Cetrorelix

Usage

Cetrorelix is prescribed to prevent premature luteinizing hormone (LH) surges in women undergoing controlled ovarian stimulation (COS) as part of assisted reproductive technology (ART) like in-vitro fertilization (IVF). It belongs to the pharmacological class of gonadotropin-releasing hormone (GnRH) antagonists. Cetrorelix competitively binds to GnRH receptors in the pituitary gland, blocking the action of endogenous GnRH, thereby reducing the release of LH and follicle-stimulating hormone (FSH). This prevents premature ovulation before the follicles are mature enough for retrieval.

Alternate Names

Cetrorelix acetate is the other name commonly used. Cetrotide is a popular brand name for cetrorelix.

How It Works

Pharmacodynamics: Cetrorelix competitively binds to GnRH receptors in the pituitary gland, thus preventing endogenous GnRH from binding and subsequently decreasing the secretion of gonadotropins (LH and FSH). Suppression of LH prevents premature ovulation during controlled ovarian stimulation.

Pharmacokinetics:

• Absorption: Following subcutaneous injection, cetrorelix is absorbed rapidly, reaching peak plasma concentrations (Cmax) in approximately 1 to 2 hours.
• Metabolism: Cetrorelix is metabolized to smaller peptides. The primary metabolites are cetrorelix (1-9), (1-7), (1-6), and (1-4). Metabolism is not dependent on the cytochrome P450 system.
• Elimination: Cetrorelix and its metabolites are excreted primarily via renal (2-4% as unchanged drug) and hepatic routes (5-10% as unchanged drug and metabolites), with a terminal half-life (t1/2) of approximately 63 hours after a single 3 mg dose, 5 hours after a single 0.25 mg dose, and around 21 hours with multiple 0.25 mg doses.

Mode of action: Cetrorelix acts as a competitive antagonist at GnRH receptors in the anterior pituitary gland. It competes with endogenous GnRH for binding sites, thereby inhibiting GnRH-mediated release of LH and, to a lesser extent, FSH.

Dosage

Standard Dosage

Adults:

• Multiple-dose regimen: 0.25 mg subcutaneously daily, starting on day 5 (morning or evening) or day 6 (morning) of ovarian stimulation, and continuing until human chorionic gonadotropin (hCG) administration.
• Single-dose regimen: 3 mg subcutaneously as a single dose on day 7 of ovarian stimulation (range: day 5-9). If hCG is not administered within 4 days, supplemental doses of 0.25 mg daily are given until hCG administration.

Children: Cetrorelix is not indicated for pediatric use.

Special Cases:

• Elderly Patients: No relevant use in this population.
• Patients with Renal Impairment: Contraindicated in severe renal impairment. Caution is advised in mild to moderate impairment.
• Patients with Hepatic Dysfunction: Caution is advised.
• Patients with Comorbid Conditions: No specific dosage adjustments mentioned for comorbidities like diabetes or cardiovascular disease, however, careful clinical monitoring is advised.

Clinical Use Cases

Cetrorelix’s clinical use is limited to controlled ovarian stimulation in ART. It is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.

Dosage Adjustments

Dose adjustments might be necessary for patients with moderate to severe renal or hepatic impairment, although specific recommendations are not available.

Side Effects

Common Side Effects:

• Nausea
• Headache
• Local injection site reactions (redness, bruising, itching, swelling)

Rare but Serious Side Effects:

• Ovarian hyperstimulation syndrome (OHSS)
• Severe allergic reactions (including anaphylaxis)

Long-Term Effects: No long-term adverse effects specifically associated with cetrorelix have been identified.

Adverse Drug Reactions (ADR): Anaphylactic reactions are serious ADRs requiring immediate medical attention.

Contraindications

• Hypersensitivity to cetrorelix acetate, GnRH analogs, extrinsic peptide hormones, or mannitol
• Known or suspected pregnancy
• Breastfeeding
• Severe renal impairment

Drug Interactions

No formal drug interaction studies have been performed. In vitro studies indicate that interactions with drugs metabolized by cytochrome P450 enzymes are unlikely. However, caution is warranted when co-administering with gonadotropins or medications that may induce histamine release.

Pregnancy and Breastfeeding

Cetrorelix is contraindicated in pregnancy (Pregnancy Category X) and breastfeeding.

Drug Profile Summary

• Mechanism of Action: GnRH antagonist, suppresses LH and FSH release, preventing premature ovulation.
• Side Effects: Nausea, headache, local injection site reactions, OHSS, allergic reactions.
• Contraindications: Hypersensitivity, pregnancy, breastfeeding, severe renal impairment.
• Drug Interactions: Limited data, caution with gonadotropins and histamine-releasing drugs.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: 0.25 mg daily or 3 mg single dose subcutaneously during controlled ovarian stimulation.
• Monitoring Parameters: Ovarian response (ultrasound), LH levels, signs of OHSS, allergic reactions.

Popular Combinations

Cetrorelix is commonly used in combination with gonadotropins (FSH, hMG) for controlled ovarian stimulation in ART.

Precautions

• General Precautions: Exclude pregnancy before starting treatment. Monitor for hypersensitivity reactions, particularly after the first dose.
• Specific Populations: Contraindicated in pregnancy and breastfeeding. Not indicated for pediatric or geriatric use. Caution in renal or hepatic impairment.
• Lifestyle Considerations: No specific lifestyle restrictions mentioned.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Cetrorelix?

A: 0.25 mg subcutaneously daily or a single 3 mg dose, both given during controlled ovarian stimulation. See detailed dosage guidelines above.

Q2: How does Cetrorelix differ from GnRH agonists used in IVF?

A: GnRH agonists initially cause a flare-up effect, increasing gonadotropin release before suppressing it. Cetrorelix, being an antagonist, directly suppresses gonadotropins without the initial flare-up, potentially leading to a lower risk of OHSS.

Q3: What are the signs and symptoms of OHSS that I should monitor for?

A: Mild symptoms include abdominal bloating, discomfort, and nausea. Moderate OHSS may involve vomiting, diarrhea, weight gain, and enlarged ovaries. Severe OHSS can present with significant abdominal distension, shortness of breath, decreased urination, and rapid weight gain, requiring hospitalization.

Q4: Can Cetrorelix be used in patients with kidney problems?

A: Cetrorelix is contraindicated in patients with severe renal impairment and should be used cautiously in patients with mild to moderate renal impairment.

Q5: Are there any specific drug interactions I should be aware of with Cetrorelix?

A: Formal drug interaction studies are limited. Caution should be exercised when co-administering cetrorelix with gonadotropins or medications known to induce histamine release.

Q6: Can Cetrorelix be used during pregnancy or breastfeeding?

A: No. Cetrorelix is contraindicated during pregnancy and breastfeeding.

Q7: How is Cetrorelix administered?

A: Cetrorelix is administered subcutaneously, usually into the lower abdominal wall.

Q8: What should I do if I miss a dose of Cetrorelix?

A: Contact your physician immediately for instructions if a dose is missed.

Q9: What is the mechanism of action of Cetrorelix?

A: Cetrorelix competitively binds to GnRH receptors in the pituitary, blocking the release of LH and FSH, preventing premature ovulation.

Q10: What is the storage information for Cetrorelix?

A: The medication needs to be refrigerated between 36 and 46 degrees Fahrenheit or 2 to 8 degrees Celcius. Do not freeze. Keep out of reach of children.