Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist used in the treatment of advanced prostate cancer. It works by quickly decreasing the levels of certain hormones (testosterone) in the body. This reduction in testosterone can slow or stop the growth of prostate cancer cells.

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:

Degarelix is administered subcutaneously (under the skin) in the treatment of advanced prostate cancer as follows:

• Loading dose: 240 mg, which is given as two separate injections of 120 mg each.
• Maintenance dose: After the loading dose, the patient typically receives 80 mg every 28 days (4 weeks). This dose is administered as a single injection.

The initial loading dose helps to rapidly reduce testosterone levels, and the subsequent maintenance doses ensure that the testosterone levels remain suppressed over time.

Firmagon (Degarelix) Dose in Childrens

It is not indicated for use in children.   

Pregnancy Risk Factor X

• Women who are pregnant or might get pregnant shouldn't use it.
• Tests on animals showed it can harm unborn babies.

Use Degarelix while breastfeeding

• We don't know if degarelix passes into breast milk.
• This medicine isn't meant for women.

Firmagon Dose in kidney impairment:

• If your kidneys filter 50 to 80 mL per minute, you don't need to change the dose.
• If it's less than 50 mL per minute, the maker of the drug doesn't give specific guidance, so be careful using it.

Firmagon Dose in liver disease:

• If you have mild to medium liver problems (classed as A and B): You don't need to change the dose, but keep an eye on testosterone levels in the blood.
• If you have serious liver problems (classed as C): The drug maker doesn't give specific advice because it hasn't been fully studied, so be careful using it.

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:

• Don't use degarelix if you're allergic to it or any of its ingredients. Also, women who are pregnant or might get pregnant shouldn't use it.
• We're not sure if being allergic to one drug in this group means you'll be allergic to others like it. But since they're similar, it's possible. So, be cautious.

Warnings & Precautions

Anemia

• Low testosterone can lead to low red blood cell counts, which is called anemia.

Reduced bone mineral density

• Treatments that lower male hormone levels can make bones weaker.

Hypersensitivity

• Some people have severe allergic reactions to this medicine, like sudden and serious swelling or rashes.
• If this happens, stop using it right away (even if you haven't given the full dose).
• Treat the allergic reaction as your doctor advises.
• Don't use the medicine again if you've had a serious allergic reaction to it.

Extension of QT

• This treatment can make the heartbeat irregular in a specific way called "QT prolongation".
• Be careful using it for people who already have heart rhythm issues, take certain other medicines, have heart failure, or imbalanced body salts.
• It might be good to check heart rhythms and salt levels in the blood from time to time.

Cardiovascular disease

• Treatments that lower male hormone levels might raise the chances of heart problems.

Diabetes:

• Treatments that lower male hormone levels might increase the risk of getting diabetes or make the body less responsive to insulin.

Hepatic impairment

• In people with liver problems, the body doesn't use degarelix as much.
• But for those with mild to medium liver issues, there's no need to change the dose.
• Still, it's good to check their testosterone levels.
• For people with serious liver problems, be careful using it because we're not sure how it will affect them.
• Also, there have been slight, short-term increases in some liver tests.
• So, keep an eye on liver health if there are known liver issues or concerns.

Renal impairment

• We don't have much information on how this drug works in people with moderate to serious kidney problems.
• So, if their kidneys don't filter blood well (less than 50 mL per minute), be careful using the drug.

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

Risk Factor C (Monitor therapy).
Haloperidol	QT-prolonging agents (Indeterminate risk - Caution), may increase the QTcprolonging effects of Haloperidol.
Agents that prolong QT (Highest risk)	QT-prolonging agents (Indeterminate risk - Caution), may increase the QTc prolonging effect of QT Prolonging Agents. When using these agents together, be sure to monitor for QTc interval prolongation or ventricular arrhythmias. Patients at higher risk for QTc prolongation might have additional risk factors.
Risk Factor X (Avoid Combination)
Indium 11 Capromab Pendetide	Antigonadotropic Agents can reduce the diagnostic effectiveness of Indium 111Capromab Pendetide.

Monitor:

• Prostate Health:
  • Check PSA (a marker for prostate health) regularly.
  • If PSA goes up, check testosterone levels.
• For Those with Liver Issues:
  • Check testosterone levels monthly until they're low enough, then maybe every other month.
• Liver Health:
  • Check liver function before starting treatment.
• Electrolytes:
  • Think about checking calcium, magnesium, potassium, and sodium levels before and during treatment.
• Heart Health:
  • Consider checking the heart's rhythm (ECG) before and during treatment.
• Bone Health:
  • Think about checking bone strength.

Before Starting Treatment:

• Diabetes and Heart Risks:
  • Check blood pressure, blood fats (lipid profile), and blood sugar.
  • Recheck these 3 to 6 months after starting treatment.

How to administer Degarelix (Firmagon)?

Where to Inject:

• Use the belly area.

How to Do It:

• Pinch the skin to lift up the fatty layer.
• Put the needle in at a 45-degree angle.

Before Injecting:

• Pull back on the plunger a little to check for blood (this is called aspiration).
• If you see blood in the syringe, don't use it. Throw it away and prepare a new dose.

Injecting the Drug:

• Push the medicine in slowly, over 30 seconds.
• Pull out the needle and then let go of the skin.

Important Notes:

• Only use under the skin (SubQ), not in a vein or muscle.
• Don't give the shot where clothes might press on it, like near the waistband, belt, or close to the ribs.
• Use a different spot each time.

Dosing Instructions:

• First Dose (Loading Dose): Give two shots, each with 3 mL (40 mg/mL). Use two different spots.
• Regular Dose (Maintenance Dose): One shot with 4 mL (20 mg/mL), starting 28 days after the first dose.

Degarelix (Firmagon) Mechanism of action:

Target and Action:

• This drug targets a part of the brain called the anterior pituitary gland.
• It blocks a receptor there for a hormone called GnRH (gonadotropin-releasing hormone).

What It Does:

• When it blocks the receptor, it slows down the release of two other hormones: LH (luteinizing hormone) and FSH (follicle-stimulating hormone).

Result:

• By doing this, it reduces the production of testosterone (a male hormone) quickly.
• Testosterone levels drop because less LH and FSH are around to signal the body to make testosterone.

No Flare-Up:

• Unlike some other treatments, it doesn't cause a sudden increase in testosterone before it starts working.

Starts Working Fast:

• It acts quickly. In most patients (about 96%), testosterone drops to low levels within 3 days.

Where It Goes in the Body (Distribution):

• The drug spreads widely in the body, over 1000 liters.

How Much Sticks to Proteins:

• About 90% of the drug binds to proteins in the blood.

How It's Broken Down (Metabolism):

• It's mainly processed in the liver and breaks down into smaller pieces.

How It's Released:

• After injection, it's released in two phases. There's a quick release, and then it's slowly released from the injection spot.

Effect of Liver Problems:

• If someone has mild to moderate liver issues, their body absorbs less of the drug.

How Long It Lasts (Half-life):

• After the first dose (loading dose), it lasts about 53 days in the body.
• With regular doses (maintenance dose), it lasts about 31 days.

Peak Levels:

• The drug reaches its highest level in the blood within 2 days after the first dose.

How It Leaves the Body (Excretion):

• It mainly goes out with the feces (70-80%), mostly in broken-down form.
• Some (20-30%) is excreted in the urine.

International Brands of Degarelix:

• Firmagon
• Gonax

Degarelix Brand Names in Pakistan:

Not available.