DEGARELIX ACETATE
Clinical safety rating
cautionComprehensive clinical and safety monograph for DEGARELIX ACETATE (DEGARELIX ACETATE).
Comprehensive clinical and safety monograph for DEGARELIX ACETATE (DEGARELIX ACETATE).
Treatment of advanced prostate cancer
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. |
| Molecular Weight | 884.2 |
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 | Contraindicated due to risk of fetal harm; animal studies show teratogenicity and pregnancy loss. |
| 2nd trimester | Contraindicated due to risk of fetal harm; androgen deprivation may affect fetal development. |
| 3rd trimester | Contraindicated due to risk of fetal harm; potential for androgen receptor blockade effects on fetus. |
Clinical note
Comprehensive clinical and safety monograph for DEGARELIX ACETATE (DEGARELIX ACETATE).
| Placental transfer | Crosses placenta in animal studies; unknown in humans but expected based on molecular weight and mechanism. |
| Breastfeeding | Not recommended during breastfeeding; drug may be excreted in human milk and could cause adverse effects in the infant. |
| Lactation Rating | L5 - Contraindicated |
| 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 | 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to degarelix or any component of the formulationPregnancy
| 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 |
| Food/Dietary | No specific food interactions have been identified. Degarelix is administered parenterally and does not interact with dietary components. Avoid grapefruit juice if concurrent QT-prolonging drugs are used, but not a direct interaction with degarelix. |
| Clinical Pearls | Degarelix acetate is a GnRH antagonist used for advanced prostate cancer. It provides rapid testosterone suppression without the initial testosterone surge seen with GnRH agonists. Monitor serum testosterone and PSA levels; castrate levels (<50 ng/dL) typically achieved within 3 days. Injection site reactions are common; rotate injection sites (abdomen, thigh, buttock). Avoid in patients with known QT prolongation or concurrent QT-prolonging drugs. Contraindicated in women and children. |
| Patient Advice | Degarelix is given as a subcutaneous injection by a healthcare provider every month (or every 2 months for maintenance dose) to treat advanced prostate cancer. · Do not miss scheduled injections because consistent dosing is needed to keep testosterone levels low. · Common side effects include injection site pain, redness, or swelling; hot flashes; increased liver enzymes; and weight gain. · Report signs of allergic reaction (rash, itching, difficulty breathing) or prolonged QT interval (fainting, palpitations) to your doctor immediately. · Degarelix may cause bone thinning; discuss calcium and vitamin D supplementation with your doctor. · This drug can cause harm to a fetus; not for use in women or children. |
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