Professional Information
Ganirelix (Systemic )
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VA CLASSIFICATION
Primary: HS900
Commonly used brand name(s): Antagon.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
†Not commercially available in Canada.
Category:
Gonadatropin-releasing hormone antagonist—
Indications
Accepted
Infertility, treatment (female)—Ganirelix is indicated for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation. {01}
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Ganirelix is a synthetic decapeptide, derived from native gonadatropin-releasing hormone with substitutions of amino acids in several positions{01}.
Molecular weight—
1570.4{01}
pH
The pH of ganirelix is adjusted to 5.0 with acetic acid, NF and/or sodium hydroxide, NF{01}.
Mechanism of action/Effect:
Infertility, treatment (female)—Ganirelix competitively blocks gonadotropin–releasing hormone (GnRH) receptors on the pituitary gonadotroph and subsequent transduction pathway. Ganirelix induces a rapid, reversible suppression of gonadotropin secretion. The suppression of pituitary LH secretion by ganirelix is more pronounced than that of FSH. An initial release of endogenous gonadotropins has not been detected with ganirelix, which is consistent with an antagonist effect. Upon discontinuation of ganirelix, pituitary LH and FSH levels are fully recovered within 48 hours.{01}
Absorption:
Ganirelix is rapidly absorbed following subcutaneous injection. Mean absolute bioavailability is 91.1%{01}.
Distribution:
The mean volume of distribution in healthy females following intravenous administration of a single 250 microgram dose is 43.7 liters{01}.
Protein binding:
High (81.9%) In vitro protein binding to human plasma {01}.
Biotransformation:
Following single dose intravenous administration of radiolabeled ganirelix to healthy female volunteers, ganirelix is the major compound present in the plasma (50% to 70% of total radioactivity in the plasma) up to 4 hours and urine (17.1% to 18.4% of the administered dose) up to 24 hours. Ganirelix is not found in the feces. The 1–4 peptide and the 1–6 peptide of ganirelix are the primary metabolites observed in the feces{01}.
Half-life:
Subcutaneous (single dose): 12.8 hours{01}.
Subcutaneous (multiple dose): 16.2 hours{01}.
Time to peak concentration:
Maximum serum concentrations are reached approximately 1 hour after dosing{01}.
Elimination:
Following a single dose intravenous administration of 1 mg [14C]-ganirelix:
—Fecal 75.1%{01}
Note: Fecal excretion starts to plateau 192 hours after administration{01}.
—Renal 22.1%{01}
Note: Renal excretion is virtually complete after 24 hours{01}.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to gonadotrophin-releasing hormone (gnRH) and its analogs may be sensitive to ganirelix also{01}.
The packaging of the product contains natural rubber latex which may cause allergic reactions{01}
Carcinogenicity
Long-term studies have not been performed in animals to evaluate the carcinogenic potential of ganirelix {01}.
Mutagenicity
Ganirelix did not induce a mutagenic response in the Ames test (S. typhimurium and E. coli) or produce chromosomal aberrations in an in vitro assay using Chinese Hamster Ovary cells{01}.
Pregnancy/Reproduction
Pregnancy—
Ganirelix is not recommended during pregnancy. Studies in pregnant rats and rabbits given ganirelix at doses up to 10 and 30 mcg/day (approximately 0.4 to 3.2 times the human dose based on body surface area), have shown increased incidence of litter resorption. There was no increase in fetal abnormalities. 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{01}.
FDA Pregnancy Category X{01}.
Breast-feeding
It is not known whether ganirelix is distributed into breast milk{01}. Use of ganirelix in lactating women is not recommended.
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With physiology/laboratory test values
Neutrophil count (A neutrophil count ³ 8.3 ( × 109/L) was noted in 11.9% (up to 16.8 × 109/L) of all subjects treated within the adequate and well-controlled clinical trials{01}.)
Hematocrit
Total bilirubin (may be decreased{01}.)
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
The medication should not be used when the following medical problem exists:
» Hypersensitivity to ganirelix or to any of its component
» Hypersensitivity to gonadotropin-releasing hormone or any other GnRH analog
»
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for immediate medical attention
Incidence less frequent{01}
Fetal death
Ovarian hyperstimulation syndrome (abdominal pain, severe ; nausea and vomiting; rapid weight gain )
Those indicating need for medical attention
Incidence less frequent{01}
abdominal pain, gynecological
abdominal pain, gastrointestinal
vaginal bleeding
Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent{01}
headache
injection site reaction (redness, pain or swelling at injection site)
nausea
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ganirelix (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Hypersensitivity to gonadotropin-releasing hormones or analogs {01}
(The packaging of the product contains natural rubber latex which may cause allergic reactions){01}
Pregnancy—Use in known or suspected pregnancy is contraindicated{01}
Breast-feeding—It is not known if ganirelix is excreted in human breast milk. Ganirelix is not recommended in lactating women{01}.
Proper use of this medication
» Carefully read patient instructions provided
For patients self-administering the medication
• Proper preparation of medication; use proper technique to prevent contamination of medication, work area, and patient
• Proper administration; use proper needle and syringe
• Know proper dose to use and not using more than prescribed
• Carefully selecting and rotating injection sites as directed by physician
• Notifying physician after using last dose of ganirelix
» Proper dosing
Call physician for advice; do not double dose
» Proper storage
Precautions while using this medication
» Telling physician if allergy to natural rubber exists
» Regular visits with physician to check progress
» Importance of following physician instructions for recording basal body temperature, if requested, and timing of intercourse
» Discontinuing treatment if severe abdominal pain occurs and notifying physician of the problem
Side/adverse effects
Signs of potential side effects, including fetal death, ovarian hyperstimulation syndrome, abdominal pain (gynecological or gastrointestinal), vaginal bleeding
General Dosing Information
Patients receiving ganirelix should be under the supervision of a physician experienced in the treatment of infertility.
Since ganirelix can suppress the secretion of pituitary gonadotropins, dose adjustments of exogenous gonadotropins may be necessary when used during controlled ovarian hyperstimulation{01}
Safety considerations for handling this medication
• Use of proper technique to prevent contamination of the medication, including proper training in this technique for self-administration of this medication by patients.
• Cautious and proper disposal of syringes and unused medication.
Directions for using ganirelix acetate injection
#149; Ganirelix is supplied in a sterile, prefilled syringe and is intended for SUBCUTANEOUS administration only.
#149; Wash hands thoroughly with soap and water.
#149; The most convenient sites for SUBCUTANEOUS injection are in the abdomen around the navel or upper thigh.
#149; The injection site should be swabbed with a disinfectant to remove any surface bacteria. Clean about 2 inches around the point where the needle will be inserted and let the disinfectant dry for at least 1 minute before proceeding.
#149; Remove needle cover.
#149; Pinch up a large area of skin between the finger and thumb. Vary the injection site with each injection.
#149; The needle should be inserted at the base of the pinched-up skin at an angle of 45° to 90° to the skin surface.
#149; When the needle is correctly positioned, it will be difficult to draw back the plunger. If any blood is drawn into the syringe, the needle tip has penetrated a vein or artery. If this happens, withdraw the needle slightly and reposition the needle without removing it from the skin. Cover the injection site with a swab containing disinfectant and apply pressure; the site should stop bleeding within 1 or 2 minutes.
#149; Once the needle is correctly placed, depress the plunger slowly and steadily, so the solution is correctly injected and the skin is not damaged.
#149; Pull the syringe out quickly and apply pressure to the site with a swab containing disinfectant.
#149; Use the sterile, prefilled syringe only once and dispose of it properly.
Parenteral Dosage Forms
GANIRELIX ACETATE INJECTION
Usual Adult Dose
Infertility, treatment (female)
Subcutaneous, 250 micrograms once daily during the early to mid follicular phase following initiation of FSH therapy on Day 2 or 3 of the cycle{01}.
Note: By taking advantage of endogenous pituitary FSH secretion, the requirement for exogenously administered FSH may be reduced. Treatment with ganirelix 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 {01}.
Strength(s) usually available
U.S.—
250 mcg per 0.5 mL in a prefilled 1 mL glass syringe (Rx) [Antagon (Each sterile prefilled syringe is affixed with a 27 gauge × 1/2 inch needle) ( acetic acid, glacial 0.1 mg) (mannitol 23.5 mg) (water for injection)]
Packaging and storage:
Store at 25° C (77° F); excursions permitted to 15° C to 30° C (59° F to 86° F){01}. Protect from light{01}.
Developed: 12/07/1999
References
- Product Information: Antagon ™, ganirelix acetate. Organon Inc., West Orange, NJ, USA, June 1999.
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