Cetrorelix (Monograph)

Brand name: Cetrotide
Drug class: Antigonadotropins
- Gonadotropin-releasing Hormone Antagonists
- GnRH Antagonists
ATC class: H01CC02
VA class: HS701
Chemical name: N-Acetyl-3-(2-naphthalenyl)-d-alanyl-4-chloro-d-phenylalanyl-3-(3-pyridinyl)-d-alanyl-l-seryl-l-tyrosyl-N5-(aminocarbonyl-d-ornithyl-l-leucyl-l-arginyl-l-prolyl acetate (salt)
Molecular formula: C₇₀H₉₂ClN₁₇O₁₄•C₂H₄O₂
CAS number: 145672-81-7

Medically reviewed by Drugs.com on Oct 6, 2023. Written by ASHP.

Introduction

Gonadotropin-releasing hormone (GnRH) antagonist; a synthetic decapeptide analog of naturally occurring GnRH.

Uses for Cetrorelix

Female Infertility

Used as a component of controlled ovarian stimulation regimens (e.g., recombinant FSH or human menopausal gonadotropin [hMG], and human chorionic gonadotropin [hCG]) to delay premature LH surges and consequently ovulation during assisted reproductive technologies (ART) programs.

Cetrorelix Dosage and Administration

General

• Should be prescribed by clinicians experienced in infertility treatment.

• Prior to use of cetrorelix, initiate controlled ovarian stimulation (COS) therapy with gonadotropins (FSH or hMG) usually on day 2 or 3 of the menstrual cycle. Individualize dosage of gonadotropins based on the patient’s ovarian response to allow sufficient follicular development.

• Initiate therapy with cetrorelix on days 5–7 of COS therapy and continue COS therapy until sufficient follicular growth is verified (e.g., ultrasound).

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

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

Administration

Sub-Q Administration

Administer by sub-Q injection either once as a single dose or once daily in multiple smaller doses in early- to mid-follicular phase of the menstrual cycle.

For the single-dose regimen, administer by sub-Q injection once on the day of COS when the serum estradiol concentration is indicative of an appropriate stimulation response (400 pg/mL), usually on stimulation day 7 (range: day 5–9).

For the multiple-dose regimen, administer by sub-Q injection on day 5 (morning or evening) or on the morning of day 6 of COS and continue daily until an adequate follicular response is achieved.

Administer using 27-gauge needle (provided by manufacturer) into lower abdominal area, preferably around, but ≥2.54 cm (1 inch) from the umbilicus. With multiple doses, rotate injection sites to minimize local irritation.

Reconstitution

Reconstitute vial containing 0.25 or 3 mg of cetrorelix acetate sterile lyophilized powder with 1 or 3 mL, respectively, of sterile water for injection using the prefilled syringe and 20-gauge needle (provided by manufacturer).

Gently agitate vial until powder is completely dissolved; avoid formation of bubbles. Withdraw entire contents of the vial into the syringe, then replace 20-gauge needle with 27-gauge needle (provided by manufacturer) for administration.

Reconstituted solutions contain no preservatives; prepare solutions immediately before use.

Dosage

Available as cetrorelix acetate; dosage expressed in terms of cetrorelix.

Adults

Female Infertility

Single-dose Regimen

Sub-Q

3 mg once as a single dose in combination with COS therapy; initiate usually on day 7 of COS therapy (range: day 5–9). (See General and also Administration, under Dosage and Administration.)

If hCG is not administered within 4 days of initial cetrorelix injection (i.e., insufficient follicular maturation), administer supplemental cetrorelix dosage of 0.25 mg once daily; initiate 96 hours after first injection and continue until and including the day of hCG administration. (See Duration under Pharmacokinetics.)

Multiple-dose Regimen

Sub-Q

0.25 mg once daily in combination with COS therapy; initiate on day 5 (morning or evening) or on the morning of day 6 of COS therapy. Continue until an adequate follicular response to stimulation therapy is achieved; a median duration of 5 days was required in clinical trials. (See General under Dosage and Administration.)

Cautions for Cetrorelix

Contraindications

• Known hypersensitivity to cetrorelix acetate, mannitol, or any ingredient in the formulation.

• Known hypersensitivity to extrinsic peptide hormones, GnRH, or any other GnRH analog.

• Severe renal impairment.

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

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryolethality reported in animals. Congenital anomalies reported in women who received cetrorelix during pregnancy.

Exclude pregnancy prior to initiation of therapy.

Sensitivity Reactions

Severe anaphylaxis associated with cough, rash, and hypotension during therapy exceeding recommended dosages (10 mg daily for 7 months for an indication other than infertility) reported. Monitor patients carefully after initial injection. Take special care in women with signs and symptoms of active allergic conditions or history of allergies. Use not recommended in women with severe allergic conditions.

General Precautions

Hepatic Effects

Elevations in liver function test results including ALT, AST, γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGTP), and alkaline phosphatase reported.

Specific Populations

Pregnancy

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

Lactation

Not known whether cetrorelix is distributed into milk. Use not recommended.

Pediatric Use

Not intended for use in pediatric patients.

Geriatric Use

Not intended for use in patients ≥65 years of age.

Common Adverse Effects

Ovarian hyperstimulation syndrome, nausea, headache.

Drug Interactions

No formal drug interaction studies to date.

Cetrorelix Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability in healthy females is 85%.

Onset

Single 3-mg dose: Suppression of LH secretion within 1 hour.

Single 0.25-mg dose: Suppression of LH secretion within 2 hours.

Duration

Single 3-mg dose: LH secretion suppressed for ≥4 days.

Single 0.25-mg dose: LH secretion suppressed for 24 hours.

Distribution

Extent

Distributes into follicular fluid; similar concentrations in follicular fluid and plasma on day of oocyte retrieval.

Not known whether cetrorelix is distributed into milk.

Plasma Protein Binding

86%.

Elimination

Metabolism

Metabolized by peptidases to smaller peptides.

Elimination Route

In 24 hours, excreted in urine as unchanged drug (2–4%) and in bile (5–10%) as unchanged drug and metabolites.

Half-life

Single 0.25-mg dose: 5 hours.

Multiple 0.25-mg doses: 20.6 hours.

Single 3-mg dose: 62.8 hours.

Stability

Storage

Parenteral

Powder for Injection

0.25-mg vial: 2–8°C; store vials in carton to protect from light until used.

3-mg vial: 25°C (may be exposed to 15–30°C); protect from excessive moisture and heat. Store vials in carton to protect from light until used.

Actions

• Competitively blocks GnRH receptors on the anterior pituitary and induces a rapid, reversible suppression of LH and FSH secretion.

• Prevents the LH surges associated with COS therapy with gonadotropins. By delaying premature ovulation, oocytic meiosis, and luteinization, sufficient follicular growth is more likely to occur with such stimulation therapy.

• Improves implantation and pregnancy rates associated with ART programs.

Advice to Patients

• Importance of providing patient a copy of manufacturer’s patient information.

• Importance of informing clinicians of a history of severe allergic reactions prior to initiation of therapy.

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

• Importance of contacting a clinician immediately if prescribed dosage is exceeded.

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

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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