VA Class:HS701
ATC Class:H01CC02
Cetrorelix acetate, a synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH), is a GnRH antagonist.
Cetrorelix is used as a component of infertility regimens (recombinant FSH or human menopausal gonadotropin [hMG], cetrorelix, and human chorionic gonadotropin [hCG]) to inhibit premature LH surges in women undergoing controlled ovarian stimulation (COS).1, 2, 3, 4, 5
Efficacy of infertility therapy was established in several controlled studies,1, 2, 3, 4 which included women with normal endocrine and pelvic ultrasound parameters.3, 5 The studies excluded individuals with polycystic ovarian syndrome, those with low or no ovarian reserve, and those with stage III or IV endometriosis.1, 2 In 2 dose-finding studies, the minimal effective dosage for inhibition of premature LH surges is 3 mg of cetrorelix administered once as a single dose (single-dose regimen) or 0.25 mg administered daily until injection of hCG (multiple-dose regimen).1 Mean fertilization rates averaged 48-66% for the single-dose regimen and 59-63% for the multiple-dose regimen.1, 4 Vital pregnancy rates per attempt or per individual with embryo transfer were 23 or 26%, respectively, for the single-dose regimen and 20-22 or 23-24%, respectively, for the multiple-dose regimen.1, 2, 3, 4 Less than 2% of patients administered the single- or multiple-dose regimen experienced a premature LH surge (i.e., cetrorelix failure).1, 2, 4
Reconstitution and Administration
Cetrorelix acetate is administered by subcutaneous injection either once as a single dose or once daily in multiple smaller doses.1
Cetrorelix acetate 0.25- or 3-mg sterile powder for subcutaneous injection should be stored at 2-8 or 25°C, respectively.1
Prior to administration, cetrorelix acetate sterile powder should be reconstituted with sterile water for injection using the prefilled syringe and the 20-gauge needle provided by the manufacturer.1 The vial should be agitated gently until the powder is completely dissolved;1 care should be taken to avoid formation of bubbles.1 The manufacturer states that cetrorelix should be inspected visually prior to administration and should not be used if the solution is not clear or contains a precipitate.1, 5 For subcutaneous injection, the entire contents of the vial should be withdrawn into the syringe, and the drug should be administered using a 27-gauge needle provided by the manufacturer.1
Dosage of cetrorelix acetate is expressed in terms of cetrorelix.1, 5
The recommended dosage of cetrorelix for the inhibition of premature LH surges in adult women undergoing controlled ovarian stimulation (with human menopausal gonadotropin [hMG] or recombinant FSH) is 3 mg administered once (single-dose regimen)1, 2 or 0.25 mg administered daily (multiple-dose regimen)1, 3, 4 during the early to mid-follicular phase of the menstrual cycle.1, 2
Ovarian stimulation therapy (with FSH or hMG) usually is initiated on day 2 or 3 of the menstrual cycle.1, 2, 3, 4
In patients receiving the single-dose regimen, 3 mg of cetrorelix may be administered when the serum estradiol concentration is indicative of an appropriate stimulation response usually on stimulation day 7 (range: day 5-9).1, 2 If human chorionic gonadotropin (hCG) has not been given within 4 days of administration of the single 3-mg dose of cetrorelix, 0.25 mg of the drug should be given once daily beginning 96 hours after administration of the single 3-mg dose and continued until and including the day of hCG administration.1, 2, 5
In patients receiving the multiple-dose regimen, 0.25 mg of cetrorelix may be initiated on day 5 (morning or evening) or on the morning of day 6 of stimulation and continued daily until an adequate follicular response is achieved, at which time hCG is administered and ovarian stimulation therapy and cetrorelix are discontinued.1, 3, 4, 5
Human chorionic gonadotropin (hCG) should not be administered if the ovaries show an excessive response to the treatment with gonadotropins because of an increased risk of ovarian hyperstimulation syndrome.1 Oocyte retrieval, followed by in vitro fertilization or intracytoplasmic sperm injection, is then performed, with subsequent attempts at implantation and pregnancy.1, 2, 3, 4
Not applicable.
Known hypersensitivity to cetrorelix acetate, mannitol, or any ingredient in the formulation.1 Known hypersensitivity to extrinsic peptide hormones, GnRH, or any other GnRH analog.1 Known or suspected pregnancy or lactation.1
Cetrorelix should be prescribed by clinicians who are experienced in infertility treatment.1
Severe anaphylaxis associated with cough, rash, and hypotension has been reported in at least one patient who received cetrorelix (10 mg daily for 7 months for an indication other than infertility).1 Therefore, the manufacturer states that patients should be monitored carefully after initial injection.1
Fetal/Neonatal Morbidity and Mortality
Because of the antigonadotropic properties of cetrorelix, fetal mortality could occur if administered during pregnancy.1
Before initiating cetrorelix therapy, pregnancy must be excluded.1 Several cases of major and minor congenital anomalies were reported in women who received cetrorelix during pregnancy; 1 a causal relationship is unknown.1
Elevations in liver function test results including ALT (SGPT), AST (SGOT), γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGTP), and alkaline phosphatase up to 3 times the upper limit of normal were reported in 1-2% of patients receiving cetrorelix during controlled ovarian stimulation.1
Category X.1 (See Users Guide.) May result in fetal loss secondary to antigonadotropic properties.1 (See Cautions: Contraindications and also Warnings: Fetal/Neonatal Morbidity and Mortality.)
It is not known whether cetrorelix is distributed in milk;1 use in nursing women is not recommended.1
Not indicated.5
Not indicated for use in geriatric adults 65 years of age and older.1
Adverse effects occurring in 1% or more of patients receiving cetrorelix include ovarian hyperstimulation syndrome,1 nausea,1 and headache.1
Cetrorelix acetate, a synthetic decapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone, gonadorelin), is a GnRH antagonist.1, 2, 3, 4
Cetrorelix competitively blocks GnRH receptors on the anterior pituitary gonadotroph and the subsequent transduction pathway, inducing a rapid, reversible suppression of gonadotropin (luteinizing hormone [LH], follicle-stimulating hormone [FSH]) secretion.1, 2, 3, 4, 5 The suppression of pituitary LH secretion by cetrorelix is more pronounced than that of FSH.1 By suppressing the midcycle GnRH-induced surge in LH, cetrorelix can suppress ovulation, oocytic meiosis, and luteinization.1 In women undergoing controlled ovarian stimulation, the drug can prevent the LH surges associated with such stimulation and improve implantation and pregnancy rates associated with in vitro fertilization or intracytoplasmic sperm injection (ICSI).1, 2, 3, 4
Following subcutaneous administration of a single 3- or 0.25-mg dose of cetrorelix, the onset of action usually occurs within 1 or 2 hours, respectively, and persists for at least 4 days or 24 hours, respectively.1 Cetrorelix competitively blocks GnRH receptors on the anterior pituitary gonadotroph and the subsequent transduction pathway, inducing a rapid, reversible suppression of gonadotropin (luteinizing hormone [LH], follicle-stimulating hormone [FSH]) secretion.1, 2, 3, 4, 5 The suppression of pituitary LH secretion by cetrorelix is more pronounced than that of FSH.1 By suppressing the midcycle GnRH-induced surge in LH, cetrorelix can suppress ovulation, oocytic meiosis, and luteinization.1 In women undergoing controlled ovarian stimulation, the drug can prevent the LH surges associated with such stimulation and improve implantation and pregnancy rates associated with in vitro fertilization or intracytoplasmic sperm injection (ICSI).1, 5
Discuss duration of treatment and required monitoring procedures.1 Risks of cetrorelix administration during pregnancy;1 need for pregnancy testing prior to initiation of cetrorelix therapy.1 Risk of potential adverse effects.1 If cetrorelix is administered by the patient, provide copy of manufacturer's patient information.1
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. Is is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for subcutaneous use only | 0.25 mg (of cetrorelix) | Cetrotide® (available with prefilled disposable syringe containing 1 mL or 3 mL sterile water for injection diluent, needles, and alcohol swabs) | |
3 mg (of cetrorelix) | Cetrotide® (available with prefilled disposable syringe containing 1 mL or 3 mL sterile water for injection diluent, needles, and alcohol swabs) | Serono |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions January 1, 2004. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Serono, Inc. Cetrotide® (cetrorelix acetate) for injection prescribing information. Randolph, MA; 2000 Aug.
2. Olivennes F, Belaisch-Allart J, Emperaire JC et al. Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin). Fertil Steril . 2000; 73:314-20. [PubMed 10685535]
3. Albano C, Felberbaum RE, Smitz J et al. Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. Hum Reprod . 2000; 15:526-31. [PubMed 10686191]
4. Felberbaum RE, Albano C, Ludwig M et al. Ovarian stimulation for assisted reproduction with HMG and concomitant midcycle administration of the GnRH antagonist cetrorelix according to the multiple dose protocol: a prospective uncontrolled phase III study. Hum Reprod . 2000; 15:1015-20. [PubMed 10783344]
5. Serono Laboratories, Inc., Norwell, MA: Personal communication.