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Ganirelix Acetate

Class: Gonadotropin-releasing Hormone Antagonists
VA Class: HS400
Chemical Name: N - Acetyl - 3 - (2 - naphthalenyl) - d - alanyl - 4 - chloro - d - phenylalanyl - 3 - (3 - pyridinyl) - d - alanyl - l - seryl - l - tyrosyl - N6 - [(ethylamino)(ethylimino)methyl] - l - lysyl - l - prolyl - d - alaninamide diacetate (salt)
Molecular Formula: C80H113ClN18O13
CAS Number: 129311-55-3

Introduction

Gonadotropin-releasing hormone (GnRH) antagonist.1 2 3 4 5

Uses for Ganirelix Acetate

Female Infertility

Used as a component of infertility regimens (recombinant FSH, ganirelix, and human chorionic gonadotropin [hCG]) to inhibit premature LH surges in women undergoing controlled ovarian hyperstimulation (COH).1 2 3

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Ganirelix Acetate Dosage and Administration

General

  • Should be prescribed by clinicians experienced in infertility treatment.1

  • Prior to use of ganirelix, initiate COH therapy with FSH on the morning of day 2 or 3 of the menstrual cycle.1 Individualize dosage of FSH based on the patient’s ovarian response to allow sufficient follicular development.1

  • Initiate therapy with ganirelix on the morning of day 7 or 8 of the cycle (day 6 of FSH therapy) and continue combination therapy until sufficient follicular growth is verified (e.g., ultrasound).1 2

  • When ultrasound assessement shows sufficient follicular maturation, discontinue FSH therapy and ganirelix and administer hCG to complete final follicular maturation and induce ovulation.1 Perform oocyte retrieval, followed by in vitro fertilization or intracytoplasmic sperm injection, with subsequent attempts at implantation and pregnancy.1 2 3

  • Do not administer hCG if the ovaries show an excessive response to treatment with FSH because of an increased risk of ovarian hyperstimulation syndrome.1

Administration

Sub-Q Administration

Administer by sub-Q injection once daily during the mid- to late-follicular phase of the menstrual cycle.1

Administer into abdomen, preferably around the umbilicus, or upper thigh; rotate injection sites.1

Dosage

Adults

Female Infertility
Sub-Q

250 mcg once daily in combination with FSH therapy; initiate on the morning of day 6 of FSH therapy.1 Continue until an an adequate follicular response to stimulation therapy is achieved; a mean duration of 5.4 days was required in clinical trials.1 (See General under Dosage and Administration.)

Cautions for Ganirelix Acetate

Contraindications

  • Known hypersensitivity to ganirelix or any ingredient in the formulation.1

  • Known hypersensitivity to GnRH or any other GnRH analog.1

  • Known or suspected pregnancy.1 6 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryolethality and fetal mortality demonstrated in animals.1 Congenital anomalies reported in women who received ganirelix during pregnancy.1

Exclude pregnancy prior to initiation of therapy.1

Sensitivity Reactions

GnRH Sensitivity

Anaphylactic reactions or ganirelix antibody formation not reported; however, the possibility of GnRH hypersensitivity exists.1 6 Monitor carefully after initial injection.1 6

Latex Sensitivity

Packaging components contain natural rubber latex; possible latex sensitivity reaction in susceptible individuals.1

Specific Populations

Pregnancy

Category X.1 May result in fetal loss secondary to antigonadotropic properties.1 (See Contraindications and also Fetal/Neonatal Morbidity and Mortality, under Cautions.)

Lactation

Not known whether ganirelix is distributed into milk.1 Use not recommended.1

Pediatric Use

Not intended for use in pediatric patients.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patient respond differently than younger adults.1

Common Adverse Effects

Gynecologic abdominal pain,1 headache,1 ovarian hyperstimulation syndrome,1 vaginal bleeding,1 injection site reactions,1 6 nausea,1 GI abdominal pain.1

Interactions for Ganirelix Acetate

No formal drug interaction studies to date.1

Ganirelix Acetate Pharmacokinetics

Absorption

Bioavailability

Average absolute bioavailability in healthy females is 91.1%.1

Distribution

Extent

Not known whether ganirelix is distributed into milk.1

Plasma Protein Binding

81.9%.1

Elimination

Metabolism

Metabolized to the 1-4 and 1-6 peptide of ganirelix.1

Elimination Route

Excreted in the feces (75.1%) and to a lesser extent in urine (22.1%).1

Half-life

12.8–16.2 hours.1

Stability

Storage

Parenteral

Injection

25°C (may be exposed to 15–30°C); protect from light.1

Actions

  • Competitively blocks GnRH receptors on the pituitary gonadotroph and the subsequent transduction pathway,1 inducing a rapid, reversible suppression of gonadotropin (LH, FSH) secretion.1 2 4 5

  • Suppression of pituitary LH secretion is more pronounced than that of FSH.1 Associated decreases in sex hormones (e.g., estradiol, testosterone) occur.2 5

  • Suppresses the midcycle GnRH-induced surge in LH and suppresses ovulation,1 5 oocytic meiosis, and luteinization.1

  • Prevents the LH surges associated with COH therapy1 2 3 and improves implantation and pregnancy rates associated with in vitro fertilization.1 2 3

Advice to Patients

  • Importance of discussing duration of treatment and required monitoring procedures.1

  • Risk of potential adverse effects.1

  • Importance of advising women of risk of fetal harm if administered during pregnancy;1 need for pregnancy testing prior to initiation of therapy.1 Importance of women informing their clinician if they plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ganirelix Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use only

250 mcg/0.5 mL

Ganirelix Acetate Injection (in prefilled syringes)

Organon

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Organon Inc. Ganirelix acetate injection prescribing information. West Orange NJ; 2004 May.

2. The Ganirelix Dose-Finding Study Group. A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon). Hum Reprod. 1998; 13:3023-31. [PubMed 9853849]

3. Itskovitz-Eldor J, Kol S, Mannaerts B et al. First established pregnancy after controlled ovarian hyperstimulation with recombinant follicle stimulating hormone and the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462). Hum Reprod. 1998; 13:294-5. [PubMed 9557825]

4. Nelson LR, Fujimoto VY, Jaffe RB et al. Suppression of follicular phase pituitary-gonadal function by a potent new gonadotrophin-releasing hormone antagonist with reduced histamine-releasing properties (ganirelix). Fertil Steril. 1995; 63:963-9. [IDIS 347016] [PubMed 7536693]

5. Rabinovici J, Rothman P, Monroe SE et al. Endocrine effects and pharmacokinetic chracteristics of a potent new gonadotropin-releasing hormone antagonist (Ganirelix) with minimal histamine-releasing properties: studies in postmenopausal women. J Clin Endocrinol Metab. 1992; 75:1220-5. [IDIS 305364] [PubMed 1385467]

6. Organon, West Orange, NJ: Personal communication.

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