Degarelix

Usage

Degarelix is prescribed for the treatment of advanced hormone-dependent prostate cancer. It is classified as a gonadotropin-releasing hormone (GnRH) antagonist. Degarelix works by blocking GnRH receptors in the pituitary gland, thus suppressing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This leads to a significant reduction in testosterone production, inhibiting the growth of prostate cancer cells.

Alternate Names

Degarelix acetate is the active ingredient. Firmagon® is a widely recognized brand name.

How It Works

Pharmacodynamics: Degarelix competitively and reversibly binds to pituitary GnRH receptors. This action prevents the release of LH and FSH, leading to a rapid decrease in serum testosterone levels, typically below the medical castration level of 0.5 ng/mL.

Pharmacokinetics:

• Absorption: Following subcutaneous administration, degarelix reaches peak plasma concentration (Cmax) around 3 to 5 days post-injection. The initial loading dose creates an earlier onset of testosterone suppression.
• Metabolism: The metabolism of degarelix is not fully understood, however, it appears to occur through enzymatic hydrolysis at sites other than the liver, including the blood.
• Elimination: Degarelix is eliminated primarily through enzymatic hydrolysis and peptide degradation. Renal excretion is also observed although in minimal amount. The terminal half-life is about 25-30 days with repeated dosing of 80mg monthly.

Mode of Action: Degarelix acts by competitive and reversible binding to GnRH receptors in the anterior pituitary gland. This antagonism blocks the release of gonadotropins, thus reducing testosterone production. It does not cause the initial surge in testosterone (flare) seen with GnRH agonists.

Dosage

Standard Dosage

Adults:

• Initial Dose: 240 mg administered as two subcutaneous injections of 120 mg each (at a concentration of 40 mg/mL) on Day 1 in separate abdominal locations.
• Maintenance Dose: 80 mg administered as a single subcutaneous injection (at a concentration of 20 mg/mL) every 28 days, starting 28 days after the initial dose.

Children: Degarelix is not indicated for use in pediatric patients. Safety and efficacy have not been established in this population.

Special Cases:

• Elderly Patients: Dose adjustments are generally not necessary.
• Patients with Renal Impairment: For patients with mild to moderate renal impairment (creatinine clearance (CrCl) ≥50 mL/min), dose adjustment is not required. Caution should be exercised in patients with severe renal impairment (CrCl <50 mL/min).
• Patients with Hepatic Dysfunction: For patients with mild to moderate hepatic impairment, dose adjustment is not necessary. Safety and efficacy have not been established in patients with severe hepatic impairment.
• Patients with Comorbid Conditions: Use with caution in patients with congestive heart failure, heart rhythm problems (e.g., prolonged QT interval), or mineral imbalance.

Clinical Use Cases

Degarelix is specifically indicated for advanced hormone-dependent prostate cancer and is not typically used in the clinical settings you listed (Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations).

Dosage Adjustments

Dose modifications may be considered in patients with severe renal or hepatic impairment. However, data on dose adjustments for metabolic disorders or genetic polymorphisms is limited. Individualized patient factors and laboratory results should also be considered in dose adjustment decisions.

Side Effects

Common Side Effects:

• Injection site reactions (pain, erythema, swelling, induration)
• Hot flashes
• Weight gain
• Increased liver enzymes (transaminases, GGT)
• Fatigue
• Back pain

Rare but Serious Side Effects:

• Serious allergic reactions (anaphylaxis)
• QT prolongation

Long-Term Effects:

• Osteoporosis (decreased bone mineral density)
• Increased risk of diabetes

Adverse Drug Reactions (ADR):

• Severe injection site reactions (e.g., abscess, necrosis)
• Hypersensitivity reactions

Contraindications

• Hypersensitivity to degarelix or any of its components
• Women who are or may become pregnant

Drug Interactions

• Drugs that prolong the QT interval: Co-administration requires caution and may necessitate EKG and electrolyte monitoring.
• Hormonal contraceptives: Degarelix can reduce the effectiveness of birth control pills.
• CYP450 interactions: While clinically significant CYP450 interactions are considered unlikely, concomitant administration of drugs metabolized by CYP450 enzymes should be approached with caution.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: X. Degarelix is contraindicated in women who are or may become pregnant, as it can cause fetal harm.
• Breastfeeding: It is unknown if degarelix is excreted in human milk. Due to the potential for adverse reactions in nursing infants, breastfeeding should be discontinued or the drug avoided.

Drug Profile Summary

• Mechanism of Action: GnRH antagonist, suppresses LH and FSH release, leading to reduced testosterone.
• Side Effects: Injection site reactions, hot flashes, weight gain, increased liver enzymes, QT prolongation, osteoporosis.
• Contraindications: Hypersensitivity, pregnancy.
• Drug Interactions: QT prolonging drugs, hormonal contraceptives.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy; avoid or discontinue breastfeeding.
• Dosage: Initial: 240 mg (two 120 mg injections); Maintenance: 80 mg every 28 days subcutaneously.
• Monitoring Parameters: Testosterone levels, liver function tests, EKG (in patients at risk for QT prolongation), bone mineral density.

Popular Combinations

Degarelix is often used as monotherapy. Combining it with other hormonal therapies may be considered in specific cases, but requires careful assessment of potential risks and benefits.

Precautions

• General Precautions: Evaluate for hypersensitivity, heart conditions, and electrolyte imbalances.
• Pregnant Women: Contraindicated.
• Breastfeeding Mothers: Avoid or discontinue breastfeeding.
• Children & Elderly: Not for pediatric use; generally safe in elderly patients.
• Lifestyle Considerations: Alcohol consumption in moderation does not appear to significantly interact with degarelix. Advise patients to exercise caution while driving or operating machinery due to potential fatigue and dizziness.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Degarelix?

A: Initial: 240 mg (two 120 mg subcutaneous injections); Maintenance: 80 mg subcutaneously every 28 days.

Q2: What is the mechanism of action of Degarelix?

A: Degarelix is a GnRH antagonist that blocks GnRH receptors, reducing LH and FSH release, ultimately lowering testosterone production.

Q3: What are the common side effects of Degarelix?

A: Common side effects include injection site reactions, hot flashes, weight gain, and increased liver enzymes.

Q4: Is Degarelix safe to use in patients with liver or kidney problems?

A: Use with caution in patients with severe hepatic or renal impairment. Dose adjustments may be necessary.

Q5: Can Degarelix be used in women?

A: No, degarelix is contraindicated in women, especially those who are pregnant or may become pregnant.

Q6: What are the serious side effects of Degarelix?

A: Serious side effects include allergic reactions (anaphylaxis) and QT prolongation.

Q7: Does Degarelix interact with other medications?

A: It can interact with drugs that prolong the QT interval and hormonal contraceptives. Other drug interactions although deemed less likely with CYP450 interactions, warrants close monitoring. Consult resources for a comprehensive list of potential drug interactions.

Q8: What should patients be monitored for during Degarelix treatment?

A: Monitor testosterone levels, liver function, EKG (if at risk for QT prolongation), and bone mineral density.

Q9: Can a patient take Degarelix if they have a history of osteoporosis?

A: Degarelix can decrease bone density. Patients with a history of osteoporosis or at risk for developing it need monitoring of bone mineral density while on Degarelix and need to use caution.

Q10: What should a patient do if they miss a dose of Degarelix?

A: Contact their healthcare provider for instructions. A delay of 2-3 days will not significantly affect treatment efficacy, but regular administration as close to schedule as possible is recommended.