Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 09 August 2018

Indication(s)

1 INDICATIONS AND USAGE FIRMAGON is a GnRH receptor antagonist indicated for treatment of patients with advanced prostate cancer. FIRMAGON is a GnRH receptor antagonist indicated for treatment of patients with advanced prostate cancer. (1)

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Advisory information

contraindications
4 CONTRAINDICATIONS FIRMAGON is contraindicated in patients with known hypersensitivity to degarelix or to any of the product components. [see Warnings and Precautions (5.2)]. Degarelix is contraindicated in women who are or may become pregnant. Degarelix can cause fetal harm when administered to a pregnant woman. Degarelix given to rabbits during organogenesis at doses that were 0.02% of the clinical loading dose (240 mg) on a mg/m2 basis caused embryo/fetal lethality and abortion. When degarelix was given to female rats during organogenesis, at doses that were just 0.036% of the clinical loading dose on an mg/m2 basis, there was an increase post implantation loss and a decrease in the number of live fetuses. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. FIRMAGON is contraindicated in: Patients with previous hypersensitivity reactions to degarelix (4) Pregnancy Category X. Fetal harm can occur when administered to pregnant women (4)
Adverse reactions
6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 1325 patients with prostate cancer received FIRMAGON either as a monthly treatment (60-160 mg) or as a single dose (up to 320 mg). A total of 1032 patients (78%) were treated for at least 6 months and 853 patients (64%) were treated for one year or more. The most commonly observed adverse reactions during FIRMAGON therapy included injection site reactions (e.g., pain, erythema, swelling or induration), hot flashes, increased weight, fatigue, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT). The majority of the adverse reactions were Grade 1 or 2, with Grade 3/4 adverse reaction incidences of 1% or less. FIRMAGON was studied in an active-controlled trial (N = 610) in which patients with prostate cancer were randomized to receive FIRMAGON (subcutaneous) or leuprolide (intramuscular) monthly for 12 months. Adverse reactions reported in 5% of patients or more are shown in Table 1. Table 1. Adverse Reactions Reported in > 5% of Patients in an Active Controlled Study FIRMAGON 240/160 mg (subcutaneous) N = 202 FIRMAGON 240/80 mg (subcutaneous) N = 207 Leuprolide 7.5 mg (intramuscular) N = 201 Percentage of subjects with adverse events 83% 79% 78% Body as a whole Injection site adverse events 44% 35% <1% Weight increase 11% 9% 12% Fatigue 6% 3% 6% Chills 4% 5% 0% Cardiovascular system Hot flash 26% 26% 21% Hypertension 7% 6% 4% Musculoskeletal system Back pain 6% 6% 8% Arthralgia 4% 5% 9% Urogenital system Urinary tract infection 2% 5% 9% Digestive system Increases in Transaminases and GGT 10% 10% 5% Constipation 3% 5% 5% The most frequently reported adverse reactions at the injection sites were pain (28%), erythema (17%), swelling (6%), induration (4%) and nodule (3%). These adverse reactions were mostly transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (<1%). Grade 3 injection site reactions occurred in 2% or less of patients receiving degarelix. Hepatic laboratory abnormalities were primarily Grade 1 or 2 and were generally reversible. Grade 3 hepatic laboratory abnormalities occurred in less than 1% of patients. In 1-5% of patients the following adverse reactions, not already listed, were considered related to FIRMAGON by the investigator: Body as a whole: Asthenia, fever, night sweats; Digestive system: Nausea; Nervous system: Dizziness, headache, insomnia. The following adverse reactions, not already listed, were reported to be drug-related by the investigator in ≥1% of patients: erectile dysfunction, gynecomastia, hyperhidrosis, testicular atrophy, and diarrhea. The safety of FIRMAGON administered monthly was evaluated further in an extension study in 385 patients who completed the above active-controlled trial. Of the 385 patients, 251 patients continued treatment with FIRMAGON and 135 patients crossed over treatment from leuprolide to FIRMAGON. The median treatment duration on the extension study was approximately 43 months (range 1 to 58 months). The most common adverse reactions reported in ≥10% of the patients were injection site reactions (e.g., pain, erythema, swelling, induration or inflammation), pyrexia, hot flush, weight loss or gain, fatigue, increases in serum levels of hepatic transaminases and GGT. One percent of patients had injection site infections including abscess. Hepatic laboratory abnormalities in the extension study included the following: Grade 1/2 elevations in hepatic transaminases occurred in 47% of patients and Grade 3 elevations occurred in 1% of patients. The most commonly observed adverse reactions (≥10%) during FIRMAGON therapy included injection site reactions (e.g., pain, erythema, swelling or induration), hot flashes, increased weight, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT) (6) To report SUSPECTED ADVERSE REACTIONS, contact Ferring at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Changes in bone density: Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist. It can be anticipated that long periods of medical castration in men will result in decreased bone density. Anti-degarelix antibody development has been observed in 10% of patients after treatment with FIRMAGON for 1 year. There is no indication that the efficacy or safety of FIRMAGON treatment is affected by antibody formation.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION FIRMAGON is for subcutaneous administration only Treatment is started with a dose of 240 mg given as two injections of 120 mg each (2.1) The starting dose is followed by maintenance doses of 80 mg administered as a single injection every 28 days (2.1) 2.1 Dosing information FIRMAGON is administered as a subcutaneous injection in the abdominal region only. Starting dose Maintenance dose – Administration every 28 days 240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL 80 mg given as one subcutaneous injection at a concentration of 20 mg/mL The first maintenance dose should be given 28 days after the starting dose. 2.2 Reconstitution and Administration Instructions FIRMAGON® is to be administered by a healthcare professional only. Before administering FIRMAGON read the Instructions for reconstitution and administration carefully. As with other drugs administered by subcutaneous injection, the injection site should vary periodically. Injections should be given in areas of the abdomen that will not be exposed to pressure, e.g., not close to waistband or belt nor close to the ribs. FIRMAGON is supplied as a powder to be reconstituted with Sterile Water for Injection, USP (WFI). The instruction for reconstitution needs to be carefully followed. Administration of other concentrations is not recommended. Read the complete instructions before performing the injection. NOTE: FIRMAGON is for subcutaneous administration to the abdominal region only. Reconstituted drug must be administered within one hour after addition of Sterile Water for Injection, USP. Do not shake the vials. Follow aseptic technique. FIRMAGON 240 mg Starting Dose Kit contains: 2 vials containing the 120 mg FIRMAGON® powder (a) 2 syringes containing Sterile Water for Injection, USP (b) 2 vial adapters (c) 2 injection needles (d) 2 plunger rods (e) FIRMAGON 80 mg Maintenance Dose Kit contains: 1 vial containing the 80 mg FIRMAGON® powder (f) 1 syringe containing Sterile Water for Injection, USP (g) 1 vial adapter (h) 1 injection needle (i) 1 plunger rod (j) In addition the healthcare professional will need: gloves (k) alcohol pads (l) a clean, flat surface (m) to work on, like a table a sharps disposal container (n) for throwing away your used needles and syringes. See "Disposing used needles and syringes" at the end of these instructions. The drug product must be prepared using the following instructions: NOTE: The mixing process must be repeated for the two injections of the Starting Dose prior to injecting the product into the patient's abdomen. Step 1: Attaching the vial adaptor to the vial Thoroughly wash your hands using soap and water and put on a pair of clean gloves. Place all the supplies required on a clean surface. Check that there is powder in the FIRMAGON® vial and that the Sterile Water, USP is clear and free from particles. IMPORTANT: DO NOT USE if there is no powder in the vial or the Sterile Water, USP is discolored. Uncap the vial containing the FIRMAGON® powder (o). Wipe the vial rubber stopper with an alcohol pad. IMPORTANT: Do not touch the top of the vial after wiping. Peel off the seal from the vial adaptor cover. IMPORTANT: Do not touch the vial adapter. Firmly press the vial adaptor (p) onto the vial containing the FIRMAGON® powder until the adaptor snaps into place. Pull the vial adaptor cover off the vial. Step 2: Assembling the syringe Insert the plunger rod (q) into the prefilled syringe containing Sterile Water, USP (r) and screw the plunger rod clockwise to tighten. IMPORTANT: Do not pull the back stopper (flange) (s) off the syringe. NOTE: You will only feel light resistance screwing the plunger rod in position. Step 3: Transferring sterile water, USP from the syringe to the vial Unscrew the gray syringe plug (t) attached to the Luer lock adaptor on the syringe. IMPORTANT: Do not pull off the Luer lock adaptor (u). Carefully twist the prefilled syringe containing sterile water, USP onto the vial adapter on the FIRMAGON® powder vial, until it is tight. IMPORTANT: Be careful not to over twist the syringe. Press the plunger slowly to transfer all the sterile water, USP from the syringe to the FIRMAGON® powder vial. Step 4: Preparing the reconstituted injection With the syringe still attached to the vial adaptor, swirl gently until the liquid is clear with no powder or visible particles. IMPORTANT: Do not shake the vial as this will cause bubbles. Reconstitute just prior to administration. NOTE: If the powder adheres to the side of the vial, tilt the vial slightly. A ring of small air bubbles on the surface of the liquid is acceptable. Reconstitution time can take up to 15 min but usually takes a few minutes. Step 5: Transferring the liquid to the syringe Turn the vial completely upside down and pull down the plunger to withdraw all of the reconstituted liquid from the vial to the syringe. Tap the syringe gently with your fingers to raise air bubbles in the syringe tip. Press the plunger to the line marked on the syringe to expel all air bubbles. Step 6: Preparing the syringe for injection Holding the vial adaptor detach the syringe from the vial by unscrewing the syringe from the vial adaptor. NOTE: Reconstitute just prior to administration. While holding the syringe with the tip pointing up, screw the injection needle (v) clockwise (right) onto the syringe. Step 7: Preparing the patient Select one of the four available injection sites on the abdomen. IMPORTANT: Do not inject in areas where the patient will be exposed to pressure, such as area around the belt of the waistband or close to the ribs. Vary the injection site periodically during treatment to minimize discomfort to the patient. Clean the injection site with an alcohol pad. Step 8: Performing the injection Move the needle shield (w) away from the needle and carefully remove the needle cover (x). Pinch and elevate the skin of the abdomen. Insert the needle into the skin at a 45 degree angle all the way to the hub. Do not inject into a vein or muscle. Gently pull back the plunger to check if blood is aspirated. IMPORTANT: If blood appears in the syringe, the product should not be injected. Discontinue the injection and discard the syringe and the needle (reconstitute a new dose for the patient). Perform a slow, deep subcutaneous injection over 30 seconds. Remove the needle and then release the skin. IMPORTANT: Do not rub the injection site after retracting the needle. Step 9: Locking the needle into the shield Position the needle shield approximately 45 degrees to a flat surface. Press down with a firm, quick motion until a distinct, audible "click" is heard. Visually confirm that the needle is fully engaged under the lock (y). IMPORTANT: Syringe is for single use only. Do not reuse the syringe and needle. Step 10: Advising the patient Instruct the patient not to rub or scratch the injection site. Inform that some patients may feel a lump at the injection site and experience redness, soreness and discomfort for a few days after the injection. Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Disposing used needles and syringes Put used alcohol swabs, needles and syringes in an FDA-cleared sharps disposal container right away after use. Do not throw away loose needles and syringes in the trash. For more information about safe sharps disposal, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
Use in special populations
8 USE IN SPECIFIC POPULATIONS There is no need to adjust the dose for the elderly or in patients with mild or moderate liver or kidney function impairment. Patients with severe liver or kidney dysfunction have not been studied and caution is therefore warranted (8) 8.1 Pregnancy Category X [see Contraindications (4) and Warnings and Precautions (5.1)] Women who are or may become pregnant should not take FIRMAGON. When degarelix was given to rabbits during early organogenesis at doses of 0.002 mg/kg/day (about 0.02% of the clinical loading dose on a mg/m2 basis), there was an increase in early post-implantation loss. Degarelix given to rabbits during mid and late organogenesis at doses of 0.006 mg/kg/day (about 0.05% of the clinical loading dose on a mg/m2 basis) caused embryo/fetal lethality and abortion. When degarelix was given to female rats during early organogenesis, at doses of 0.0045 mg/kg/day (about 0.036% of the clinical loading dose on a mg/m2 basis), there was an increase in early post-implantation loss. When degarelix was given to female rats during mid and late organogenesis, at doses of 0.045 mg/kg/day (about 0.36% of the clinical loading dose on a mg/m2 basis), there was an increase in the number of minor skeletal abnormalities and variants. 8.3 Nursing Mothers FIRMAGON is not indicated for use in women and is contraindicated in women who are or who may become pregnant. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from degarelix, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of subjects in clinical studies of FIRMAGON, 82% were age 65 and over, while 42% were age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Renal Impairment No pharmacokinetic studies in renally impaired patients have been conducted. At least 20-30% of a given dose of degarelix is excreted unchanged in the urine. A population pharmacokinetic analysis of data from the randomized study demonstrated that there is no significant effect of mild renal impairment [creatinine clearance (CrCL) 50-80 mL/min] on either the degarelix concentration or testosterone concentration. Data on patients with moderate or severe renal impairment is limited and therefore degarelix should be used with caution in patients with CrCL < 50 mL/min. 8.7 Hepatic Impairment Patients with hepatic impairment were excluded from the randomized trial. A single dose of 1 mg degarelix administered as an intravenous infusion over 1 hour was studied in 16 non-prostate cancer patients with either mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Compared to non-prostate cancer patients with normal liver function, the exposure of degarelix decreased by 10% and 18% in patients with mild and moderate hepatic impairment, respectively. Therefore, dose adjustment is not necessary in patients with mild or moderate hepatic impairment. However, since hepatic impairment can lower degarelix exposure, it is recommended that in patients with hepatic impairment testosterone concentrations should be monitored on a monthly basis until medical castration is achieved. Once medical castration is achieved, an every-other-month testosterone monitoring approach could be considered. Patients with severe hepatic dysfunction have not been studied and caution is therefore warranted in this group.
Pregnancy and lactation
8.3 Nursing Mothers FIRMAGON is not indicated for use in women and is contraindicated in women who are or who may become pregnant. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from degarelix, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Interactions

7 DRUG INTERACTIONS No drug-drug interaction studies were conducted. Degarelix is not a substrate for the human CYP450 system. Degarelix is not an inducer or inhibitor of the CYP450 system in vitro. Therefore, clinically significant CYP450 pharmacokinetic drug-drug interactions are unlikely. Clinically significant CYP450 pharmacokinetic drug-drug interactions are unlikely (7)

More information

Category Value
Authorisation number NDA022201
Orphan designation No
Product NDC 55566-8403,55566-8303
Date Last Revised 15-05-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 828751
Storage and handling Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Discard all components safely in an appropriate biohazard container.
Marketing authorisation holder Ferring Pharmaceuticals Inc.