Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2276
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Ganirelix Acetate (Injection, Solution)
|
| dailymed-instance:dosage |
After initiating
FSH therapy on Day 2 or 3 of the cycle, Ganirelix Acetate Injection 250��g may be administered
subcutaneously once daily during the mid to late portion of the
follicular phase. By taking advantage of endogenous pituitary FSH
secretion, the requirement for exogenously administered FSH may be
reduced. Treatment with Ganirelix Acetate should be continued daily
until the day of hCG administration. When a sufficient number of
follicles of adequate size are present, as assessed by ultrasound, final
maturation of follicles is induced by administering hCG. The
administration of hCG should be withheld in cases where the ovaries are
abnormally enlarged on the last day of FSH therapy to reduce the chance
of developing OHSS (Ovarian Hyperstimulation Syndrome).<br/>Directions for
Using Ganirelix Acetate Injection:
|
| dailymed-instance:descripti... |
Ganirelix Acetate
Injection is a synthetic decapeptide with high antagonistic activity
against naturally occurring gonadotropin-releasing hormone (GnRH).
Ganirelix Acetate is derived from native GnRH with substitutions of
amino acids at positions 1, 2, 3, 6, 8, and 10 to form the following
molecular formula of the peptide:
N-acetyl-3-(2-naphthyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridyl)-D-alanyl-L-seryl-L-tyrosyl-N,N-diethyl-D-homoarginyl-L-leucyl-N,N-diethyl-L-homoarginyl-L-prolyl-D-alanylamide
acetate. The molecular weight for Ganirelix Acetate is 1570.4 as an
anhydrous free base. The structural formula is as follows: Ganirelix Acetate Ganirelix Acetate
Injection is supplied as a colorless, sterile, ready-to-use, aqueous
solution intended for SUBCUTANEOUS administration only. Each sterile,
prefilled syringe contains 250��g/0.5 mL of Ganirelix Acetate, 0.1 mg glacial acetic acid,
23.5 mg mannitol, and water for injection adjusted to pH 5.0 with acetic
acid, NF and/or sodium hydroxide, NF.
|
| dailymed-instance:clinicalP... |
The pulsatile
release of GnRH stimulates the synthesis and secretion of luteinizing
hormone (LH) and follicle-stimulating hormone (FSH). The frequency of LH
pulses in the mid and late follicular phase is approximately 1 pulse per
hour. These pulses can be detected as transient rises in serum LH. At
midcycle, a large increase in GnRH release results in an LH surge. The
midcycle LH surge initiates several physiologic actions including:
ovulation, resumption of meiosis in the oocyte, and luteinization.
Luteinization results in a rise in serum progesterone with an
accompanying decrease in estradiol levels. Ganirelix Acetate
acts by competitively blocking the GnRH receptors on the pituitary
gonadotroph and subsequent transduction pathway. It induces a rapid,
reversible suppression of gonadotropin secretion. The suppression of
pituitary LH secretion by Ganirelix Acetate is more pronounced than that
of FSH. An initial release of endogenous gonadotropins has not been
detected with Ganirelix Acetate, which is consistent with an antagonist
effect. Upon discontinuation of Ganirelix Acetate, pituitary LH and FSH
levelsare fully recovered within 48 hours.<br/>Pharmacokinetics: The
pharmacokinetic parameters of single and multiple injections of
Ganirelix Acetate Injection in healthy adult females are
summarized in Table I. Steady-state serum concentrations are
reached after 3 days of treatment. The pharmacokinetics of
Ganirelix Acetate are dose-proportional in the dose range of 125
to 500��g.<br/>Absorption: Ganirelix Acetate is rapidly absorbed following
subcutaneous injection with maximum serum concentrations
reached approximately one hour after dosing. The mean
absolute bioavailability of Ganirelix Acetate following
a single 250��g
subcutaneous injection to healthy female volunteers is
91.1%.<br/>Distribution: The
mean (SD) volume of distribution of Ganirelix Acetate in
healthy females following intravenous administration of
a single 250��g
dose is 43.7 (11.4) liters (L). In vitro protein
binding to human plasma is 81.9%.<br/>Metabolism: Following single dose intravenous administration of
radiolabeled Ganirelix Acetate to healthy female
volunteers, Ganirelix Acetate is the major compound
present in the plasma (50���70% of total radioactivity in
the plasma) up to 4 hours and urine (17.1���18.4% of
administered dose) up to 24 hours. Ganirelix Acetate is
not found in the feces. The 1���4 peptide and 1���6 peptide
of Ganirelix Acetate are the primary metabolites
observed in the feces.<br/>Excretion: On
average, 97.2% of the total radiolabeled Ganirelix
Acetate dose is recovered in the feces and urine (75.1%
and 22.1%, respectively) over 288 h following
intravenous single dose administration of 1 mg
[C]-Ganirelix Acetate. Urinary excretion is
virtually complete in 24 h, whereas fecal excretion
starts to plateau 192 h after dosing.<br/>Special Populations: The
pharmacokinetics of Ganirelix Acetate Injection have not been
determined in special populations such as geriatric, pediatric,
renally impaired and hepatically impaired patients (see
PRECAUTIONS).<br/>Drug-Drug
Interactions: Formal in vivo
or in vitro
drug-drug interaction studies have not been conducted
. Since Ganirelix Acetate
can suppress the secretion of pituitary gonadotropins,
dose adjustments of exogenous gonadotropins may be
necessary when used during controlled ovarian
hyperstimulation (COH).<br/>Clinical Studies: The
efficacy of Ganirelix Acetate Injection was established in two
adequate and well-controlled clinical studies which included
women with normal endocrine and pelvic ultrasound parameters.
The studies intended to exclude subjects with polycystic ovary
syndrome (PCOS) and subjects with low or no ovarian reserve. One
cycle of study medication was administered to each randomized
subject.For both studies, the administration of exogenous
recombinant FSH [Follistim (follitropin beta for
injection)] 150 IU daily was initiated on the morning of Day 2
or 3 of a natural menstrual cycle. Ganirelix Acetate Injection
was administered on the morning of Day 7 or 8 (Day 6 of
recombinant FSH administration). The dose of recombinant FSH
administered was adjusted according to individual responses
starting on the day of initiation of Ganirelix Acetate. Both
recombinant FSH and Ganirelix Acetate were continued daily until
at least three follicles were 17 mm or greater in diameter at
which time hCG [Pregnyl (chorionic gonadotropin for
injection, USP)] was administered. Following hCG administration,
Ganirelix Acetate and recombinant FSH administration were
discontinued. Oocyte retrieval, followed by in vitro fertilization (IVF)
or intracytoplasmatic sperm injection (ICSI), was subsequently
performed. In a
multicenter, double-blind, randomized, dose-finding study, the
safety and efficacy of Ganirelix Acetate Injection were
evaluated for the prevention of LH surges in women undergoing
COH with recombinant FSH. Ganirelix Acetate Injection doses
ranging from 62.5��g to
2000��g and recombinant
FSH were administered to 332 patients undergoing COH for IVF
(see Table II). Median serum LH on the day of hCG
administration decreased with increasing doses of Ganirelix
Acetate. Median serum E(17b-estradiol) on the day of hCG
administration was 1475, 1110, and 1160 pg/mL for the 62.5, 125,
and 250��g doses,
respectively. Lower peak serum Elevels of 823, 703,
and 441 pg/mL were seen at higher doses of Ganirelix Acetate
500, 1000, and 2000��g,
respectively. The highest pregnancy and implantation rates were
achieved with the 250��g
dose of Ganirelix Acetate Injection as summarized in Table II. Transient
LH rises alone were not deleterious to achieving pregnancy with
Ganirelix Acetate at doses of 125��g (3/6 subjects) and 250��g (1/1 subjects). In
addition, none of the subjects with LH rises���10 mIU/mL had
premature luteinization indicated by a serum progesterone above
2 ng/mL. A
multicenter, open-label, randomized study was conducted to
assess the efficacy and safety of Ganirelix Acetate Injection in
women undergoing COH. Follicular phase treatment with Ganirelix
Acetate 250��g was
studied using a luteal phase GnRH agonist as a reference
treatment. A total of 463 subjects were treated with Ganirelix
Acetate by subcutaneous injection once daily starting on Day 6
of recombinant FSH treatment. Recombinant FSH was maintained at
150 IU for the first 5 days of ovarian stimulation and was then
adjusted by the investigator on the sixth day of gonadotropin
use according to individual responses. The results for the
Ganirelix Acetate arm are summarized in Table III. Some centers were limited to the transfer of���2 embryos
based on local practice standards The mean number of days of Ganirelix Acetate treatment
was 5.4 (2���14). There was no incidence of drug-related allergic
reactions within the adequate and well-controlled clinical
studies.<br/>LH Surges: The
midcycle LH surge initiates several physiologic actions
including: ovulation, resumption of meiosis in the
oocyte, and luteinization. In 463 subjects administered
Ganirelix Acetate Injection 250��g, a premature LH
surge prior to hCG administration, (LH rise���10 mIU/mL
with a significant rise in serum progesterone>2
ng/mL, or a significant decline in serum estradiol)
occurred in less than 1% of subjects.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Ganirelix Acetate
Injection is contraindicated under the following conditions: ���Known
hypersensitivity to Ganirelix Acetate or to any of its components. ���Known
hypersensitivity to GnRH or any other GnRH analog. ���Known or suspected pregnancy .
|
| dailymed-instance:supply |
Ganirelix Acetate
Injection is supplied in: Disposable,
sterile, prefilled 1 mL glass syringes containing 250��g/0.5 mL of Ganirelix Acetate. Each
Ganirelix Acetate sterile, prefilled syringe is affixed with a 27 gauge
x/-inch needle and is blister-packed. Single
syringe NDC
0052-0301-51<br/>Storage: Store at
25��C (77��F); excursions permitted to 15���30��C (59���86��F) [see USP
Controlled Room Temperature]. Protect from light. Rx only Manufactured for Organon USA Inc.Roseland, NJ 07068by
Vetter Pharma-Fertigung GmbH&Co. KGRavensburg,
Germanyand packaged by Organon (Ireland) Ltd.Swords
Co.,Dublin, Ireland10/05
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
General: Caution is
advised in patients with hypersensitivity to GnRH. These
patients should be carefully monitored after the first
injection. Anaphylactic reactions or ganirelix antibody
formation have not been reported in the clinical trials for
Ganirelix Acetate Injection. The
packaging of this product contains natural rubber latex which
may cause allergic reactions.<br/>Information for
Patients: Prior to
therapy with Ganirelix Acetate Injection, patients should be
informed of the duration of treatment and monitoring procedures
that will be required. The risk of possible adverse reactions
should be discussed (see ADVERSE
REACTIONS). Ganirelix
Acetate should not be prescribed if the patient is
pregnant.<br/>Laboratory Tests: A
neutrophil count���8.3 ( x 10/L) was noted in 11.9%
(up to 16.8 x 10/L) of all subjects treated within
the adequate and well-controlled clinical trials. In addition,
downward shifts within the Ganirelix Acetate Injection group
were observed for hematocrit and total bilirubin. The clinical
significance of these findings was not determined.<br/>Drug Interactions: No formal
drug-drug interaction studies have been performed.<br/>Carcinogenesis and
Mutagenesis and Impairment of Fertility: Long-term
toxicity studies in animals have not been performed with
Ganirelix Acetate Injection to evaluate the carcinogenic
potential of the drug. Ganirelix Acetate did not induce a
mutagenic response in the Ames test (S. typhimurium and E. coli) or produce
chromosomal aberrations in in
vitro assay using Chinese Hamster Ovary
cells.<br/>Pregnancy:<br/>Pregnancy Category
X: Ganirelix Acetate Injection is contraindicated in
pregnant women. When administered from Day 7 to near
term to pregnant rats and rabbits at doses up to 10 and
30��g/day
(approximately 0.4 to 3.2 times the human dose based on
body surface area), Ganirelix Acetate increased the
incidence of litter resorption. There was no increase in
fetal abnormalities. No treatment-related changes in
fertility, physical, or behavioral characteristics were
observed in the offspring of female rats treated with
Ganirelix Acetate during pregnancy and lactation. The
effects on fetal resorption are logical consequences of
the alteration in hormonal levels brought about by the
antigonadotrophic properties of this drug and could
result in fetal loss in humans. Therefore, this drug
should not be used in pregnant women .<br/>Nursing Mothers: Ganirelix
Acetate Injection should not be used by lactating women. It is
not known whether this drug is excreted in human
milk.<br/>Geriatric Use: Clinical
studies with Ganirelix Acetate Injection did not include a
sufficient number of subjects aged 65 and over.
|
| dailymed-instance:overdosag... |
There have been no
reports of overdosage with Ganirelix Acetate Injection in
humans.
|
| dailymed-instance:genericMe... |
Ganirelix Acetate
|
| dailymed-instance:fullName |
Ganirelix Acetate (Injection, Solution)
|
| dailymed-instance:adverseRe... |
The safety of
Ganirelix Acetate Injection was evaluated in two randomized,
parallel-group, multicenter controlled clinical studies. Treatment
duration for Ganirelix Acetate ranged from 1 to 14 days. Table IV
represents adverse events (AEs) from first day of Ganirelix Acetate
administration until confirmation of pregnancy by ultrasound at an
incidence of���1% in Ganirelix Acetate-treated subjects without regard
to causality. Congenital Anomalies Ongoing clinical
follow-up studies of 283 newborns of women administered Ganirelix
Acetate Injection were reviewed. There were three neonates with major
congenital anomalies and 18 neonates with minor congenital anomalies.
The major congenital anomalies were: hydrocephalus/meningocele,
omphalocele, andBeckwith-Wiedemann Syndrome. The minor congenital
anomalies were: nevus, skin tags, sacral sinus, hemangioma,
torticollis/asymmetric skull, talipes, supernumerary digit finger, hip
subluxation, torticollis/high palate, occiput/abnormal hand crease,
hernia umbilicalis, hernia inguinalis, hydrocele, undescended testis,
and hydronephrosis. The causal relationship between these congenital
anomalies and Ganirelix Acetate is unknown. Multiple factors, genetic
and others (including, but not limited to ICSI, IVF,gonadotropins,
progesterone) may confound ART (Assisted Reproductive Technology)
procedures.
|
| dailymed-instance:warning |
Ganirelix Acetate
Injection should be prescribed by physicians who are experienced in
infertility treatment. Before starting treatment with Ganirelix Acetate,
pregnancy must be excluded. Safe use of Ganirelix Acetate during
pregnancy has not been established .
|
| dailymed-instance:indicatio... |
Ganirelix Acetate
Injection is indicated for the inhibition of premature LH surges in
women undergoing controlled ovarian hyperstimulation.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Ganirelix Acetate
|