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Degarelix

Pronunciation

(deg a REL ix)

Index Terms

  • Degarelix Acetate
  • FE200486

Dosage Forms

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)

Brand Names: U.S.

  • Firmagon

Pharmacologic Category

  • Antineoplastic Agent, Gonadotropin-Releasing Hormone Antagonist
  • Gonadotropin Releasing Hormone Antagonist

Pharmacology

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).

Distribution

Vd: >1000 L

Metabolism

Hepatobiliary, via peptide hydrolysis

Excretion

Feces (~70% to 80%, primarily as peptide fragments); urine (~20% to 30%)

Onset of Action

Rapid; ~96% of patients had testosterone levels ≤50 ng/dL within 3 days (Klotz 2008)

Time to Peak

Plasma: Loading dose: SubQ: Within 2 days

Half-Life Elimination

Loading dose: SubQ: ~53 days

Protein Binding

~90%

Special Populations: Hepatic Function Impairment

A single dose of degarelix 1 mg was administered intravenously to 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 patients without prostate cancer and with normal hepatic function).

Use: Labeled Indications

Prostate cancer, advanced: Treatment of advanced prostate cancer

Contraindications

Known hypersensitivity to degarelix or any component of the formulation; women who are or may become pregnant.

Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity can not be ruled out with certainty.

Dosage

Prostate cancer, advanced: Adults: SubQ:

Loading dose: 240 mg administered as two 120 mg (3 mL) injections

Maintenance dose: 80 mg administered as one 4 mL injection every 28 days (beginning 28 days after initial loading dose)

Dosage adjustment in renal impairment:

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; use with caution.

Dosage adjustment in hepatic impairment:

Mild-to-moderate hepatic impairment: No dosage adjustment necessary; monitor serum testosterone levels

Severe hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]); wear gloves for preparation and administration. Reconstitute with provided prefilled syringe containing preservative free sterile water for injection (reconstitute each 120 mg vial with 3 mL; reconstitute the 80 mg vial with 4.2 mL). Swirl gently; do not shake (to prevent foaming). Dissolution usually takes a few minutes, although may take up to 15 minutes. May tilt the vial slightly if the powder adheres to the side of the vial. To withdraw for administration, turn the vial completely upside down and pull down on the plunger to withdraw all of the reconstituted solution from the vial to the syringe; expel all air bubbles. Administer within 1 hour of reconstitution. Use of concentrations other than those described in the manufacturer’s labeling is not recommended.

Administration

Administer (deep) SubQ in the abdominal area by pinching skin and elevating SubQ tissue; insert needle at a 45 degree angle. Slowly inject over 30 seconds. For SubQ administration only; do not inject into a vein or into muscle. Avoid pressure exposed areas (eg, waistband, belt, or near ribs). Rotate injection site. Inject loading dose as two 3 mL injections (40 mg/mL) in different sites; maintenance dose should be administered as a single 4 mL injection (20 mg/mL); begin maintenance dose 28 days after initial loading dose.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Use within 1 hour of reconstitution. Do not shake the vials.

Drug Interactions

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Indium 111 Capromab Pendetide: Antigonadotropic Agents may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination

Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Test Interactions

Suppression of pituitary-gonadal function may affect diagnostic tests of pituitary gonadotropic and gonadal functions.

Adverse Reactions

>10%:

Central nervous system: Fatigue (3% to ≥10%)

Endocrine & metabolic: Hot flash (26%), increased gamma-glutamyl transferase (≥10%), weight loss (≥10%), weight gain (9% to ≥10%)

Hepatic: Increased serum transaminases (47%)

Local: Injection site reactions (35%, grade 3: ≤2%; pain at injection site [28%], erythema at injection site [17%], swelling at injection site [6%], induration at injection site [4%], injection site nodule [3%], injection site infection [including abscess, 1%])

Miscellaneous: Fever (1% to ≥10%)

1% to 10%:

Cardiovascular: Hypertension (6%)

Central nervous system: Chills (5%), dizziness (1% to 5%), headache (1% to 5%), insomnia (1% to 5%)

Dermatologic: Diaphoresis

Endocrine & metabolic: Hypercholesterolemia (3%), gynecomastia

Gastrointestinal: Constipation (5%), nausea (1% to 5%), diarrhea

Genitourinary: Urinary tract infection (5%), erectile dysfunction, testicular atrophy

Hepatic: Increased serum ALT (10%; grade 3: <1%), increased serum AST (5%; grade 3: <1%)

Immunologic: Antibody development (antidegarelix: 10%)

Neuromuscular & skeletal: Back pain (6%), arthralgia (5%), weakness (1% to 5%)

Miscellaneous: Night sweats (1% to 5%)

<1% (Limited to important or life-threatening): Bone metastases (worsening), cerebrovascular accident, depression, hypersensitivity reaction (including anaphylaxis, urticaria, and angioedema), malignant lymphoma, mental status changes, myocardial infarction, osteoarthritis, prolonged Q-T interval on ECG, squamous cell carcinoma, unstable angina pectoris

Warnings/Precautions

Concerns related to adverse effects:

• Decreased bone mineral density: Androgen deprivation therapy is associated with decreased bone mineral density.

• Hypersensitivity: Hypersensitivity reactions (including anaphylaxis, urticaria, and angioedema) have been reported. Discontinue for serious hypersensitivity reaction (immediately if dose not fully injected); manage hypersensitivity as clinically indicated. Do not rechallenge after serious hypersensitivity reaction.

• QT prolongation: Androgen deprivation therapy may prolong the QT interval. Use with caution 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). Consider periodic electrolyte and ECG monitoring.

Disease-related concerns:

• 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).

• Hepatic impairment: Degarelix exposure is decreased in patients with hepatic impairment, dosage adjustment is not recommended in patients with mild-to-moderate hepatic impairment, although testosterone levels should be monitored. Has not been studied in patients with severe hepatic impairment; use with caution.

• Renal impairment: Data for use in patients with moderate-to-severe renal impairment (CrCl <50 mL/minute) is limited; use with caution.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Monitoring Parameters

Prostate-specific antigen (PSA) periodically, serum testosterone levels (if PSA increases; in patients with hepatic impairment: monitor testosterone levels monthly until achieve castration levels, then consider monitoring every other month), liver function tests (at baseline); consider periodic monitoring of serum electrolytes (calcium, magnesium, potassium, sodium); bone mineral density; consider periodic ECG monitoring.

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).

Pregnancy Risk Factor

X

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Use is contraindicated in women who are or may become pregnant.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience weight gain, weight loss, sexual dysfunction, decreased libido, asthenia, hot flashes, back pain, arthralgia, or chills. Have patient report immediately to prescriber arrhythmia, severe headache, significant dizziness, dysuria, difficult urination, osteodynia, or injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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