FIRMAGON
Clinical safety rating
cautionComprehensive clinical and safety monograph for FIRMAGON (FIRMAGON).
Comprehensive clinical and safety monograph for FIRMAGON (FIRMAGON).
FDA-approved for advanced prostate cancer (hormone-sensitive, metastatic or locally advanced)Off-label: Treatment of uterine fibroids, endometriosis, and precocious puberty
Injection site reactions (pain, swelling, redness), Weight gain, Hot flashes, Increased liver enzymes, Low sexual desire, Erectile dysfunction
Gonadotropin-releasing hormone (GnRH) receptor antagonist; competitively binds to GnRH receptors in the anterior pituitary, rapidly reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, thereby suppressing testosterone production in males.
| Metabolism | Degraded into peptides and amino acids; not a substrate for CYP450 enzymes. |
| Excretion | Primarily hepatobiliary; about 90% of the dose is eliminated in feces as unchanged drug, with less than 5% excreted renally as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is approximately 63 days after subcutaneous administration in patients with prostate cancer, allowing for monthly dosing schedules. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 10 L, indicating limited extravascular distribution consistent with a large peptide. |
| Bioavailability | Subcutaneous administration: Bioavailability is approximately 50% relative to intravenous administration, with absorption characterized by a slow and sustained release profile. |
| Onset of Action | Subcutaneous injection: Suppression of testosterone to castrate levels occurs within 3 days, with maximal suppression achieved by Day 28. |
| Duration of Action | Testosterone suppression lasts for at least 56 days following a single dose of 240 mg, supporting a 1-month dosing interval; continuous suppression is maintained with repeated monthly injections. |
| Molecular Weight | 1414 |
| Action Class | GNRH antagonists |
| Brand Substitutes | Degapride 80mg Injection, Degarel 80mg Injection, Deghor 80 Injection, Degatide 80 Injection, Degalix 80 Injection, Degapride 120mg Injection, Deghor 120 Injection, Degalix 120 Injection, Degatide 120 Injection, Degrinta 120mg Injection |
For advanced prostate cancer: 120 mg subcutaneously as a loading dose (two 60 mg injections), then 80 mg subcutaneously once monthly (one 80 mg injection) starting 28 days after the loading dose.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (CrCl <30 mL/min). Use with caution. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. Not indicated for use in children. |
| Geriatric use | No specific dose adjustment is recommended for elderly patients. Monitor for cardiovascular events and changes in bone density due to androgen deprivation. |
| 1st trimester | FDA Pregnancy Category X. Animal studies and human data show fetal harm. Avoid pregnancy. GnRH antagonists increase risk of fetal loss and malformations in first trimester. |
| 2nd trimester | Category X. Avoid. Risk of fetal harm and teratogenicity. |
| 3rd trimester | Category X. Avoid. Potential fetal harm including delayed gestation and dystocia. |
Clinical note
Comprehensive clinical and safety monograph for FIRMAGON (FIRMAGON).
| Placental transfer | Readily crosses placenta in animal models; human data suggest transfer based on molecular weight and lipophilicity. |
| Breastfeeding | Not recommended. Excretion in human milk unknown, but potential for serious adverse effects in nursing infants, including hormonal disruption. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | FIRMAGON (degarelix) is contraindicated in pregnancy. GnRH antagonists like degarelix can cause fetal harm when administered to a pregnant woman. Based on findings from animal studies and its mechanism of action, degarelix is expected to increase the risk of first trimester pregnancy loss. Adequate human data are not available, but the drug should be avoided during pregnancy. If exposure occurs, inform the patient of the potential hazard. |
| Fetal Monitoring | Monitor pregnancy status in women of childbearing potential before initiation of therapy. If pregnancy is suspected, confirm with a sensitive pregnancy test and discontinue degarelix. No specific fetal monitoring is required beyond standard obstetric care if exposure occurs. |
| Fertility Effects | Degarelix suppresses pituitary gonadotropins, leading to reduced testosterone levels in males. In females, it may inhibit ovulation and reduce estrogen levels, potentially impairing fertility. These effects are generally reversible upon discontinuation. Animal studies have shown impaired fertility in both sexes. |
■ FDA Black Box Warning
Increased risk of QT interval prolongation; use caution in patients with congenital long QT syndrome, electrolyte abnormalities, or concomitant use of QT-prolonging drugs. Also, hypersensitivity reactions including anaphylaxis have been reported.
| Serious Effects |
Hypersensitivity to degarelix or any componentPregnancy (Category X)Severe hepatic impairment (Child-Pugh C)
| Precautions | QT prolongation and ventricular arrhythmias (especially with hypokalemia or bradycardia), Hypersensitivity reactions (urticaria, angioedema, anaphylaxis), Tumor flare reaction (transient worsening of symptoms due to initial testosterone surge) - less common with degarelix compared to GnRH agonists, Loss of bone mineral density with long-term use, Injection site reactions (pain, erythema, nodule, necrosis), Increased hepatic enzymes (transient and usually asymptomatic), Hyperglycemia and increased risk of diabetes (monitor blood glucose), Cardiovascular risks (myocardial infarction, stroke) in patients with pre-existing conditions |
| Food/Dietary | No significant food interactions. Avoid grapefruit juice if also taking certain antiarrhythmics or other QT-prolonging drugs. Maintain adequate calcium and vitamin D intake if at risk for bone loss. |
| Clinical Pearls | FIRMAGON (degarelix) is a GnRH antagonist indicated for advanced prostate cancer. It does not cause testosterone flare like GnRH agonists. Monitor serum calcium in patients with bone metastases due to risk of hypercalcemia. Injection site reactions are common; rotate sites and apply warm compresses. Use with caution in patients with congenital long QT syndrome or those on Class IA/III antiarrhythmics. |
| Patient Advice | This medication is given as an injection under the skin, usually every month. · It may cause injection site reactions like redness, swelling, or pain; applying a warm compress can help. · You may experience hot flashes, decreased libido, or erectile dysfunction. · Report any signs of allergic reaction (rash, itching, difficulty breathing) or unusual bleeding/bruising. · Regular blood tests are needed to monitor response and side effects. |
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