populations:

• Elderly:
• No dose adjustment required.
• Renal Impairment:
• No adjustment needed for mild to moderate renal dysfunction; insufficient data in severe impairment.
• Hepatic Impairment:
• Use with caution in moderate to severe hepatic impairment; no formal dose change established.
• Pediatrics:
• Not indicated; safety and effectiveness not established in children.

Degarelix acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It binds directly and competitively to pituitary GnRH receptors, immediately suppressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release without the flare associated with GnRH agonists. By rapidly decreasing LH and FSH, it leads to rapid suppression of testosterone production from the testes, reducing stimulation of prostate cancer cells and achieving chemical castration.

Absorption:

• Subcutaneous administration leads to moderate absorption; serum levels peak at ~2 hours post-injection.

Distribution:

• Volume of distribution: ~2 L/kg.

Metabolism:

• Metabolized by liver peptidases and nonspecific proteases; not via CYP450 enzymes.

Elimination:

• Excreted primarily via urine and faeces; half-life varies with dose and accumulation (~53 days after repeated administration).

Onset of Action:

• Testosterone suppression to castrate levels (≤ 0.5 ng/mL) occurs within 3 days.

• Pregnancy:
• Not applicable; degarelix is indicated only in males.
• Lactation:
• Not relevant; degarelix use in women or nursing mothers is not indicated.

• Primary Class: Hormonal therapy
• Subclass: GnRH receptor antagonist

• Known hypersensitivity to degarelix acetate or any component (e.g., poloxamer, mannitol).
• Women of reproductive potential (no indication).
• Severe hepatic impairment (use with caution).

• Injection Site Reactions: Common; inspect for erythema, swelling, nodules.
• QT Prolongation: Caution in patients with cardiovascular disease or on QT‑prolonging agents; periodic ECG recommended.
• Hypersensitivity Reactions: Rare; monitor during and after injection.
• Osteoporosis Risk: Long-term ADT increases fracture risk; monitor bone mineral density and consider supplementation.
• Tumour Flare Avoidance: Degarelix avoids flare effects seen with GnRH agonists.
• Monitoring: Regular testosterone, PSA, LFTs, and heart rhythm monitoring advised.

Common (≥10%):

• Injection site reactions (pain, erythema, swelling, nodules)
• Hot flashes
• Elevated liver enzymes
• Weight gain
• Increased ALT/AST

Less Common (1–10%):

• Erectile dysfunction
• Decreased libido
• Fatigue
• Arthralgia
• Back pain

Serious/Rare:

• QT prolongation and arrhythmias
• Severe allergic reactions (e.g., anaphylaxis)
• Elevated liver enzymes leading to hepatic dysfunction
• Cardiovascular events (e.g., hypertension, myocardial ischemia)

Timing:

• Injection site reactions occur early and may diminish with time; metabolic side effects often develop over weeks to months.

• QT-prolonging drugs (e.g., antiarrhythmics, antipsychotics): Increased risk of arrhythmia.
• No significant CYP interactions since degarelix is not metabolized via P450.
• Other ADT agents: May have additive androgen suppression; adjust combination therapy carefully.
• Alcohol: No direct interaction but may exacerbate hot flashes or cardiovascular risks.

• 2022–2024 Prostate Cancer Guidelines (NCCN, EAU): Include degarelix as an option for initial ADT—especially in patients requiring rapid testosterone suppression or at risk of flare.
• European and American societies emphasize degarelix for patients with spinal metastases or severe symptoms.
• Cardiovascular Safety: Data showing lower rates of cardiovascular events compared to GnRH agonists in high-risk patients are increasingly recognized.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze.
• Protect from light; keep in original carton until use.
• Once removed from refrigeration, use within 30 days at temperatures up to 25°C.
• Handling: Inspect solution before administration; discard if particulate or discolored.