Version May 2024
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 50 to 80 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (data are limited); use with caution.
Mild to moderate hepatic impairment (Child Pugh classes A and B): No dosage adjustment necessary; monitor serum testosterone levels (hepatic impairment may lower degarelix exposure).
Severe hepatic impairment (Child Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Hypersensitivity: Manage hypersensitivity as clinically indicated. Discontinue degarelix for serious hypersensitivity reaction (immediately if dose not fully injected); do not rechallenge.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hot flash (26%), increased gamma-glutamyl transferase (≥10%)
Hepatic: Increased serum transaminases (≥10%)
Local: Injection site reaction (35%; including erythema at injection site [17%], induration at injection site [4%], injection site nodule [3%], pain at injection site [28%], swelling at injection site [6%])
1% to 10%:
Cardiovascular: Hypertension (6%)
Dermatologic: Diaphoresis (≥1%)
Endocrine & metabolic: Gynecomastia (≥1%), weight gain (9%)
Gastrointestinal: Constipation (5%), diarrhea, (≥1%), nausea (1% to <5%)
Genitourinary: Erectile dysfunction (≥1%), testicular atrophy (≥1%), urinary tract infection (5%)
Immunologic: Antibody development (antidegarelix: 10%)
Nervous system: Chills (5%), dizziness (1% to <5%), fatigue (1% to <5%), headache (1% to <5%), insomnia (1% to <5%)
Neuromuscular & skeletal: Arthralgia (5%), asthenia (1% to <5%), back pain (6%)
Miscellaneous: Fever (1% to <5%), night sweats (1% to <5%)
<1%: Cardiovascular: Prolonged QT interval on ECG
Frequency not defined: Hepatic: Abnormal liver function tests
Postmarketing: Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, urticaria, and angioedema)
History of severe hypersensitivity to degarelix or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity: Hypersensitivity reactions (including anaphylaxis, urticaria, and angioedema) have been reported.
• QT prolongation: Androgen deprivation therapy may prolong the QT interval. Assess potential risks versus potential benefits in patients with congenital long QT syndrome, known history of QT prolongation, or other risk factors for QT prolongation (eg, concomitant use of medications known to prolong QT interval, heart failure, and/or electrolyte abnormalities).
Disease-related concerns:
• Bone mineral density: Androgen deprivation therapy is associated with decreased bone mineral density.
• Cardiovascular disease: Androgen deprivation therapy may increase the risk for cardiovascular disease (Levine 2010).
• Diabetes: Androgen deprivation therapy may be associated with an increased risk for insulin resistance and diabetes (Keating 2006).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous, as acetate:
Firmagon: 80 mg (1 ea)
Firmagon (240 MG Dose): 120 MG (1 ea)
No
Solution (reconstituted) (Firmagon (240 MG Dose) Subcutaneous)
120 mg/vial (per each): $914.51
Solution (reconstituted) (Firmagon Subcutaneous)
80 mg (per each): $586.14
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous, as acetate:
Firmagon: 80 mg (1 ea); 120 mg (1 ea)
SUBQ: For SUBQ administration only; do not inject into a vein or into muscle. Administer (deep) SUBQ in the abdominal area by pinching skin and elevating SUBQ tissue; insert needle at a 45 degree angle. Gently pull plunger back to check for aspiration (if blood is aspirated into syringe, do not inject; discard and reconstitute a new dose); slowly inject over 30 seconds, remove needle and then release skin. Avoid pressure exposed areas (eg, waistband, belt, or near ribs). Rotate injection site. Advise patients to avoid rubbing or scratching injection site area.
The loading dose is administered as two 3 mL injections (40 mg/mL) in different sites. The maintenance dose is administered as a single 4 mL injection (20 mg/mL); begin maintenance dose 28 days after initial loading dose.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Prostate cancer, advanced: Treatment of advanced prostate cancer.
Degarelix may be confused with cetrorelix, elagolix, ganirelix, relugolix
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Flotufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Flotufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of ADT on the performance of flotufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Gallium Ga 68 PSMA-11: Androgen Deprivation Therapy Agents may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact of ADT on the performance of gallium Ga 68 PSMA-11 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Indium 111 Capromab Pendetide: Antigonadotropic Agents may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Piflufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Piflufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of ADT on the performance of piflufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Degarelix may impair fertility in males and females (based on the mechanism of action). Use of degarelix for ovarian suppression is under study (Dellapasqua 2019; Papanikolaou 2018).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to degarelix may cause fetal harm.
It is not known if degarelix is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
Prostate-specific antigen (PSA) periodically, serum testosterone levels (if PSA increases; in patients with mild or moderate hepatic impairment,: monitor testosterone levels monthly until achieve castration levels, then consider monitoring every other month), liver function tests (at baseline and periodically in patients with suspected hepatic dysfunction); consider baseline and periodic monitoring of serum electrolytes (calcium, magnesium, potassium, sodium). Consider baseline and periodic ECG monitoring. Monitor bone mineral density. Monitor for signs/symptoms of hypersensitivity.
Screen for diabetes and cardiovascular risk (blood pressure, lipid profile, serum glucose) prior to initiating treatment and 3 to 6 months after initiation (Levine 2010).
Cardiovascular monitoring for patients with prostate cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; baseline and serial ECGs are recommended in patients at risk of QTc prolongation during androgen deprivation therapy (ADT); estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually during ADT (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist which reversibly binds to GnRH receptors in the anterior pituitary gland, blocking the receptor and decreasing secretion of luteinizing hormone (LH) and follicle stimulation hormone (FSH), resulting in rapid androgen deprivation by decreasing testosterone production, thereby decreasing testosterone levels. Testosterone levels do not exhibit an initial surge, or flare, as is typical with GnRH agonists (Crawford 2011).
Onset of action: Rapid; ~96% of patients had testosterone levels ≤50 ng/dL within 3 days (Klotz 2008).
Distribution: Vd: >1,000 L.
Protein binding: ~90%.
Metabolism: Hepatobiliary, via peptide hydrolysis.
Bioavailability: Biphasic release: Rapid release initially, then slow release from depot formed after subcutaneous injection administration (Tornoe 2007). Bioavailability is decreased in patients with mild-to-moderate hepatic impairment.
Half-life elimination: Loading dose: SUBQ: ~53 days; Maintenance dose: SUBQ: ~31 days (Canadian labeling).
Time to peak, plasma: Loading dose: SUBQ: Within 2 days.
Excretion: Feces (~70% to 80%, primarily as peptide fragments); urine (~20% to 30%, as unchanged drug).
Clearance: ~9 L/hour.
Hepatic function impairment: Based on a single 1 mg IV degarelix dose in subjects without prostate cancer with mild (Child Pugh class A) or moderate (Child Pugh class B) impairment, degarelix exposure was decreased 10% for mild impairment, and 18% for moderate impairment (when compared to subjects without prostate cancer with normal hepatic function).
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