degarelix

Trade Name:

Firmagon®

Appearance:

Clear solution

Monograph Name:

degarelix

Monograph Body:

Drug Monograph

A - Drug Name

degarelix

COMMON TRADE NAME(S): Firmagon®

B - Mechanism of Action and Pharmacokinetics

Degarelix, a synthetic decapeptide is a gonadotropin-releasing hormone (GnRH) receptor antagonist and reduces the release of LH/FSH. Unlike earlier compounds, degarelix has only weak histamine releasing activity.

Marketing approval was based on testosterone suppression to castrate levels over a 1 year treatment period. Evidence of palliation of improved survival has not been demonstrated.

Absorption

Linear pharmacokinetics with no accumulation. Pharmacokinetics dependent upon concentration at injection site (↓ exposure with ↑ concentration).

Distribution

Distributed throughout total body water

Cross blood brain barrier?

No information found.

PPB

90% (alpha-glycoprotein and albumin)

Metabolism

Undergoes hydrolysis by peptidases and proteases in the hepatobiliary system. Not a substrate, inducer, nor inhibitor of CYP 450 or p-glycoprotein.

Active metabolites

Inactive metabolites

Peptide fragments

Elimination

Biphasic elimination

Half-life

43 days(starting dose); 31 days (maintenance dose)

Urine

20-30% (unchanged)

Clearance

Hepatobiliary: 70-80%

Clearance

35-50 mL/h/kg

C - Indications and Status

Health Canada Approvals:

Prostate cancer

Refer to the product monograph for a full list and details of approved indications.

D - Adverse Effects

Emetogenic Potential:

Not applicable

Extravasation Potential: None

The following table contains adverse effects reported mainly in the controlled study at the recommended dose.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arterial thromboembolism (1%)	E
	Atrioventricular block (rare)	E
	Hypertension (6%)	E
	QT interval prolonged (20%)	E
Gastrointestinal	Constipation (5%)	E
	Diarrhea	I E
	Nausea (4%)	I
	Weight gain (9%)	E
General	Fatigue (3%)	E
	Flu-like symptoms (5%)	I
Hematological	Anemia (3%)	E
Hepatobiliary	↑ LFTs (10%) ( <1% Grade 3)	E
Hypersensitivity	Hypersensitivity (rare)	I
Immune	Antibody response (46%)	D
Injection site	Injection site reaction (35%) (2% severe)	I
Metabolic / Endocrine	Abnormal electrolyte(s)	E
	↑ Cholesterol (3%)	E
	Hyperglycemia	E
Musculoskeletal	Muscle weakness (less common)	E
	Musculoskeletal pain (6%)	E
	Osteoporosis (3%)	D
Nervous System	Dizziness (<5%)	E
	Headache (<5%)	E
	Insomnia (<5%)	E
Renal	Creatinine increased (2%)	E
Reproductive and breast disorders	Androgen deprivation symptoms (26%) (hot flashes, erectile dysfunction, gynecomastia)	E
Urinary	Urinary symptoms (5%) (including infection)	E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common side effects for degarelix include injection site reaction, androgen deprivation symptoms, QT interval prolonged, ↑ LFTs, weight gain, hypertension, musculoskeletal pain, constipation and flu-like symptoms.

Pain, erythema, swelling, nodule and induration were the most common injection site reactions and primarily occurred with the first dose. These reactions were mostly transient and usually resolved after a few days. Reported serious injection site reactions include injection site infection, abscess and necrosis that could require surgical treatment/drainage.

Mild, transient increases in LFTs have been observed, and were not accompanied by a rise in bilirubin or clinical symptoms.

Men treated with androgen deprivation (including orchiectomy, GnRH agonists and antiandrogens) are at increased risk of developing heart disease, QTc prolongation, poor glucose tolerance and osteoporosis. However, degarelix has no intrinsic effect on the QTc.

Anti-degarelix antibodies are commonly reported but do not seem to have any clinical sequelae on safety or efficacy.

E - Dosing

Refer to protocol by which patient is being treated.

Adults:

Starting dose: 240 mg subcut once (given as 2 x 120 mg injections at 40 mg/mL)

One month later, start:

Maintenance: 80 mg subcut (1 injection at 20 mg/mL) monthly

Dosage with Hepatic Impairment:

Although drug exposure is 10-18% lower in mild to moderate hepatic impairment, no dosage adjustment is required in these patients. Exercise caution in patients with severe hepatic impairment as no studies have been conducted in this population.

Dosage with Renal Impairment:

Drug clearance decreases by 23% in patients with moderate renal impairment (< 50 mL/min); however, no dosage adjustment is required in mild to moderate renal impairment. Exercise caution in patients with severe renal impairment as there is insufficient data available in this population.

Dosage in the elderly:

No dose adjustment required.

Children:

Not indicated for use in patients < 18 years of age.

F - Administration Guidelines

Outpatient prescription for administration at Cancer Centre or at physician’s office.
For subcutaneous injection in the abdomen.
Dosage strength and concentration of injection differ between starting and maintenance doses. The concentrations recommended in the dosing section should be used, since the pharmacokinetics of degarelix are strongly concentration-dependent.
Gloves should be worn during preparation and administration.
Reconstitute using sterile water for injection (SWI) as directed in the product monograph. Reconstitution procedure may take up to 15 minutes.
Do not shake the vial(s). Swirl gently during reconstitution.
Resulting solution should be clear and free of undissolved powder or particles.
Reconstituted product must be administered within 2 hours after addition of SWI.
Ensure injection site is free of pressure from belts, waistbands, other clothing, or ribs. Rotate injection sites.
For further details regarding proper reconstitution of degarelix, refer to the most updated Product Monograph.

G - Special Precautions

Contraindications:

Patients who have hypersensitivity to degarelix or to any of its excipients.

Other Warnings/Precautions:

Fatigue and dizziness are common adverse reactions with degarelix and caution must be exercised with driving and operating machines.
Long-term androgen deprivation prolongs the QT interval. Although a thorough QT study showed that there was no intrinsic effect of degarelix on heart rate, QT/QTc, PR intervals, QRS duration, or T or U wave morphology in healthy men, caution should be exercised in patients with congenital long QT syndrome, electrolyte abnormalities, congestive heart failure, and in patients taking antiarrhythmic medications.

Other Drug Properties:

Carcinogenicity: Yes

Pregnancy and Lactation:

Mutagenicity: No
Genotoxicity: No information available
Embryotoxicity: Yes
Fetotoxicity: Yes
Pregnancy:
Degarelix is contraindicated in patients who are or may become pregnant. Adequate contraception should be used during treatment, and for at least 6 months after the last dose. (general recommendation)
Breastfeeding:
Degarelix is only indicated in patients with prostate cancer. There are no data on the presence of degarelix in human milk.
Fertility effects: Probable

Documented in animal studies

H - Interactions

Clinically significant drug-drug interactions are unlikely other than those listed below.

Degarelix suppresses the pituitary-gonadal axis. Results of diagnostic tests for pituitary or gonadal functions may be affected.

AGENT	EFFECT	MECHANISM	MANAGEMENT
Drugs that may prolong QT (i.e. Amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc)	↑ risk of QT interval prolongation	Additive	Caution; monitor closely.

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
Creatinine	Baseline and as clinically indicated.
Electrolytes, including calcium, magnesium, potassium, sodium	Baseline and as clinically indicated.
Liver function tests	Baseline and as clinically indicated.
Blood glucose	Baseline and as clinically indicated.
ECG	Baseline and as clinically indicated.
Testosterone concentrations	In patients with hepatic impairment: monthly until medical castration is achieved then every 2 months.
Clinical assessment for local reactions, diabetes, osteoporosis, cardiovascular changes, hot flashes	Baseline and as clinically indicated.

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Supplementary Public Funding

ODB - General Benefit (ODB Formulary )

degarelix ()

K - References

Degarelix acetate: e-AHFS. Accessed December 30, 2009.

Frampton JE and Lyseng-Williamson KA. Degarelix. Drugs 2009; 69(14): 1967-76.

Prescribing Information: Firmagon® (degarelix acetate). Ferring Pharmaceuticals Inc. (US), Feb 2009.

Product Monograph: Firmagon® (degarelix acetate). Ferring Pharmaceuticals, March 18, 2016.

February 2025 Updated Pregnancy and Lactation section

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

degarelix (patient)

Info Sheet Introduction:

For treating prostate cancer.

Info Sheet Date: Tuesday, August 14, 2018 Info Sheet body:

Medication Information Sheet

degarelix (DEG-a-REL-ix)

This document provides general information about your medication. It does not replace the advice of your health care professional. Always discuss your therapy with your health care professional and refer to the package insert for more details.

Other Name: Firmagon®

Appearance:

Clear solution

What is this medication for?

For treating prostate cancer.

What should I do before I have this medication?

Tell your health care team if you have/had significant medical condition(s), especially if you have / had:
- Heart problems (including irregular heartbeat)
- Bone problems or thinning
People who have cancer are at a higher risk of developing other cancers. Also, some cancer medications may increase this risk. You should discuss this with your doctor.

How will this medication affect sex, pregnancy and breastfeeding?

While this may not be directly applicable to you, if there is any chance that your female partner may become pregnant, you and your partner together must:
- ► Use 2 effective forms of birth control at the same time while taking this drug. Keep using birth control for at least 6 months after your last dose unless your health care team told you differently. Talk to your health care team to figure out the best method(s) for you and/or your partner.
Let your health care team know if your partner is pregnant or becomes pregnant during your degarelix treatment.
This medication may affect fertility (ability to get your female partner pregnant).

How is this medication given?

This drug is given by injection under the skin. Do not use pressure (waist band or belt) on the part where the shot is given.
Your doctor or nurse will give this drug. Be sure to visit your doctor for your repeat injection. Speak to your health care professional to see what drugs and supplies you need to bring for your next visit.

What else do I need to know while on this medication?

This medication can interact with other medications and can result in the treatment not working as well or cause severe side effects.
Make sure your health care team knows about all your medications (prescription, over-the-counter, herbals and supplements). Check with your health care team before starting or stopping any of them.
For mild aches and pain or fever:
- If you feel unwell, take your temperature before taking any medications for pain or fever. They may hide a fever.
- You may take acetaminophen (Tylenol®) tablets. Ask your health care team about the right dose for you.
- Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or aspirin (acetylsalicylic acid, ASA), including low dose aspirin for heart conditions, may increase your chance of bleeding. Talk to your health care team before you start or stop these medications.
- Talk to your health care team or go to the closest emergency room right away if you have a fever. See the Fever pamphlet for more information.

Degarelix may cause dizziness. Do not drive a car or operate machinery until you know how the drug affects you.

How should I safely store this medication?

Keep this medication in the original packaging at room temperature in a dry place, away from heat and light. Keep out of sight and reach of children and pets.
Do not throw out any unused medications at home. Bring them to your pharmacy to be thrown away safely.

What are the side effects of this medication?

You may not have all of the side effects below. You may have side effects that are not listed.

Side effects and what to do	When to contact doctor?
Common Side Effects (in 25 to 49 out of 100 people)

Reactions at the injection site

Watch for pain, redness, itchiness, bruising, mild rash or swelling.

Contact your health care team if no improvement or if severe

Hot flashes, feeling or wave of warmth

You may sweat more or have trouble sleeping because of this.

To help prevent hot flashes :

Avoid triggers such as spicy food, alcohol and caffeine (tea, coffee, and soft drinks),
Exercise regularly. Ask your health care team what exercises are appropriate for you before you start any new exercise.
Quitting smoking may also help.

If you have hot flashes :

Keep cool; dress lightly or in layers that you can easily remove and drink plenty of liquids unless you have been told otherwise.
Hot flashes may improve over time. Talk to your health care team if this is bothersome for you.

Other symptoms of having low testosterone levels

Decreased sexual function or desire to have sex
Breast swelling or tenderness
Low energy
Mood changes, depression
Thinning of the bone which may be severe and lead to fractures
High cholesterol and effects on your heart

Contact your health care team if these feelings bother you.

Contact your health care team if no improvement or if severe

Side effects and what to do	When to contact doctor?
Less Common Side Effects (in 10 to 24 out of 100 people)

Heart problems

You may have an irregular heartbeat, shortness of breath, chest pain, fainting spells or swelling in your legs, ankles and belly.

Get emergency medical help right away

Abnormal liver lab tests

You may have yellowish skin or eyes, unusually dark pee or pain on the right side of your belly. Talk to your health care team if this happens.
Your doctor may monitor your liver regularly with a blood test.

Contact your health care team if no improvement or if severe

Other rare, but serious side effects are possible.
If you experience ANY of the following, speak to your cancer health care provider or get emergency medical help right away:

Sudden loss of vision, speech, or the use of your limb(s), pain in belly or limb.
Fever, severe rash, itchiness, flushing, dizziness, shortness of breath, chest or throat tightness.

For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

degarelix patient.pdf Info Sheet (French):

dgarlix pour le patient.pdf Monograph:

degarelix.pdf Funding Program: ODB - General Benefit Funding Instance:

degarelix

Phonetic Spelling:

DEG-a-REL-ix

Cancer Type: Genitourinary Prostate Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Tuesday, February 18, 2025 Universal Date: 2025-02-18 00:00:00 AddThis: Title URL: degarelix Drug Display Status: Active Revision Summary:
Drug Monograph: Updated Pregnancy and Lactation section