Usage
Ganirelix is prescribed for the prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH) as part of assisted reproductive technology (ART) procedures, such as in-vitro fertilization (IVF). It belongs to the pharmacological classification of gonadotropin-releasing hormone (GnRH) antagonists. Ganirelix works by competitively blocking the GnRH receptors in the pituitary gland, thus suppressing the release of gonadotropins, particularly LH, which prevents premature ovulation before the follicles reach optimal maturity for retrieval.
Alternate Names
Generic Name: Ganirelix Acetate
Brand Names: Antagon, Fyremadel, Orgalutran, Ganirelix Gedeon Richter
How It Works
Pharmacodynamics: Ganirelix acts as a competitive GnRH receptor antagonist. By binding to these receptors in the pituitary gland, it inhibits the release of gonadotropins (LH and FSH). This prevents premature LH surges that could trigger ovulation before the developing follicles are mature enough for retrieval during assisted reproductive procedures.
Pharmacokinetics:
- Absorption: Ganirelix is administered subcutaneously, exhibiting rapid absorption. Peak serum concentrations are reached approximately 1-2 hours post-injection.
- Metabolism and Elimination: The metabolic pathways of ganirelix are not fully elucidated. It’s primarily eliminated through renal excretion, with a small portion being metabolized and eliminated hepatically.
Mode of Action: Ganirelix competes with endogenous GnRH for binding to GnRH receptors on gonadotroph cells in the anterior pituitary gland. By occupying these receptors, ganirelix prevents GnRH from stimulating the release of LH and, to a lesser extent, FSH.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Ganirelix specifically targets and antagonizes GnRH receptors. It doesn’t involve enzyme inhibition or neurotransmitter modulation in its primary mechanism of action.
Dosage
Standard Dosage
Adults:
The standard dosage is 250 mcg administered subcutaneously once daily, initiated during the mid-to-late follicular phase of the menstrual cycle (typically day 7-8, but potentially starting as early as day 2 or 3 or as late as day 12 or 13, depending on when follicle stimulating hormone (FSH) therapy was initiated) . Treatment continues until the day of human chorionic gonadotropin (hCG) administration, which triggers final follicle maturation and ovulation.
Children:
Ganirelix is not indicated for use in the pediatric population. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Specific dose adjustments are not typically required. However, clinical experience in this population is limited.
- Patients with Renal Impairment: Dose adjustments may be necessary depending on the degree of renal impairment.
- Patients with Hepatic Dysfunction: Dose modification may be necessary.
- Patients with Comorbid Conditions: No specific dose adjustments are outlined for comorbid conditions like diabetes or cardiovascular disease. However, careful monitoring is advised.
Clinical Use Cases
The clinical use of ganirelix is primarily limited to controlled ovarian hyperstimulation in the context of assisted reproductive technologies. It is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Side Effects
Common Side Effects:
- Injection site reactions (redness, pain, swelling, itching)
- Headache
- Nausea
- Abdominal pain
- Pelvic pain (similar to menstrual cramps)
- Vaginal bleeding
Rare but Serious Side Effects:
- Severe allergic reactions (anaphylaxis, angioedema, urticaria)
- Ovarian hyperstimulation syndrome (OHSS)
Long-Term Effects:
No specific long-term adverse effects have been identified with the short-term use of ganirelix in controlled ovarian stimulation protocols.
Adverse Drug Reactions (ADR):
Clinically significant ADRs primarily include severe allergic reactions and OHSS, requiring immediate medical attention.
Contraindications
- Known or suspected pregnancy
- Hypersensitivity to ganirelix, GnRH, or GnRH analogs
- Hypersensitivity to latex (some formulations contain latex in the needle shield)
- Moderate to severe renal or hepatic impairment
Drug Interactions
No clinically significant drug interactions have been consistently reported with ganirelix. However, because ganirelix can suppress pituitary gonadotropins, dose adjustments of exogenous gonadotropins (like FSH) may be necessary when used concurrently during COH.
Pregnancy and Breastfeeding
Pregnancy: Ganirelix is contraindicated in pregnancy (Pregnancy Category X). It may cause fetal harm and should not be used during pregnancy or if pregnancy is suspected.
Breastfeeding: Ganirelix should not be used during breastfeeding. It is unknown if it is excreted in human milk.
Drug Profile Summary
- Mechanism of Action: GnRH antagonist, suppresses pituitary LH and FSH release.
- Side Effects: Injection site reactions, headache, nausea, abdominal/pelvic pain, vaginal bleeding. Serious side effects: allergic reactions, OHSS.
- Contraindications: Pregnancy, hypersensitivity to ganirelix/GnRH analogs/latex, moderate-severe renal/hepatic impairment.
- Drug Interactions: Potential for altered exogenous gonadotropin dosing requirements.
- Pregnancy & Breastfeeding: Contraindicated in both.
- Dosage: 250 mcg SC daily during mid-to-late follicular phase of COH.
- Monitoring Parameters: Follicular development (ultrasound), serum estradiol (E2), LH levels.
Popular Combinations
Ganirelix is commonly used in combination with follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation. FSH stimulates follicular growth, while ganirelix prevents premature LH surges. hCG is administered when follicles reach the desired size.
Precautions
- General Precautions: Screen for allergies, especially to latex. Evaluate renal and hepatic function. Exclude pregnancy before starting treatment.
- Specific Populations: Contraindicated in pregnancy and breastfeeding. Use with caution in patients with active allergic conditions. Limited data available for elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ganirelix?
A: The standard dosage is 250 mcg subcutaneously once daily during the mid-to-late follicular phase of controlled ovarian hyperstimulation, starting on day 2, 3, or 7-8 of the cycle and continuing until the day of hCG administration.
Q2: How is Ganirelix administered?
A: Ganirelix is administered via subcutaneous injection.
Q3: What is the primary mechanism of action of Ganirelix?
A: Ganirelix competitively binds to GnRH receptors in the pituitary, preventing the release of LH and FSH, thus preventing premature ovulation.
Q4: What are the common side effects of Ganirelix?
A: Common side effects include injection site reactions, headache, nausea, abdominal pain, and pelvic pain.
Q5: Can Ganirelix be used during pregnancy?
A: No, Ganirelix is contraindicated during pregnancy. It is categorized as Pregnancy Category X and can potentially cause fetal harm.
Q6: What are the serious side effects to watch out for with Ganirelix?
A: Serious side effects include severe allergic reactions (anaphylaxis, angioedema, urticaria) and ovarian hyperstimulation syndrome (OHSS). Seek immediate medical attention if these occur.
Q7: Are there any drug interactions with Ganirelix?
A: While no specific drug interactions are consistently reported, dose adjustments of exogenous gonadotropins may be required due to Ganirelix’s suppression of pituitary gonadotropins.
Q8: What precautions should be taken before administering Ganirelix?
A: Screen patients for allergies (especially to latex), assess renal and hepatic function, and exclude pregnancy before initiating Ganirelix treatment.
Q9: How should Ganirelix be stored?
A: Ganirelix should be stored at room temperature, protected from direct light and heat.
Q10: Can Ganirelix be used in patients with renal impairment?
A: Ganirelix should be used with caution in patients with renal impairment. Dose adjustments may be necessary depending on the severity of the impairment.
