Firmagon Information
Firmagon (Degarelix)
Firmagon (Degarelix) Indications And Usage
Firmagon (Degarelix) is a GnRH receptor antagonist indicated for treatment of patients with advanced prostate cancer.
Firmagon (Degarelix) Dosage And Administration
Firmagon (Degarelix) is for subcutaneous administration only and is not to be administered intravenously.
Dosing information:
Firmagon (Degarelix) is administered as a subcutaneous injection in the abdominal region. 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 (Degarelix) is supplied as a powder to be reconstituted with Sterile Water for Injection, USP (WFI). The reconstitution procedure needs to be carefully followed. Administration of other concentrations is not recommended. See Instructions for Proper Use.
NOTE:
The Treatment Initiation pack contains 2 vials of Firmagon (Degarelix) 120 mg that must be prepared for 2 subcutaneous injections. Hence, the instructions here below need to be repeated a second time.
Prepare Firmagon (Degarelix) 120 mg for reconstitution by gathering the following:
The Treatment Maintenance pack contains 1 vial of Firmagon (Degarelix) 80 mg that must be prepared for subcutaneous injection.
Prepare Firmagon (Degarelix) 80 mg for reconstitution by gathering the following:
Firmagon (Degarelix) Dosage Forms And Strengths
Powder for injection 120 mg:
One vial of Firmagon (Degarelix) 120 mg contains 120 mg of degarelix. Each vial is to be reconstituted with 3 mL of Sterile Water for Injection. 3 mL is withdrawn to deliver 120 mg degarelix at a concentration of 40 mg/mL. One starting dose comprises 240 mg given as two 3 mL injections of 120 mg each.
Powder for injection 80 mg:
One vial of Firmagon (Degarelix) 80 mg contains 80 mg of degarelix. Each vial is to be reconstituted with 4.2 mL of Sterile Water for Injection. 4 mL is withdrawn to deliver 80 mg degarelix at a concentration of 20 mg/mL. One maintenance dose comprises 80 mg given as one 4 mL injection.
Firmagon (Degarelix) Contraindications
Firmagon (Degarelix) is contraindicated in patients with known hypersensitivity to degarelix or to any of the product components.
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/m 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 a mg/m 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 (Degarelix) Warnings And Precautions
Pregnancy Category X
Long-term androgen deprivation therapy prolongs the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in patients taking Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications.
In the randomized, active-controlled trial comparing Firmagon (Degarelix) to leuprolide, periodic electrocardiograms were performed. Seven patients, three (
Firmagon (Degarelix) 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 (Degarelix) 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 (Degarelix) 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 (Degarelix) was studied in an active-controlled trial (N = 610) in which patients with prostate cancer were randomized to receive Firmagon (Degarelix) (subcutaneous) or leuprolide (intramuscular) monthly for 12 months. Adverse reactions reported in 5% of patients or more are shown in Table 1.
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 (
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 (Degarelix) by the investigator:
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.
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 (Degarelix) for 1 year. There is no indication that the efficacy or safety of Firmagon (Degarelix) treatment is affected by antibody formation.
Firmagon (Degarelix) 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 . Therefore, clinically significant CYP450 pharmacokinetic drug-drug interactions are unlikely.
Firmagon (Degarelix) Use In Specific Populations
Category X
Women who are or may become pregnant should not take Firmagon (Degarelix) . 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/m 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/m 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/m 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/m basis), there was an increase in the number of minor skeletal abnormalities and variants.
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
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.
Firmagon (Degarelix) Overdosage
There have been no reports of overdose with Firmagon (Degarelix) . In the case of overdose, however, discontinue Firmagon (Degarelix) , treat the patient symptomatically, and institute supportive measures.
As with all prescription drugs, this medicine should be kept out of the reach of children.
SEE Firmagon (Degarelix) PATIENT COUNSELING INFORMATION
Firmagon (Degarelix) Description
Firmagon (Degarelix) is a sterile lyophilized powder for injection containing degarelix (as the acetate) and mannitol. Degarelix is a synthetic linear decapeptide amide containing seven unnatural amino acids, five of which are D-amino acids. The acetate salt of degarelix is a white to off-white amorphous powder of low density as obtained after lyophilization.
The chemical name of degarelix is D-Alaninamide, N-acetyl-3-(2-naphthalenyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridinyl)-D-alanyl-L-seryl-4-[[[(4S)-hexahydro-2,6-dioxo-4-pyrimidinyl]carbonyl]amino]-L phenylalanyl-4-[(aminocarbonyl)amino]-D-phenylalanyl-L leucyl-N6–(1-methylethyl)-L-lysyl-L-prolyl. It has an empirical formula of CHNOCl and a molecular weight of 1632.3 Da.
Degarelix has the following structural formula:
Firmagon (Degarelix) delivers degarelix acetate, equivalent to 120 mg of degarelix for the starting dose, and 80 mg of degarelix for the maintenance dose. The 80 mg vial contains 200 mg mannitol and the 120 mg vial contains 150 mg mannitol.
Firmagon (Degarelix) Clinical Pharmacology
A single dose of 240 mg Firmagon (Degarelix) causes a decrease in the plasma concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and subsequently testosterone.
Firmagon (Degarelix) is effective in achieving and maintaining testosterone suppression below the castration level of 50 ng/dL.
Firmagon (Degarelix) forms a depot upon subcutaneous administration, from which degarelix is released to the circulation. Following administration of Firmagon (Degarelix) 240 mg at a product concentration of 40 mg/mL, the mean C was 26.2 ng/mL (coefficient of variation, CV 83%) and the mean AUC was 1054 ng•day/mL (CV 35%). Typically C occurred within 2 days after subcutaneous administration. In prostate cancer patients at a product concentration of 40 mg/mL, the pharmacokinetics of degarelix were linear over a dose range of 120 to 240 mg. The pharmacokinetic behavior of the drug is strongly influenced by its concentration in the injection solution.
Distribution
The distribution volume of degarelix after intravenous (> 1 L/kg) or subcutaneous administration (> 1000L) indicates that degarelix is distributed throughout total body water. plasma protein binding of degarelix is estimated to be approximately 90%.
Metabolism
Degarelix is subject to peptide hydrolysis during the passage of the hepato-biliary system and is mainly excreted as peptide fragments in the feces. No quantitatively significant metabolites were detected in plasma samples after subcutaneous administration. studies have shown that degarelix is not a substrate, inducer or inhibitor of the CYP450 or p-glycoprotein transporter systems.
Excretion
Following subcutaneous administration of 240 mg Firmagon (Degarelix) at a concentration of 40 mg/mL to prostate cancer patients, degarelix is eliminated in a biphasic fashion, with a median terminal half-life of approximately 53 days. The long half-life after subcutaneous administration is a consequence of a very slow release of degarelix from the Firmagon (Degarelix) depot formed at the injection site(s). Approximately 20-30% of a given dose of degarelix was renally excreted, suggesting that approximately 70-80% is excreted via the hepato-biliary system in humans. Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9 L/hr.
Effect of Age, Weight and Race
There was no effect of age, weight, or race on the degarelix pharmacokinetic parameters or testosterone concentration.
Firmagon (Degarelix) Clinical Studies
The safety and efficacy of Firmagon (Degarelix) were evaluated in an open-label, multi-center, randomized, parallel-group study in patients with prostate cancer. A total of 620 patients were randomized to receive one of two Firmagon (Degarelix) dosing regimens or leuprolide for one year:
Serum levels of testosterone were measured at screening, on Day 0, 1, 3, 7, 14, and 28 in the first month, and then monthly until the end of the study.
The clinical trial population (n=610) across all treatment arms had an overall median age of approximately 73 (range 50 to 98). The ethnic/racial distribution was 84% white, 6% black, and 10% others. Disease stage was distributed approximately as follows: 20% metastatic, 29% locally advanced (T3/T4 Nx M0 or N1 M0), 31% localized (T1 or T2 N0 M0), and 20% classified as other (including patients whose disease metastatic status could not be determined definitively - or patients with PSA relapse after primary curative therapy). In addition, the median testosterone baseline value across treatment arms was approximately 400 ng/dL.
The primary objective was to demonstrate that Firmagon (Degarelix) is effective with respect to achieving and maintaining testosterone suppression to castration levels (T ≤ 50 ng/dL), during 12 months treatment. The results are shown in Table 2.
Percentage changes in testosterone from baseline to Day 28 (median with interquartile ranges) are shown in Figure 2 and the percentages of patients who attained the medical castration of testosterone ≤ 50 ng/dL are summarized in Table 3.
Firmagon (Degarelix) How Supplied-storage And Handling
Firmagon (Degarelix) is available as:
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
Caution should be exercised in handling and preparing the solution of Firmagon (Degarelix) . Several guidelines on proper handling and disposal of anticancer drugs have been published. To minimize the risk of dermal exposure, always wear impervious gloves when handling Firmagon (Degarelix) . If Firmagon (Degarelix) solution contacts the skin, immediately wash the skin thoroughly with soap and water. If Firmagon (Degarelix) contacts mucous membranes, the membranes should be flushed immediately and thoroughly with water .
Firmagon (Degarelix) Patient Counseling Information
(See FDA-approved Patient Labeling 17.2)
Firmagon (Degarelix) (FIRM-uh-gahn)
(degarelix for injection)
Read this patient information leaflet before you start taking Firmagon (Degarelix) and each time you get a refill.There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is Firmagon (Degarelix) ?
Firmagon (Degarelix) is a prescription medicine used in the treatment of advanced prostate cancer.
It is not known if Firmagon (Degarelix) is safe or effective in children.
Who should not use Firmagon (Degarelix) ?
Firmagon (Degarelix) should not be given to:
Talk to your healthcare provider before getting Firmagon (Degarelix) if you have any of these conditions.
Tell your healthcare provider about all the medicines you take
Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I receive Firmagon (Degarelix) ?
What are the possible side effects of Firmagon (Degarelix) ?
The common side effects include:
These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of Firmagon (Degarelix) .
This patient information leaflet summarizes the most important information about Firmagon (Degarelix) . If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Firmagon (Degarelix) that is written for health professionals.
For more information, go to or call 1-888-FERRING (1-888-337-7464).
What are the ingredients in Firmagon (Degarelix) ?
Inactive ingredient: mannitol
Manufactured for:
Ferring Pharmaceuticals Inc., Parsippany, NJ 07054
By: Rentschler Biotechnologie GmbH, Germany
6415-02
2/09
Firmagon (Degarelix) Package Label - Mg Carton
NDC 5556-8301-1
Ferring Pharmaceuticals
Firmagon (Degarelix) 80 mg
(degarelix for injection)
Rx only
For single use subcutaneous injection only
Treatment Maintenance (28 days)
Firmagon (Degarelix) Package Label - Mg Carton
NDC 55566-8401-01
Ferring Pharmaceuticals
Firmagon (Degarelix) 240mg
(degarelix for injection)
*240 mg dose administered from two vials each containing 120 mg
For single use subcutaneous injection only
Treatment Initiation
Firmagon (Degarelix) Package Label - Mg Vial Label
2008051452
NDC 55566-8301-0
Rx only
Firmagon (Degarelix) 80 mg
(degarelix for injection)
For subcutaneous injection only. Discard unused portion.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Manufactured for: Ferring Pharmaceuticals Inc.,
Parsippany, NJ 07054
By: Rentschler Biotechnologie GmbH, Germany
6411-02
Ferring Pharmaceuticals
Lot No:
Exp:
Firmagon (Degarelix) Package Label - Mg Vial Label
2008051451
NDC 55566-8401-0
Rx only
Firmagon (Degarelix) 120 mg
(degarelix for injection)
For subcutaneous injection only. Discard unused portion.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Manufactured for: Ferring Pharmaceuticals Inc.,
Parsippany, NJ 07054
By: Rentschler Biotechnologie GmbH, Germany
6413-02
Ferring Pharmaceuticals
Lot No:
Exp:
