- Home
- Medical news & Guidelines
- Anesthesiology
- Cardiology and CTVS
- Critical Care
- Dentistry
- Dermatology
- Diabetes and Endocrinology
- ENT
- Gastroenterology
- Medicine
- Nephrology
- Neurology
- Obstretics-Gynaecology
- Oncology
- Ophthalmology
- Orthopaedics
- Pediatrics-Neonatology
- Psychiatry
- Pulmonology
- Radiology
- Surgery
- Urology
- Laboratory Medicine
- Diet
- Nursing
- Paramedical
- Physiotherapy
- Health news
- Fact Check
- Bone Health Fact Check
- Brain Health Fact Check
- Cancer Related Fact Check
- Child Care Fact Check
- Dental and oral health fact check
- Diabetes and metabolic health fact check
- Diet and Nutrition Fact Check
- Eye and ENT Care Fact Check
- Fitness fact check
- Gut health fact check
- Heart health fact check
- Kidney health fact check
- Medical education fact check
- Men's health fact check
- Respiratory fact check
- Skin and hair care fact check
- Vaccine and Immunization fact check
- Women's health fact check
- AYUSH
- State News
- Andaman and Nicobar Islands
- Andhra Pradesh
- Arunachal Pradesh
- Assam
- Bihar
- Chandigarh
- Chattisgarh
- Dadra and Nagar Haveli
- Daman and Diu
- Delhi
- Goa
- Gujarat
- Haryana
- Himachal Pradesh
- Jammu & Kashmir
- Jharkhand
- Karnataka
- Kerala
- Ladakh
- Lakshadweep
- Madhya Pradesh
- Maharashtra
- Manipur
- Meghalaya
- Mizoram
- Nagaland
- Odisha
- Puducherry
- Punjab
- Rajasthan
- Sikkim
- Tamil Nadu
- Telangana
- Tripura
- Uttar Pradesh
- Uttrakhand
- West Bengal
- Medical Education
- Industry
Ganirelix
Indications, Uses, Dosage, Drugs Interactions, Side effects
Ganirelix
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Gonadotropin-releasing hormone (GnRH) antagonists, Therapy Class:
Synthetic hormone, Approved Countries
The United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Ganirelix is a synthetic hormone belonging to the pharmacological class of Gonadotropin-releasing hormone (GnRH) antagonists.
The FDA has approved for the treatment of female infertility, specifically for the prevention of premature ovulation.
Ganirelix rapidly absorbs (91.1% bioavailability), distributes widely, undergoes liver metabolism, and is predominantly eliminated via faeces and urine.
The most common side effects of ganirelix include injection site reaction (redness, itching, and irritation), nausea and vomiting.
Ganirelix is available in the form of injectable solutions (prefilled syringes).
The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Ganirelix is a synthetic hormone belonging to the pharmacological class of Gonadotropin-releasing hormone (GnRH) antagonists.
The synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary is mediated by gonadotropin-releasing hormone (GnRH), a releasing hormone generated from the hypothalamus. Ovulation, the oocyte's restart of meiosis, and luteinization are among the physiological processes that are triggered by a substantial rise in GnRH release during midcycle, which causes an LH surge. Luteinization causes a reduction in estradiol levels and an increase in progesterone in the bloodstream.
During assisted reproductive technology (ART), controlled ovarian hyperstimulation (COH) is used in conjunction with other procedures such as in vitro fertilization (IVF). COH is advantageous since it makes it possible to schedule IVF procedures. Because prematurely increased LH levels can impede appropriate multiple follicular maturation and result in an undesired increase in progesterone levels, suppressing early surges of LH is crucial during this intervention. By competitively inhibiting the GnRH receptors on the pituitary gonadotroph and related transduction pathways, Ganirelix seeks to reduce premature LH surges. Gonadotropin secretion is quickly and easily suppressed by Ganirelix. Ganirelix suppresses pituitary LH results more strongly than it does FSH. Ganirelix does not appear to cause an initial release of endogenous gonadotropins, which is consistent with an antagonist effect.
Peak plasma concentration reaches 14.8 ng/mL for single doses and 11.2 ng/mL for multiple doses.
The peak plasma time is approximately 1.1 hours.
The area under the curve (AUC) measures 96 ng·hr/mL for single doses and 77.1 ng·hr/mL for multiple doses.
Ganirelix is available in the form of injectable solutions (prefilled syringes).
Injectable solutions: Ganirelix injection is administered only subcutaneously. For proper use, adhere to the doctor's recommendations.
As the physician recommends, take the medication orally once daily; it can be taken with or without food as directed.
- It inhibits premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation.
- It suppresses the action of gonadotropin-releasing hormone (GnRH), preventing early ovulation and enhancing the likelihood of a successful pregnancy.
In Female infertility
Ganirelix helps in treating premature LH surges in women undergoing controlled ovarian hyperstimulation. By inhibiting gonadotropin-releasing hormone (GnRH) action, ganirelix suppresses LH, preventing early ovulation during ovarian stimulation. This aids in treating female infertility and enhancing the likelihood of successful pregnancy. Patients should not self-administer ganirelix; it requires injection by medical professionals.
It is indicated for women undergoing controlled ovarian hyperstimulation in order to prevent early LH surges during assisted reproductive methods (ART).
Parenterally: Administer ganirelix subcutaneously after thoroughly cleaning about 2 inches of skin around the needle insertion site near the abdomen's navel or upper thigh. Pinch a significant skin area between fingers and thumb, inserting the needle at a 45-90° angle to the skin surface. Proper needle placement prevents pulling back on the plunger. Upon accurate positioning, depress the plunger and dispose of the syringe following use, adhering to recommended disposal procedures and rotating injection sites to prevent tissue irritation.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Injectable solutions (prefilled syringe): 250mcg/0.5mL
Ganirelix is available in the form of injectable solutions.
Dose Adjustment in Adult Patients:
Female Infertility Treatment: 250 mcg SC qDay in the mid-to-late phase following the cycle's follicle-stimulating hormone (FSH), starting on day two or three.
Up until the day of chorionic gonadotropin administration, continue with the course of therapy.
While using ganirelix, avoid fried and processed foods. Consuming high-fat dairy, like whole milk, is advisable over low-fat options. Incorporate fibre-rich foods—whole grains, fruits, and vegetables—into your diet. Refrain from high-sugar refined carbohydrates. Limiting the intake of grapefruit juice is recommended due to possible interactions. Minimize alcohol and caffeine intake, as they exacerbate symptoms. Cease smoking and alcohol consumption for improved symptom management.
The dietary restriction should be individualized as per patient requirements.
Ganirelix may be contraindicated in the following conditions:-
- Hypersensitivity to ganirelix or any of its components.
- Known hypersensitivity to GnRH or any other GnRH analogs.
- Known or suspected pregnancy and lactation.
Warnings
Physicians with expertise in fertility treatment should be responsible for prescribing ganirelix. Before beginning Ganirelix medication, pregnancy needs to be ruled out. Safe use of ganirelix during pregnancy has not been established.
Precautions
- Hypersensitivity reaction: Women showing signs or symptoms of active allergic conditions should exercise caution when using ganirelix. Reports from post-marketing surveillance have highlighted cases of hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, potentially occurring with the initial dose. In the event of suspected hypersensitivity, discontinuing ganirelix and administering suitable treatment is recommended. Women with severe allergic conditions should avoid Ganirelix treatment due to limited clinical experience.
- Ovarian hyperstimulation syndrome (OHSS): Ovarian stimulation can cause OHSS, either during or after it. Gonadotropin stimulation carries an inherent danger, which is OHSS. OHSS should be managed symptomatically, such as rest, heparin, and intravenous infusion of electrolyte solutions or colloids.
Alcohol Warning
It is unsafe to consume alcohol.
Breast Feeding Warning
It is not recommended for use during breastfeeding.
Pregnancy Warning
It is unsafe to use during pregnancy.
Food Warning
Avoid fried foods, choose whole dairy, and limit alcohol intake.
The adverse reactions related to ganirelix can be categorized as
- Common Adverse Effects: Abdominal pain, headache, injection site reactions, nausea
- Less Common Adverse Effects: Ovarian hyperstimulation syndrome, vaginal bleeding, and pelvic pain.
- Rare Adverse Effects: Anaphylactoid reactions.
Reports on Postmarketing
Angioedema
Urticaria
Ganirelix lacks formal drug interaction studies. It is impossible to completely rule out the possibility of interactions with regularly used medications, especially those that release histamine.
The common side effects of ganirelix include:-
Headache
Nausea
Hyperstimulation of the ovaries
Pain in the abdomen
bleeding vaginally
Reactions at the injection site include redness and swelling
- Pregnancy
Pregnancy Category X (FDA): When pregnant, avoid using. The risks outweigh the potential benefits. There are safer alternatives available.
It is contraindicated for pregnant women.
Animal data
When administered to pregnant rats and rabbits from Day 7 to near term at doses up to 10 and 30 mcg per day (approximately 0.4- 3.2 times the human dose based on body surface area), ganirelix enhanced the incidence of litter resorption. Fetal abnormalities did not rise. The progeny of female rats administered ganirelix acetate during gestation and lactation did not show treatment-related alterations in terms of behavior, physical attributes, or fertility.
Ectopic pregnancy
The risk of ectopic pregnancies may be elevated in infertile women undergoing assisted reproduction, especially in vitro fertilization (IVF), because these women frequently have tubal abnormalities. It is crucial to have early ultrasound confirmation of an intrauterine pregnancy.
- Nursing Mothers
It is not recommended to be used by lactating mothers, and it is unknown if human milk contains ganirelix secreted in it. Nursing mothers should not use ganirelix because it has not been determined how it would affect lactation or the breastfed infant, as many medications are excreted in human milk.
- Pediatric Use
As per the FDA, Ganirelix is not intended for use in this population.
- Geriatric Use
As per the FDA, Ganirelix is not intended for subjects aged 65 and over.
Dose Adjustment in Kidney Impairment Patients:
Mild impairment: No dosage adjustment is required.
Moderate to Severe renal impairment: Contraindicated
Dose Adjustment in Hepatic Impairment Patients:
Hepatic impairment: Contraindicated
No human data regarding ganirelix's acute toxicity exists. Clinical trials administering single subcutaneous doses up to 12 mg displayed no systemic adverse reactions. Acute toxicity studies in rats and monkeys revealed non-specific toxic symptoms—like hypotension and bradycardia—only with intravenous ganirelix over 1 and 3 mg per kg, respectively. In case of overdose, temporarily cease ganirelix treatment.
Pharmacodynamics:
Ganirelix suppresses endogenous gonadotropins quickly, profoundly, and reversibly, which regulates the hypothalamic-pituitary-gonadal axis. During controlled ovarian stimulation, it inhibits the pituitary gland's release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Ganirelix does not elicit an initial rise in gonadotropin levels before premature LH surge inhibition, in contrast to GnRH agonists. Additionally, ganirelix does not cause flare-ups, prolonged down-regulation periods brought on by GnRH agonists, or hypo-estrogenic adverse effects.
Ganirelix therapy lasted five days on average for individuals receiving controlled ovarian stimulation. In one study, the injection of 0.25 mg ganirelix in successive doses resulted in a drop in serum LH, FSH, and estradiol (E2) baseline values by 74, 32, and 25%, respectively, following the final treatment. After the last injection, serum hormone levels recovered to their pre-treatment levels in two days.
Pharmacokinetics:
Absorption
Upon administration, ganirelix exhibits rapid absorption, with a high bioavailability of 91.1%, achieving peak plasma concentration within 1.1 hours.
Distribution
Within the body, ganirelix has a distribution volume of 43.7 L for single doses and 76.5 L for multiple doses, with approximately 81.9% binding to plasma proteins.
Metabolism
Ganirelix undergoes hepatic metabolism facilitated by enzymatic hydrolysis, forming two primary metabolites, namely 1-4 and 1-6 peptide derivatives.
Elimination
Following metabolism, the drug is primarily eliminated through faeces, accounting for roughly 75% of the administered dose within 288 hours, while approximately 22% is excreted via urine within 24 hours. The elimination half-life of ganirelix stands at 12.8 hours for single doses and slightly extends to 16.2 hours for multiple doses.
- Han EJ, Lyu SW, Kwak IP, Kwon H, Choi DH, Kim JY, Park HM, Kim JW, Chang EM, Lee HJ, Kim MK, Lee HN, Kim JY, Park S, Lee WS. Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study. J Obstet Gynaecol. 2022 Aug;42(6):2197-2202. doi: 10.1080/01443615.2022.2036955. Epub 2022 Mar 7. PMID: 35254199.
- Fluker M, Grifo J, Leader A, Levy M, Meldrum D, Muasher SJ, Rinehart J, Rosenwaks Z, Scott RT Jr, Schoolcraft W, Shapiro DB; North American Ganirelix Study Group. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril. 2001 Jan;75(1):38-45. doi: 10.1016/s0015-0282(00)01638-1. PMID: 11163814.
- Choudhary RA, Vora PH, Darade KK, Pandey S, Ganla KN. A Prospective Randomised Comparative Clinical Trial Study of Luteal PhaseLetrozole versus Ganirelix Acetate Administration to Prevent Severity of Early Onset OHSS in ARTs. Int J Fertil Steril. 2021 Oct;15(4):263-268. doi: 10.22074/IJFS.2021.139562.1042. Epub 2021 Oct 16. PMID: 34913294; PMCID: PMC8530210.
- 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). The ganirelix dose-finding study group. Hum Reprod. 1998 Nov;13(11):3023-31. PMID: 9853849.
- US Food and Drug Administration (FDA) [Internet]. Maryland. USA; Package leaflet information for the user; Antagona (ganirelix acetate)
- Therapeutic Goods Administration (TGA): Department of Health [Internet]. Governmet of Australia; Package leaflet information for the user; Orgalutran® (ganirelix acetate)
- https://www.ema.europa.eu/en/documents/product-information/ganirelix
- https://pubmed.ncbi.nlm.nih.gov/10718102/
Dr. Chumbeni E Lotha has completed her Bachelor of Pharmacy from RIPANS, Mizoram and Doctor of Pharmacy from SGRRU,Dehradun. She can be reached at editorial@medicaldialogues.in
Dr JUHI SINGLA has completed her MBBS from Era’s Lucknow Medical college and done MD pharmacology from SGT UNIVERSITY Gurgaon. She can be contacted at editorial@medicaldialogues.in. Contact no. 011-43720751
Published on: 29 Nov 2023 11:39 AM GMT