DEGARELIX ACETATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEGARELIX ACETATE (DEGARELIX ACETATE).
Gonadotropin-releasing hormone (GnRH) receptor antagonist; competitively and reversibly binds to GnRH receptors in the anterior pituitary, rapidly suppressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, thereby reducing testosterone production.
| Metabolism | Hepatic via hydrolysis of the acetate ester; no significant CYP450 involvement. |
| Excretion | Renal elimination accounts for approximately 20-30% of the dose as unchanged drug; fecal elimination accounts for 70-80% primarily as metabolites. |
| Half-life | Terminal elimination half-life is approximately 43-73 days after subcutaneous administration, reflecting slow release from the depot formulation. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 1 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Subcutaneous: approximately 100% for the depot formulation; not available orally due to peptide degradation. |
| Onset of Action | Subcutaneous: suppression of testosterone to castrate levels (≤0.5 ng/mL) occurs within 3 days in most patients; maximal effect by day 28. |
| Duration of Action | Subcutaneous: Testosterone suppression persists for at least 28 days with monthly dosing; recovery of testosterone to normal levels may take several months after discontinuation. |
Subcutaneous injection: 240 mg loading dose (two 120 mg injections) on day 1, followed by 80 mg every 28 days.
| Dosage form | NJECTION, POWDER, LYOPHILIZED, FOR SOLUTION |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. Insufficient data for GFR <15 mL/min or dialysis; use caution. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dosing. |
| Geriatric use | No specific dose adjustment required; similar efficacy and safety observed in elderly patients (≥65 years) compared to younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEGARELIX ACETATE (DEGARELIX ACETATE).
| Breastfeeding | No data available on excretion in human milk; potential for serious adverse effects in nursing infants; discontinue breastfeeding or discontinue drug. |
| Teratogenic Risk | Category X: Contraindicated in pregnancy. First trimester: Risk of spontaneous abortion and congenital anomalies due to hormonal disruption. Second and third trimesters: Potential for fetal androgen deprivation leading to ambiguous genitalia in male fetuses. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to degarelix or any component of the formulation","Pregnancy (potential fetal harm)"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis and angioedema","QT interval prolongation","Laboratory test interference with gonadotropin and gonadal steroid assays","Injection site reactions including pain and erythema","Bone density loss","Hyperglycemia and increased risk of diabetes"] |
Loading safety data…
| Pregnancy test before initiation; monitor for signs of fetal distress if inadvertent exposure; ultrasound for fetal development if exposure occurs. |
| Fertility Effects | Suppresses spermatogenesis and may impair fertility in males; effects are reversible upon discontinuation. In females, inhibits ovulation; effects reversible. |