Firmagon (Degarelix) is a long-acting GnRH (Gonadotropin-releasing hormone) antagonist that is used to treat patients with advanced prostatic cancer. It achieves chemical castration that is a reduction in the testosterone levels equivalent to castration. It is a long-acting drug with effects that last for up to forty days compared to the recently developed GnRH antagonists abarelix, ganirelix, cetrorelix, and azaline B [Ref].

Firmagon (Degarelix) Vs Leuprolide:

Compared to leuprolide in a one-year phase III trial, degarelix was non-inferior in reducing serum testosterone levels. It was found to have a rapid onset of action without an ensuing testosterone surge [Ref]. Testosterone suppression to less than 0.5 ng/ml is achieved within 1 - 3 days of initiating therapy. Leuprolide suppresses the production of LH only while degarelix suppresses both LH and FSH. Degarelix reduces serum testosterone levels by more than 90% at day 3 compared to only 65% reduction by leuprolide. Combination regimens such as the addition of bicalutamide (Casodex) is not recommended.

Firmagon (Degarelix) Dose in  Adults

Firmagon (Degarelix) Dose in the treatment of advanced Prostate cancer:

• Loading dose:
  • Firmagon 240 mg is administered as two 3 ml (120 mg) injections subQ.
• Maintenance dose:
  • Firmagon 80 mg is administered as one 4 mL injection every 28 days.
  • The maintenance dose should be initiated after 28 days of the initial loading dose.

Firmagon (Degarelix) Dose in Childrens

It is not indicated for use in children.   

Pregnancy Risk Factor X

• Women who may become pregnant or are currently pregnant should not use this medication.
• In animal reproduction studies, adverse events were noted.

Use Degarelix while breastfeeding

• It is unknown if degarelix can be found in breast milk.
• This product is not recommended for women.

Firmagon Dose in kidney impairment:

• CrCl 50 - 80 mL/minute:
  • Adjustment in the dose is not necessary.
• CrCl of less than 50 mL/minute:
  • The manufacturer has not provided any adjustments in the dose.
  • It should be used with caution in these patients.

Firmagon Dose in liver disease:

• Mild to moderate (Child-Pugh classes A and B) hepatic impairment:
  • Adjustment in the dose is not necessary.
  • Serum testosterone levels should be monitored.
• Severe hepatic impairment (Child-Pugh class C):
  • It should be used with caution in patients with severe hepatic impairment as it has not been studied in these patients.

Firmagon side effects (common):

• Central Nervous System:
  • Fatigue
• Endocrine & Metabolic:
  • Hot Flash
  • Increased Gamma-Glutamyl Transferase
  • Weight Loss
  • Weight Gain
• Hepatic:
  • Increased Serum Transaminases
• Local:
  • Injection Site Reactions
    • Pain At Injection Site
    • Erythema At Injection Site
    • Swelling At Injection Site
    • Induration At Injection Site
    • Injection Site Nodule
    • Injection Site Infection
• Miscellaneous:
  • Fever

Degarelix Firmagon side effects (less common):

• Cardiovascular:
  • Hypertension
• Central Nervous System:
  • Chills
  • Dizziness
  • Headache
  • Insomnia
• Dermatologic:
  • Diaphoresis
• Endocrine & Metabolic:
  • Hypercholesterolemia
  • Gynecomastia
• Gastrointestinal:
  • Constipation
  • Nausea
  • Diarrhea
• Genitourinary:
  • Urinary Tract Infection
  • Erectile Dysfunction
  • Testicular Atrophy
• Hepatic:
  • Increased Serum ALT
  • Increased Serum AST
• Immunologic:
  • Antibody Development
• Neuromuscular & Skeletal:
  • Back Pain
  • Arthralgia
  • Weakness
• Miscellaneous:
  • Night Sweats

Contraindication to Degarelix (firmagon) Include:

• Allergy to degarelix and any component of the formulation
• Women of childbearing and pregnant women

Warnings & Precautions

• Anemia

  • Anemia is often associated with hypogonadism.
  • Check hemoglobin levels.

• Reduced bone mineral density

  • Hypogonadism causes a decrease in bone density.
  • Osteoporosis should be closely monitored.

• Hypersensitivity

  • It is possible to experience severe or life-threatening allergic reactions.
  • These include anaphylaxis and urticaria.
  • If a patient experiences hypersensitivity, they should immediately stop using the syringe.
  • Avoid retaliation with another dose.

• Extension of QT

  • Hypogonadism can lead to prolongation of the QT interval.
  • Patients with congenital long QT syndrome or history of QT prolongation should be cautious about using the drug.
  • These patients should be monitored for periodic electrolytes and ECG.

• Cardiovascular disease

  • Hypogonadism can increase the risk of developing cardiovascular disease. Patients at high risk for CAD should be cautious when taking the drug.

• Diabetes:

  • Hypogonadism (androgen withdrawal) can lead to increased insulin resistance, which may make it difficult to control diabetes.

• Hepatic impairment

  • Patients with hepatic impairment need to monitor their testosterone levels, as drug exposure in this condition is decreased.
  • Patients with mild or moderate hepatic impairment usually don't need to adjust their dose.
  • It should not be used in severe hepatic impairment.
  • Patients should be monitored regularly for transient liver function changes.

• Renal impairment

  • Patients with renal impairment (CrCl less than 50ml/min) should be cautious. There is not much data on its use in this population.

Degarelix: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• (PSA) Prostate specific antigen regularly,
• Serum testosterone levels, especially in those with hepatic impairment, are measured monthly until they drop to castration levels. Then they are checked every other month.
• Before starting therapy, liver function tests are performed.
• At baseline, serum electrolytes (calcium and magnesium, potassium, and sodium) are checked.
• Bone mineral density
• ECG monitoring at baseline, and every other month thereafter.
• Before initiating treatment, screen the patient for diabetes, other cardiovascular risk factors, such as blood pressure, cholesterol profile, and serum glucose. This is done 3 to 6 months later.

How to administer Degarelix (Firmagon)?

• It is administered subQ.
• The skin is then pinched and raised. 
• The needle is then inserted at 45°. 
• The plunger is then pulled to verify proper placement.
• If blood is taken, the needle should be pulled and the drug not injected.
• You should discard the injection and give a fresh dose.
• Do not give the dose if the needle is not in the right place.
• It shouldn't be injected directly into the veins or muscles.

Firmagon

• Injection sites should not be located near pressure sensitive areas like the waistbands, ribs and belts.
• Rotating the injection site is a good idea. 
• You should divide the loading dose into two equal parts and inject 3 ml at each site.
• A single injection of the maintenance dose of 4 mg may be made. 
• 28 days after the loading dose, the maintenance dose is administered.

Degarelix (Firmagon) Mechanism of action:

• It acts as an antagonist to Gonadotropin-releasinghormone (GnRH), which reduces testosterone production.
• It does this by binding and blocking GnRH receptors within the anterior pituitary.
• This causes a decrease in luteinizing hormone and follicle stimulating hormone (FSH), which results in rapid androgen deprivation due to decreased testosterone production.
• This drug does not cause the testosterone surge that is usually associated with GnRH antagonists.
• It is quick to start working as the serum testosterone drops below 50 ng/dl in three days. It is 90% of the time

Proteins boundIt is metabolized in the liver by hepatic hydrolysis. It is biphasic.Bioavailability. The first phase involves rapid drug release followed by slow drug release. Patients with mild-to-moderate hepatic dysfunction have lower bioavailability. Elimination of Half-lifeThe average time between a Loading dose via SubQ administration and the Maintenance dose is approximately 53 days. It takes time to get therePeak plasma concentrationAfter a loading dose, administered via subQ route, it takes less than 2 days. It is excreted mainly via feces (70-80%), and minimally via urine (20-30%).   

International Brands of Degarelix:

• Firmagon
• Gonax

Degarelix Brand Names in Pakistan:

It is not available in Pakistan.