Ganirelix

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.

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.

Ganirelix is available in the form of injectable solutions.

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:-

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.

The adverse reactions related to ganirelix can be categorized as

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 Category X (FDA): When pregnant, avoid using. The risks outweigh the potential benefits. There are safer alternatives available.

It is contraindicated for pregnant women.

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.

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.

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.

As per the FDA, Ganirelix is not intended for use in this population.

As per the FDA, Ganirelix is not intended for subjects aged 65 and over.

Mild impairment: No dosage adjustment is required.

Moderate to Severe renal impairment: Contraindicated

Hepatic impairment: Contraindicated

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.

Upon administration, ganirelix exhibits rapid absorption, with a high bioavailability of 91.1%, achieving peak plasma concentration within 1.1 hours.

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.

Ganirelix undergoes hepatic metabolism facilitated by enzymatic hydrolysis, forming two primary metabolites, namely 1-4 and 1-6 peptide derivatives.

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.