cetrorelix
Sources réglementaires consultées
Indications approuvées
- Prévention de l’ovulation prématurée pendant une stimulation ovarienne contrôlée suivie du prélèvement d’ovocytes et de techniques de procréation médicalement assistée.
Contre-indications
Absolues
- Hypersensibilité au cétrorélix, aux analogues de la GnRH, aux hormones peptidiques exogènes ou aux excipients.
- Insuffisance rénale sévère.
- Grossesse ou allaitement.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer des réactions allergiques ou pseudo-allergiques, y compris une anaphylaxie mortelle, dès la première dose ; un traitement d’urgence doit être immédiatement disponible. — CIMA/AEMPS, ficha técnica 85838
- Mise en garde majeure · Surveiller le syndrome d’hyperstimulation ovarienne pendant et après la stimulation. — CIMA/AEMPS, ficha técnica 85838
Interactions médicamenteuses
- ModéréeMédicaments libérant de l’histamine
Mécanisme: Une interaction chez les personnes sensibles ne peut être exclue.
Recommandation: Maintenir une surveillance clinique et disposer d’un traitement d’urgence.
CIMA/AEMPS, ficha técnica 85838
Effets indésirables
Communs (≥1%)
Érythème, gonflement et prurit transitoires au site d’injection
Rares mais graves
Anaphylaxie et syndrome d’hyperstimulation ovarienne sévère
Grossesse et allaitement
Contre-indiqué pendant la grossesse et l’allaitement.
Bibliographie récente (PubMed)
Uterine fibroids are the most common pelvic tumors in women, representing the primary indication of hysterectomy. Gonadotropin-releasing hormone (GnRH) antagonists represent a new therapeutic option for premenopausal women. The aim of this review is to evaluate the efficacy and safety of GnRH antagonists in the treatment of uterine fibroids (size reduction and symptom control). A review of studies from electronic databases (PubMed and Cochrane Central) published up to December 2023 was performed. Eleven randomized clinical trials with a total of 4164 patients were included in the review, which evaluated GnRH antagonists (Relugolix, Elagolix, Linzagolix and Cetrorelix) against placebo or GnRH agonists in premenopausal women with uterine fibroids and heavy menstrual bleeding. The results of the measures evaluated to determine the efficacy and safety of GnRH antagonists versus placebo are favorable for the variables of control of uterine bleeding (Relative risk (RR) = 5.09; 95% CI 3.19 to 8.14), percentage reduction of fibroid volume (Mean difference (MD) = -27.36; 95% CI -38.89 to -15.83) and lower reduction of bone density (MD -0.35; 95% CI -0.47 to -0.24). The results do not allow us to conclude whether there are differences between the alternatives compared in the control of vasomotor symptoms. GnRH antagonists represent an effective alternative for uterine fibroids treatment as they allow a superior reduction in menstrual bleeding and uterine fibroid volume compared to the placebo group.
Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists' clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases.
Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Both approaches are efficient but incompatible with pregnancy planning. Therefore, there is a call for medical practice to develop therapeutical means of preventing leiomyoma onset in patients planning on becoming pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, in meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeutic treatments of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, or DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2, and FH genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.
To compare the effect of Medroxyprogesterone acetate versus Gonadotropin releasing hormone antagonist for the prevention of premature luteinizing hormone (LH) surge in infertile hyper-responder women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) cycles. One hundred infertile hyper-responder women who were candidate for IVF/ICSI were randomly assigned into two groups. Group 1 was given 20 mg Medroxyprogesterone acetate from day 1 of the menstrual cycle till trigger day. Group 2 was given GnRH antagonist (injection Cetrorelix 0.25 mg s/c) from the day when the leading follicle reached 14 mm until the day of trigger for the prevention of premature LH surge (flexible protocol). We measured LH serum levels on day 1, day 7 of cycle and on trigger day. The primary outcome measured was the incidence of premature LH surge. Other outcome measures were total number of mature follicles on trigger day, total number of mature oocytes retrieved and number of good quality day-3 embryos. There was no premature luteinizing hormone surge in both groups of our study. The mean number of follicles on trigger day, mean number of M2 oocytes retrieved and mean number of good quality day-3 embryos were comparable in both the groups, with no statistically significant difference. The results of this study stated that MPA can be an effective alternative to GnRH antagonist for the prevention of premature LH surge in hyper-responder women undergoing COS for IVF. It is easy to use, widely available and cost-effective. It may establish a new regimen of ovarian stimulation using MPA as an oral alternative to GnRH antagonist treatment in hyper-responders.
This study aimed to conduct computer searches in PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP, Wanfang, and CBM databases. Literature was screened and data extracted according to the inclusion and exclusion criteria. RevMan 5.3 was used to assess the methodological quality of the included studies, while Stata 14.0 was employed to rank the efficacy and safety of the five interventions. This analysis included 20 randomised controlled trials involving a total of 2,400 patients. The cumulative probability ranking results showed that, for improving clinical pregnancy rate (CPR), leuprorelin (97.8%) ranked highest, followed by cetrorelix (70.7%), triptorelin (47.9%), buserelin (18.2%), and ganirelix (15.3%). For improving the live birth rate (LBR), leuprorelin (99.9%) ranked highest, followed by triptorelin (44.1%) and cetrorelix (5.9%). For reducing the incidence of ovarian hyperstimulation syndrome (OHSS), cetrorelix (96.9%) ranked highest, followed by buserelin (58.7%), ganirelix (57.5%), leuprorelin (21.2%), and triptorelin (15.7%). Cetrorelix demonstrated superior performance in reducing the risk of OHSS, while leuprorelin was more effective in improving CPR and LBR. For women with polycystic ovary syndrome at high risk of OHSS, cetrorelix is recommended. For patients with the primary goal of improving CPR or LBR, leuprorelin is the more appropriate choice. Key Words: Polycystic ovary syndrome, Infertility, GnRH agonist, GnRH antagonist, Assisted reproduction.