Indications and Usage for Firmagon
Firmagon is a GnRH receptor
antagonist indicated for treatment of patients with advanced prostate cancer.
Firmagon Dosage and AdministrationDosing information
Firmagon is administered as a
subcutaneous injection in the abdominal region only.
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Starting
dose
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Maintenance
dose – Administration every 28 days
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240 mg given as
two subcutaneous injections of 120 mg at a concentration of 40 mg/mL
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80 mg given as
one subcutaneous injection at a concentration of 20 mg/mL
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The first maintenance dose
should be given 28 days after the starting dose.
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.
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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)
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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)
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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.
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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.
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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.
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· 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.
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· 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.
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· Pull
the vial adaptor cover off the vial.
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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.
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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).
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· 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.
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· Press
the plunger slowly to transfer all the sterile water, USP from the syringe to
the Firmagon® powder vial.
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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.
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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.
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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.
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· While
holding the syringe with the tip pointing up, screw the injection needle (v)
clockwise (right) onto the syringe.
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Step 7: Preparing the patient
· Select
one of the four available injection sites on the abdomen.
IMPORTANT:
o 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.
o Vary the injection site periodically during
treatment to minimize discomfort to the patient.
· Clean
the injection site with an alcohol pad.
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Step 8: Performing the injection
· Move
the needle shield (w) away from the needle and carefully remove the needle
cover (x).
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· 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.
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· Remove the needle and then release the skin.
IMPORTANT: Do not rub
the injection site after retracting the needle.
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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.
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· 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.
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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.
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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.
Dosage Forms and Strengths
Starting dose
One starting dose comprises
240 mg given as two 3 mL injections of 120 mg each.
Powder for injection 120 mg:
One vial of Firmagon 120 mg
contains 120 mg degarelix. Each vial is to be reconstituted with a prefilled
syringe containing 3 mL of Sterile Water for Injection. 3 mL is withdrawn to
deliver 120 mg degarelix at a concentration of 40 mg/mL.
Maintenance dose
One maintenance dose comprises
80 mg given as one 4 mL injection.
Powder for injection 80 mg:
One vial of Firmagon 80 mg
contains 80 mg degarelix. Each vial is to be reconstituted with a prefilled
syringe containing 4.2 mL of Sterile Water for Injection. 4 mL is withdrawn to
deliver 80 mg degarelix at a concentration of 20 mg/mL.
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.
Warnings and PrecautionsUse in Pregnancy
Pregnancy
Category X
Women who are or may become
pregnant should not take Firmagon [see Contraindications
(4) and Use in
Specific Populations (8.1)].
Hypersensitivity Reactions
Hypersensitivity reactions,
including anaphylaxis, urticaria and angioedema, have been reported
post-marketing with Firmagon. In case of a serious hypersensitivity reaction,
discontinue Firmagon immediately if the injection has not been completed, and
manage as clinically indicated. Patients with a known history of serious
hypersensitivity reactions to Firmagon should not be re-challenged with
Firmagon.
Effect on QT/QTc Interval
Androgen deprivation therapy may prolong
the QT interval. Providers should consider whether the benefits of androgen
deprivation therapy outweigh the potential risks in patients with congenital
long QT syndrome, congestive heart failure, frequent electrolyte abnormalities,
and in patients taking drugs known to prolong the QT interval. Electrolyte
abnormalities should be corrected. Consider periodic monitoring of
electrocardiograms and electrolytes.
In the randomized,
active-controlled trial comparing Firmagon to leuprolide, periodic
electro-cardiograms were performed. Seven patients, three (<1%) in the
pooled degarelix group and four (2%) patients in the leuprolide 7.5 mg group,
had a QTcF ≥ 500 msec. From baseline to end of study, the median change for
Firmagon was 12.3 msec and for leuprolide was 16.7 msec.
Laboratory Testing
Therapy with Firmagon results
in suppression of the pituitary gonadal system. Results of diagnostic tests of
the pituitary gonadotropic and gonadal functions conducted during and after
Firmagon may be affected. The therapeutic effect of Firmagon should be
monitored by measuring serum concentrations of prostate-specific antigen (PSA)
periodically. If PSA increases, serum concentrations of testosterone should be
measured.
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
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Firmagon
240/160 mg
(subcutaneous)
N = 202
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Firmagon
240/80 mg
(subcutaneous)
N = 207
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Leuprolide
7.5 mg
(intramuscular)
N = 201
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Percentage of
subjects with adverse events
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83%
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79%
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78%
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Body as a whole
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Injection site
adverse events
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44%
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35%
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<1%
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Weight increase
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11%
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9%
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12%
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Fatigue
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6%
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3%
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6%
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Chills
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4%
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5%
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0%
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Cardiovascular system
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Hot flash
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26%
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26%
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21%
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Hypertension
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7%
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6%
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4%
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Musculoskeletal system
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Back pain
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6%
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6%
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8%
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Arthralgia
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4%
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5%
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9%
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Urogenital system
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Urinary tract
infection
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2%
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5%
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9%
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Digestive system
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Increases in
Transaminases and GGT
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10%
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10%
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5%
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Constipation
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3%
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5%
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5%
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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.
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.
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.
USE IN SPECIFIC POPULATIONSPregnancy
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.
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.
Pediatric Use
Safety and effectiveness in
pediatric patients have not been established.
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.
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.
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.
Overdosage
There have been no reports of
overdose with Firmagon. In the case of overdose, however, discontinue Firmagon,
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
PATIENT COUNSELING INFORMATION
Firmagon Description
Firmagon 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 C82H103N18O16Cl and a molecular weight of 1632.3 Da.
Degarelix has the following
structural formula:
Firmagon 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 - Clinical PharmacologyMechanism of Action
Degarelix is a GnRH receptor
antagonist. It binds reversibly to the pituitary GnRH receptors, thereby
reducing the release of gonadotropins and consequently testosterone.
Pharmacodynamics
A single dose of 240 mg
Firmagon causes a decrease in the plasma concentrations of luteinizing hormone
(LH) and follicle stimulating hormone (FSH), and subsequently testosterone.
Firmagon is effective in
achieving and maintaining testosterone suppression below the castration level
of 50 ng/dL.
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Figure 1: Plasma Testosterone Levels from
Day 0 to 364 for Degarelix 240 mg/80 mg (Median with Interquartile Ranges)
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Pharmacokinetics
Absorption
Firmagon forms a depot upon
subcutaneous administration, from which degarelix is released to the
circulation. Following administration of Firmagon 240 mg at a product
concentration of 40 mg/mL, the mean Cmax was 26.2 ng/mL (coefficient of
variation, CV 83%) and the mean AUC was 1054 ng∙day/mL (CV 35%). Typically Cmax
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. In vitro 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. In vitro 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 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 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.
Nonclinical ToxicologyCarcinogenesis, Mutagenesis,
Impairment of Fertility
Degarelix was administered
subcutaneously to rats every 2 weeks for 2 years at doses of 2, 10 and 25 mg/kg
(about 9, 45 and 120% of the recommended human loading dose on a mg/m2 basis). Long term
treatment with degarelix at 25 mg/kg caused an increase in the combined
incidence of benign hemangiomas plus malignant hemangiosarcomas in females.
Degarelix was administered
subcutaneously to mice every 2 weeks for 2 years at doses of 2, 10 and 50 mg/kg
(about 5, 22 and 120% of the recommended human loading dose (240 mg) on a mg/m2 basis). There was no
statistically significant increase in tumor incidence associated with this
treatment.
Degarelix did not cause
genetic damage in standard in vitro assays
(bacterial mutation, human lymphocyte chromosome aberration) nor in in vivo rodent bone marrow micronucleus tests.
Single degarelix doses of ≥ 1
mg/kg (about 5% of the clinical loading dose on a mg/m2 basis) caused reversible
infertility in male rats. Single doses of ≥ 0.1 mg/kg (about 0.5% of the
clinical loading dose on a mg/m2 basis) caused a decrease in fertility in female rats.
Clinical Studies
The safety and efficacy of
Firmagon 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 dosing regimens or leuprolide
for one year:
1. Firmagon at a starting dose of 240 mg (40 mg/mL) followed by
monthly doses of 160 mg (40 mg/mL) subcutaneously,
2. Firmagon at a starting dose of 240 mg (40 mg/mL) followed by monthly
doses of 80 mg (20 mg/mL) subcutaneously,
3. leuprolide 7.5 mg intramuscularly monthly.
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 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.
Table 2: Medical Castration Rates (Testosterone ≤ 50 ng/dL) from Day
28 to Day 364
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Firmagon
240/160 mg
N=202
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Firmagon
240/80 mg
N=207
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Leuprolide
7.5 mg
N=201
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|
*
Kaplan Meier estimates within group
|
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No. of
Responders
|
199
|
202
|
194
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Castration Rate
(95% CIs)*
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98.3%
(94.8; 99.4)
|
97.2%
(93.5; 98.8)
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96.4%
(92.5; 98.2)
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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.
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Figure 2: Percentage Change in
Testosterone from Baseline by Treatment Group until Day 28 (Median with
Interquartile Ranges)
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Table 3: Percentage of Patients Attaining Testosterone ≤ 50 ng/dL
within the First 28 Days
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Firmagon
240/160 mg
N=202
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Firmagon
240/80 mg
N=207
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Leuprolide
7.5 mg
N=201
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Day 1
|
44%
|
52%
|
0%
|
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Day 3
|
96%
|
96%
|
0%
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Day 7
|
99%
|
99%
|
1%
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Day 14
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99%
|
99%
|
18%
|
|
Day 28
|
99%
|
100%
|
100%
|
In the clinical trial, PSA
levels were monitored as a secondary endpoint. PSA levels were lowered by 64%
two weeks after administration of Firmagon, 85% after one month, 95% after
three months, and remained suppressed throughout the one year of treatment. These
PSA results should be interpreted with caution because of the heterogeneity of
the patient population studied. No evidence has shown that the rapidity of PSA
decline is related to a clinical benefit.
How Supplied/Storage and Handling
Firmagon is available as:
NDC 55566-8403-1, Starting dose – One carton
contains:
Two vials each with 120 mg powder for injection
Two prefilled syringes containing 3 mL of sterile water for injection, USP
Two vial adapters
Two administration needlesNDC 55566-8303-1, Maintenance dose – One carton
contains:
One vial with 80 mg powder for injection
One prefilled syringe containing 4.2 mL of sterile water for injection,
USP
One vial adapter
One administration needle
Store at 25°C (77°F);
excursions permitted to 15-30°C (59-86°F).
Discard all components safely
in an appropriate biohazard container.
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Patient Information).
-
Patients should be informed of
the possible side effects of androgen deprivation therapy, including hot
flashes, flushing of the skin, increased weight, decreased sex drive, and
difficulties with erectile function. Possible side effects related to therapy
with Firmagon include redness, swelling, and itching at the injection site;
these are usually mild, self limiting, and decrease within three days.
MANUFACTURED FOR:
FERRING
PHARMACEUTICALS INC., PARSIPPANY, NJ 07054
Manufactured in Germany
2009054575
Rev. 07/2016
Patient Information
Firmagon
(FIRM-uh-gahn)
(degarelix for injection)
What is Firmagon?
Firmagon
is a prescription medicine used in the treatment of advanced prostate cancer.
It is
not known if Firmagon is safe or effective in children.
Who should not receive Firmagon?
Do not
receive Firmagon if you are:
·
allergic to degarelix or any
ingredient in Firmagon. See the end of this leaflet for a complete list of
ingredients in Firmagon.
·
a female who is pregnant or
may become pregnant. Firmagon can harm your unborn baby.
Talk
to your healthcare provider before receiving Firmagon if you have any of these
conditions.
Before receiving Firmagon, tell your healthcare provider about
all your medical conditions, including if you:
·
have any heart problems
including a condition called long QT syndrome.
·
have problems with blood
levels such as sodium, potassium, calcium, and magnesium
·
have kidney or liver problems
·
are breastfeeding or plan to
breastfeed. It is not known if Firmagon passes into your breast milk. You and
your healthcare provider should decide if you will receive Firmagon or
breastfeed. You should not do both.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
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 will I receive Firmagon?
You
will receive an injection of Firmagon from your healthcare provider.
·
The injection site will always
be in the stomach (abdominal area). The injection site will change within the
stomach area each time you receive a dose of Firmagon.
·
Two injections are given as a
first dose. The following monthly doses are one injection.
·
Do not rub or scratch the
injection site. Make sure your injection site is free of any pressure from
belts, waistbands or other types of clothing.
·
Always set up an appointment
for your next injection.
What are the possible side effects of Firmagon?
Firmagon can cause serious side effects, including:
· Serious
allergic reactions. Get medical help right
away if you get any of these symptoms:
|
o trouble
breathing or wheezing
o severe
itching
|
o swelling
of your face, lips, mouth, or tongue
|
· Disorder
of the heart's electrical activity. Your
healthcare provider may do tests during treatment with Firmagon to check your
heart for a condition called long QT syndrome.
The common side effects of Firmagon include:
|
· injection
site pain, redness, and swelling
· hot
flashes
|
· weight
gain
· increase
in some liver enzymes
|
Other
side effects include decreased sex drive and erectile function problems.
Tell
your healthcare provider if you have any side effect that bothers you or that
does not go away.
These
are not all the possible side effects.
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.
Medicines
are sometimes prescribed for conditions that are not mentioned in a Patient
Information leaflet. Do not use Firmagon for a condition for which it was not
prescribed. Do not give Firmagon to other people, even if they have the same
symptoms that you have. It may harm them.
You
can ask your pharmacist or healthcare provider for information about Firmagon
that is written for health professionals.
What are the ingredients in Firmagon?
Active
ingredient: degarelix (as acetate)
Inactive
ingredient: mannitol
MANUFACTURED FOR:
FERRING
PHARMACEUTICALS INC., PARSIPPANY, NJ 07054
Manufactured in Germany
For
more information, go to www.Firmagon.com or call -1-888-337-7464.
This
Patient Information has been approved by the U.S. Food and Drug Adminstration.
2009054575
Rev. 07/2016
PRINCIPAL DISPLAY PANEL - 240 mg Kit Carton
NDC 55566-8403-1
FERRING
PHARMACEUTICALS
Firmagon® 240mg*
(degarelix for injection)
* 240
mg dose administered from
two vials each containing 120 mg
For single use subcutaneous injection only
Discard unused portion
Kit contents:
2
vials each with 120 mg powder
for injection
2
syringes with sterile water
for injection, USP
for reconstitution/administration
2
vial adapters
2
administration needles
Initiation Dose
Rx only
PRINCIPAL DISPLAY PANEL - 80 mg Kit Carton
NDC 55566-8303-1
FERRING
PHARMACEUTICALS
Firmagon® 80mg
(degarelix for injection)
For single use subcutaneous injection only
Discard unused portion
Kit
contents:
1
vial with 80 mg powder for injection
1
syringe with sterile water for injection, USP
for reconstitution/administration
1
vial adapter
1
administration needle
Maintenance Dose (28 Days)
Rx only
|
Firmagon degarelix kit
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:55566-8403
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:55566-8403-1
|
1 KIT in 1
CARTON
|
|
|
|
Quantity of
Parts
|
|
Part #
|
Package
Quantity
|
Total
Product Quantity
|
|
|
|
Part 1
|
2 VIAL, GLASS
|
6 mL
|
|
|
|
Part 2
|
2 SYRINGE
|
6 mL
|
|
|
|
|
Part
1 of 2
|
|
Firmagon degarelix
powder, metered
|
|
|
Product Information
|
|
|
|
|
|
|
Route of
Administration
|
SUBCUTANEOUS
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Degarelix (Degarelix)
|
Degarelix
|
40 mg
in 1 mL
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Mannitol
|
50 mg
in 1 mL
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
|
|
Shape
|
|
Size
|
|
|
Flavor
|
|
Imprint Code
|
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
|
3 mL in 1 VIAL,
GLASS
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA022201
|
03/02/2009
|
|
|
|
Part
2 of 2
|
|
STERILE WATER water
injection, solution
|
|
|
Product
Information
|
|
|
|
|
|
|
Route of
Administration
|
SUBCUTANEOUS
|
DEA Schedule
|
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Water
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
|
3 mL in 1
SYRINGE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA022201
|
03/02/2009
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA022201
|
03/02/2009
|
|
|
|
Firmagon degarelix kit
|
|
Product
Information
|
|
Product Type
|
HUMAN PRESCRIPTION
DRUG LABEL
|
Item Code
(Source)
|
NDC:55566-8303
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:55566-8303-1
|
1 KIT in 1
CARTON
|
|
|
|
Quantity of
Parts
|
|
Part #
|
Package
Quantity
|
Total
Product Quantity
|
|
|
|
Part 1
|
2 VIAL, GLASS
|
8 mL
|
|
|
|
Part 2
|
1 SYRINGE
|
4.2 mL
|
|
|
|
|
Part
1 of 2
|
|
Firmagon degarelix
powder, metered
|
|
|
Product
Information
|
|
|
|
|
|
|
Route of
Administration
|
SUBCUTANEOUS
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Degarelix (Degarelix)
|
Degarelix
|
20 mg
in 1 mL
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Mannitol
|
50 mg
in 1 mL
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
|
|
Shape
|
|
Size
|
|
|
Flavor
|
|
Imprint Code
|
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
|
4 mL in 1 VIAL,
GLASS
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA022201
|
03/02/2009
|
|
|
|
Part
2 of 2
|
|
STERILE WATER water
injection, solution
|
|
|
Product
Information
|
|
|
|
|
|
|
Route of
Administration
|
SUBCUTANEOUS
|
DEA Schedule
|
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Water
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
|
4.2 mL in 1
SYRINGE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application Number
or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA022201
|
03/02/2009
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA022201
|
03/02/2009
|
|
|
|
Labeler - Ferring Pharmaceuticals Inc. (103722955)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Rentschler
Biotechnologie GmbH
|
|
332952766
|
MANUFACTURE(55566-8403,
55566-8303), PACK(55566-8403, 55566-8303), ANALYSIS(55566-8403, 55566-8303)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Ferring
International Center SA
|
|
481210362
|
PACK(55566-8403,
55566-8303)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Ferring Gmbh -
Kiel
|
|
328609615
|
MANUFACTURE(55566-8403,
55566-8303), ANALYSIS(55566-8403, 55566-8303), PACK(55566-8403, 55566-8303)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
PolyPeptide
Laboratories
|
|
356580779
|
API
MANUFACTURE(55566-8403, 55566-8303)
|
Revised: 08/2016
Ferring Pharmaceuticals Inc.
