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Cetrorelix
Indications, Uses, Dosage, Drugs Interactions, Side effects
Cetrorelix
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Gonadotropin-releasing hormone (GnRH) antagonists, Therapy Class:
Synthetic hormone, Approved Countries
The United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Cetrorelix is a synthetic hormone belonging to the pharmacological class of Gonadotropin-releasing hormone (GnRH) antagonists.
The FDA has approved Cetrorelix for the treatment of hormone-related disorders; mainly, it is used in assisted reproductive technology to stop adults receiving controlled ovarian stimulation during fertility treatment procedures from experiencing early surges of luteinizing hormone.
Cetrorelix rapidly absorbs with an 85% bioavailability, reaching peak plasma levels within 1-2 hours. It has a distribution volume of around 1 L/kg, 86% plasma protein binding, and undergoes peptidase-mediated metabolism. Elimination occurs via faeces (5-10%) and urine (2-4%), with a 30-hour half-life.
The most common side effects of Cetrorelix include injection site reaction (redness, itching, and irritation), nausea and vomiting.
Cetrorelix is available in the form of injectable solutions.
The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Cetrorelix is a synthetic hormone belonging to the pharmacological class of Gonadotropin-releasing hormone (GnRH) antagonists.
Gonadotropin-releasing hormone (GnRH) analogue Cetrorelix is a synthetic analogue of gonadorelin that binds to anterior pituitary receptors competitively with naturally occurring GnRH. This suppresses luteinization, oocytic meiosis, and ovulation by delaying the premature luteinizing hormone (LH) surge.
The half-life spans from 20 to 63 hours, with an onset within 12 hours and peak plasma times at 1 hour for a 0.25mg dose and 1.5 hours for a 3mg dose.
Cetrorelix is available in the form of injectable solutions.
Injectable solutions: Cetrorelix 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.
Cetrorelix is used to treat female infertility during fertility treatments by preventing premature luteinizing hormone surges and aiding controlled ovarian stimulation.
In Female infertility
Cetrorelix, a hormone antagonist, impedes premature ovulation, ensuring suitable egg development in the ovary, thereby increasing the probability of conception and successful pregnancy in women undergoing fertility treatments, marking a crucial advancement in assisted reproductive therapies for addressing infertility concerns. Administered via injection by healthcare professionals, it promotes normal egg maturation, enhancing fertility and the likelihood of successful pregnancy, cautioning against self-administration.
It is recommended for women undergoing controlled ovarian stimulation, oocyte pick-up, and assisted reproductive procedures in order to prevent premature LH surges.
Parenterally: Cetrorelix is administered via subcutaneous injection into the lower abdominal wall once a day. To mitigate injection site reactions, rotating sites, delaying injections at the same spot, and administering the medication slowly aid in gradual absorption.
Administration in the morning
Cetrorelix treatment often starts around day 5 or 6 of ovarian stimulation (about 96 to 120 hours after initiation) with gonadotropins. It continues during the treatment period, adjusted based on ovarian response. If follicular growth is lacking, initiation may be delayed.
Administration in the evening
Cetrorelix treatment typically commences on day 5 (around 96 to 108 hours post-stimulation initiation), continuing until the evening before ovulation induction, contingent upon ovarian response and follicular growth. Delayed initiation may occur due to inadequate follicular growth, although usual practice starts Cetrorelix on day 5 or 6 of stimulation.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Injectable solutions: 0.25mg, 3mg
Cetrorelix is available in the form of injectable solutions.
Dose Adjustment in Adult Patients:
Infertility Treatment
When serum estradiol levels exhibit the proper stimulation response (range days 5-9), a single dosage regimen of 3 mg SC is administered. Usually, on day 7, if hCG is not given within four days, the daily dosage of 0.25 mg is continued until hCG is administered.
Multiple dosage regimen: 0.25 mg SC in the morning, evening, or morning of day five or day six stimulation; continue until hCG is delivered.
While using Cetrorelix, eliminate fried and processed foods. Consume high-fat dairy, like whole milk, over low-fat options. Incorporate fibre-rich foods—whole grains, fruits, and vegetables—into your diet. Refrain from high-sugar refined carbohydrates. Substitute animal proteins (eggs, fish, and meat) with plant-based sources like nuts, seeds, and beans. 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.
Cetrorelix may be contraindicated in the following conditions:-
- Hypersensitivity to cetrorelix, extrinsic peptide hormones or mannitol.
- Known hypersensitivity to GnRH or any other GnRH analogs.
- Known or suspected pregnancy and lactation.
- Severe renal impairment
Warnings
Physicians with expertise in fertility treatment should be responsible for prescribing Cetrorelix. Before beginning Cetrorelix medication, pregnancy needs to be ruled out.
Precautions
Post-marketing surveillance reports of hypersensitivity events have been made, including anaphylactoid reactions with the initial dose.
During seven months of treatment with Cetrorelix (10 mg/day), a severe anaphylactic reaction accompanied by cough, rash, and hypotension was noted in one patient in a study for an indication unrelated to infertility.
Women who exhibit symptoms of current allergy disorders or have a history of recognized allergies should receive special attention. For women with severe allergy problems, treatment with Cetrorelix is not recommended.
Alcohol Warning
It is unsafe to consume Cetrorelix with alcohol.
Breast Feeding Warning
It is not recommended for use during breastfeeding.
Pregnancy Warning
It is unsafe to use during pregnancy.
Food Warning
Avoid fried foods, choose whole dairy, and limit alcohol intake.
The adverse reactions related to Cetrorelix can be categorized as
- Common Adverse Effects: Injection site reactions, headaches, and abdominal discomfort or pain.
- Less Common Adverse Effects: Ovarian hyperstimulation syndrome, hepatic enzyme elevation, nausea.
- Rare Adverse Effects: Erythema at injection site, itching, pruritus, swelling, redness, hypotension, rash, and coughing.
Cetrorelix lacks formal drug interaction studies. In vitro assessments suggest minimal interactions with drugs metabolized by cytochrome P450 or glucuronidation. Yet, potential interactions with gonadotropins or agents inducing histamine release in sensitive individuals remain uncertain.
The common side effects of Cetrorelix include:-
- Nausea
- Syndrome of ovarian hyperstimulation
- Itching
- Irritation
- Vomiting
- Lower abdominal pain
- Itching, redness, or swelling at the site of injection
- Headache
- Pregnancy
Pregnancy Category X (FDA): When pregnant, avoid using. The risks outweigh the potential benefits. There are safer alternatives available.
It is not indicated for pregnant women.
Animal data
In rat experiments, cetrorelix acetate did not affect implanted conceptus development during the first seven days of pregnancy at dosages up to 38 µg/kg, which is approximately one of the recommended therapeutic doses for humans based on body surface area. However, total resorption was achieved at 139 µg/kg, or almost four times the human dose. Doses of 4.6 µg/kg (0.2 times the human dose) in rats and 6.8 µg/kg (0.4 times the human dose) in rabbits given to pregnant rats and rabbits from day 6 until near term resulted in early resorptions and total implantation losses. Although there was no rise in fetal abnormalities in maintained pregnancies, pregnant women should avoid Cetrotide® since it may cause fetal loss in humans due to fetal resorption brought on by changes in hormone levels.
Fertility
Research on animal fertility has revealed that cetrorelix affects pregnancy, reproductive function, and fertility in a dose-related approach. When the medication was given during the vulnerable stage of pregnancy, there were no teratogenic consequences.
- Nursing Mothers
It is unknown if human milk contains Cetrorelix secreted in it. Nursing mothers should not use Cetrorelix because it has not been determined how it would affect lactation or the breastfed infant, as many medications are excreted in human milk.
- Pediatric Use
As per the FDA, Cetrorelix is not intended for use in this population.
- Geriatric Use
As per the FDA, Cetrorelix is not intended for subjects aged 65 and over.
Dose Adjustment in Kidney Impairment Patients:
Mild-to-moderate impairment: Dose adjustment not described by the manufacturer
Severe renal impairment: Contraindicated
Dose Adjustment in Hepatic Impairment Patients:
Hepatic impairment: No dosage adjustment is required.
In humans, no over-dosage incidents have been reported with Cetrorelix doses of 0.25 mg or 3 mg. Patients receiving single doses up to 120 mg for alternate indications showed good tolerance without indications of over-dosage.
There is no specific antidote or treatment for excessive Cetrorelix intake, so treatment typically involves symptomatic and supportive measures. Continuous observation and appropriate medical interventions are recommended to address particular symptoms or complications.
Pharmacodynamics:
GnRH stimulates the anterior pituitary's gonadotrophic cells to produce and release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH liberation is increased at midcycle due to positive estradiol (E2) feedback, which causes an LH jump. As seen by growing progesterone levels, this LH surge triggers the dominant follicle to ovulate, restarting oocyte meiosis and, ultimately, luteinization. The release of LH and FSH is dose-dependently regulated by cetrorelix, which binds to pituitary cell membrane receptors in competition with endogenous GnRH.
Pharmacokinetics:
Absorption
Upon subcutaneous administration, Cetrorelix rapidly absorbs, exhibiting an approximate bioavailability of 85% and reaching peak plasma concentration within 1-2 hours.
Distribution
Its distribution encompasses a volume of approximately 1.2 liters per kilogram and exhibits a high plasma protein binding of 86%.
Vd: 1.2 L/kg
Metabolism
Metabolism primarily involves peptidases, leading to the predominant formation of (1-4), (1-9), (1-7), and (1-6) peptides.
Elimination
Elimination involves faeces (5-10% as an unchanged drug and its metabolites) and urine (2-4% as an unchanged drug). The terminal elimination half-life extends to approximately 30 hours, indicating a more prolonged duration within the body before clearance.
- Mettler L, Brandenburg K. Cetrotide confirmatory trial of cetrorelix/0.25 mg in 26 women undergoing ovarian stimulation with recombinant follicle stimulating hormones for IVF, ICSI and embryo transfer (ET). Clin Exp Obstet Gynecol. 2000;27(2):103-5. PMID: 10968345.
- Wilcox J, Potter D, Moore M, Ferrande L, Kelly E; CAP IV Investigator Group. Prospective, randomized trial comparing cetrorelix acetate and ganirelix acetate in a programmed, flexible protocol for premature luteinizing hormone surge prevention in assisted reproductive technologies. Fertil Steril. 2005 Jul;84(1):108-17. doi: 10.1016/j.fertnstert.2005.03.016. PMID: 16009165.
- Lee TH, Lin YH, Seow KM, Hwang JL, Tzeng CR, Yang YS. Effectiveness of cetrorelix for the prevention of premature luteinizing hormone surge during controlled ovarian stimulation using letrozole and gonadotropins: a randomized trial. Fertil Steril. 2008 Jul;90(1):113-20. doi: 10.1016/j.fertnstert.2007.06.029. Epub 2007 Dec 11. PMID: 18054932.
- Olivennes F, Diedrich K, Frydman R, Felberbaum RE, Howles CM; Cerotide Multiple Dose International Study Group; Cetrotide Single Dose International Study Group. Safety and efficacy of a 3 mg dose of the GnRH antagonist cetrorelix in preventing premature LH surges: report of two large multicentre, multinational, phase IIIb clinical experiences. Reprod Biomed Online. 2003 Jun;6(4):432-8. doi: 10.1016/s1472-6483(10)62163-3. PMID: 12831588.
- US Food and Drug Administration (FDA) [Internet]. Maryland. USA; Package leaflet information for the user; Cetrotide® (cetrorelix acetate for injection)
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021197s010lbl.pdf
- https://www.ema.europa.eu/en/documents/product-information/
- KD Tripathi. [link]. Seventh Edition. New Delhi, India: Jaypee Brothers Medical Publishers; 2013: Page No 243
Dr. Chumbeni E Lotha has completed her Bachelor of Pharmacy from RIPANS, Mizoram and Doctor of Pharmacy from SGRRU,Dehradun. She can be reached at editorial@medicaldialogues.in
Dr JUHI SINGLA has completed her MBBS from Era’s Lucknow Medical college and done MD pharmacology from SGT UNIVERSITY Gurgaon. She can be contacted at editorial@medicaldialogues.in. Contact no. 011-43720751
Published on: 29 Nov 2023 4:34 AM GMT